Improvement of Outcomes in Draf III/Endoscopic Modified Lothrop Procedure

Chronic rhinosinusitis (CRS) is an inflammatory disorder affecting the sinonasal mucosa.
Chronic symptoms include facial pain and pressure, nasal airway obstruction, anosmia and
nasal discharge (sometimes purulent), in addition to significant effects on overall quality
of life. The cost of CRS is estimated to be approximately $4 billion per year and results in
over 20 million physician visits per year. The frontal sinuses are paired paranasal sinuses
housed superiorly and anteriorly in the frontal bone on each side, separated by an
inter-sinus septum which is contiguous with the nasal septum. The frontal sinuses, like the
other paranasal sinuses, can be affected in chronic rhinosinusitis, with inflammation of the
frontal sinus outflow tract causing obstruction and subsequent symptoms. First line therapy
involves medical therapy often with combination of antibiotics, nasal saline irrigation,
topical and/or systemic corticosteroids, with endoscopic sinus surgical therapy reserved for
patients with persistent symptoms after medical therapy.

Surgical therapy of the frontal sinus is the most technically demanding aspect of endoscopic
sinus surgery, and due to this, surgical dissection of the frontal sinuses has been
discouraged in the past. Otolaryngology textbooks also emphasize that chronic frontal sinus
disease may be related to unnecessary instrumentation of the frontal recess. With recent
advances in endoscopic sinus surgery and the advent of balloon sinusotomy, the rate of
frontal sinus surgery has more than doubled from 2000 to 2009.

Primary frontal sinus surgery can be approached with balloon dilation or by endoscopic
sinusotomy. Endoscopic sinusotomy of the frontal sinus involves increasing the size of the
frontal recess with anterior ethmoidectomy and removal of the agger nasi cell anteriorly, and
any frontal cells that may be present. Frontal sinus surgery is effective, as evidenced by a
recent study analyzing long-term results after primary frontal sinus surgery showing a
patency rate of 92% in a nearly 2-year average follow up period.

Refractory frontal sinusitis can be addressed surgically through external or 'extended'
endonasal approaches. Historically, external approaches were first utilized, with
introduction of osteoplastic flap techniques by Brieger in the 1890s. Lothrop introduced the
Lothrop Procedure in 1914 which required an osteoplastic flap with removal of the frontal
sinus floor and intersinus septum along with the upper aspect of the nasal septum to create a
unified drainage pathway for the frontal sinuses. In the 1950s, Montgomery popularized the
frontal sinus obliteration through osteoplastic flap approach leaving the frontal sinuses
permanently non-functional through obliteration with fat or other materials. Though these
external approaches often had high success rates, they require extensive dissection and are
associated with a high morbidity and complication rate upwards of 20%. These complications
included dural exposure, dural laceration with cerebrospinal fluid leak, orbital injury,
forehead numbness, osteomyelitis and mucocele formation.

In 1991, Wolfgang Draf described an endoscopic approach to create a common drainage pathway
akin to the Lothrop procedure which is now called the Endoscopic Modified Lothrop (EMLP) or
Draf III procedure. Currently, the EMLP provides an endoscopic alternative for persistent
frontal sinus disease after initial frontal sinusotomy, prior to consideration of frontal
sinus obliteration through an osteoplastic flap approach. The EMLP involves drilling out the
frontal sinus ostia on both sides and combining them through a superior septectomy, creating
a large common drainage pathway for the two frontal sinuses. The EMLP offers reduced
morbidity, shorter hospital stay, improved cosmetics, reduced blood loss and preservation of
a functional frontal sinus. One meta-analysis study of 18 observational studies showed a
restenosis rate of 19% and an overall failure rate of 13.9% (with failure defined as
requiring revision surgery), with failure rates ranging from 0-33%. Restenosis of the frontal
sinus ostium after EMLP is often attributed to a combination of scarring, adhesions or
neo-osteogenesis, which occurs secondary to exposed bone after the surgical procedure. The
exposed osteitic bone is believed to act as a source for inflammation and osteoblastic
activity. Persistent mucosal disease has also been postulated as a contributor to
postoperative stenosis after EMLP. Prevention of restenosis has been attempted with use of
stents or medical therapy with topical application of mitomycin C and steroids with variable
results.

Recent studies have attempted to address this issue by using mucosal grafts to cover the
exposed frontal bone after EMLP. These studies describe using free or pedicled mucosal grafts
from various sites in the nasal cavity to cover the bare bone exposed after EMLP drill out
procedure. Two studies reported results using free mucosal grafts to cover the exposed bone
and showed encouraging results, with patency rates 95% and 100%. Another study using a
pedicled flap based off the anterior ethmoidal artery showed no restenosis in 4 patients.
These studies utilize mucosa mostly from the nasal septum at the region of the superior
septectomy which would otherwise be discarded, but they do also report use of inferior
turbinate mucosa harvesting. Though minimal morbidity related to mucosal harvest was
reported, any mucosal harvest from sites other than the operative site has the potential for
creating additional postoperative morbidity. In addition, use of mucosa from a diseased
mucosal cavity may not be optimal. Reducing rates of restenosis and failure in EMLP will
allow for improved outcomes following this procedure and may prevent progression to more
invasive and extensive surgical procedures.

This study will utilize a proprietary porcine intestinal submucosa graft Cook Biodesign™ ENT
Repair graft to cover the exposed bone on the nasofrontal beak region following EMLP in order
to evaluate its effects on mucosal healing and reduction of restenosis rates of the
surgically augmented frontal sinus ostium after the Endoscopic Modified Lothrop Procedure.
The Cook Biodesign™ ENT Repair for nasal mucosal replacement has been in use for sinonasal
surgery since its Food and Drug Administration (FDA) approval in 2013. The Cook Biodesign™
ENT Repair graft is FDA approved for prescription use to "separate tissue or structures
compromised by surgical trauma, help control minimal bleeding, and act as an adjunct to aid
in the natural healing process. The device is indicated for use where an open wound dressing
material is required in the nasal and/or sinus cavities following nasal and/or sinus surgery
where separation of tissues or structures is desired."

The use of xenograft material in the method proposed in this submission has not been studied
extensively. However, using free mucosal grafts or pedicled mucosal flaps after EMLP as
previously discussed, have shown promise. The Cook Biodesign™ has been used preliminarily
with patients in this proposed setting with good anecdotal results, including reduced
crusting and good postoperative outcomes, however, its use has not yet been formally
evaluated. The Cook Biodesign™ graft has several advantages over using native mucosal grafts:
it is readily available and does not require harvest thus reducing operative times and
potential morbidity from mucosa harvest sites, it is thinner than sinus mucosa and handled
with ease, and it has tissue characteristics that promote wound healing. With the Cook
Biodesign™, our hypothesis is that its use after EMLP surgery will allow for reduction of
exposed bone in the sinonasal cavity and thus reduce inflammation, crusting and ultimately
reduce restenosis and failure rates. Additionally, we hypothesize that reduction of crusting
and inflammation will lead to improved patient reported symptom and quality of life scores on
the Sinonasal Outcomes Test-22 (SNOT-22) questionnaire.

Inclusion Criteria:

- Any patient older than 18 years of age

- Frontal sinusitis refractory to previous surgical and/or medical therapy

- Patient with skull base neoplasm which requires Draf III or Endoscopic Modified
Lothrop for exposure in excision of tumor

Exclusion Criteria:

- Previous Draf III or Endoscopic Modified Lothrop Procedure

- Allergy or objection to use of porcine-based graft material