Key-words:
Adenoma - cerebrospinal fluid leak - free mucosal graft - nonfunctioning
Introduction
Endoscopic endonasal transsphenoidal surgery (EEA) is the most commonly used approach
for the treatment of nonfunctioning pituitary adenomas (NFPA), having overcome in
recent years to the same approach, but performed under a microscope.[[1]] One of the biggest concerns that this surgery has generated is cerebrospinal fluid
(CSF) leaks, which in different publications we have found to be as high as 10%.[[2]],[[3]],[[4]] The great revolution in endoscopic skull base endoscopic reconstruction would occur
in 2006, with the description of the nasoseptal pedicled flap described by Hadad and
Bassagasteguy,[[5]] dramatically decreasing CSF fistulas in subsequent series to 0%–2.9%.[[6]],[[7]]
After a phase of the development and use of pedicled flaps, the important morbidity
that they produce at the nasal level in the area of obtaining the flap has been observed:
as we leave a large surface of the bare mucosa septum, reepithelialization is very
difficult, causing scabs, synechiae, nasal discomfort, and even perforations of the
nasal septum.[[8]],[[9]]
Although there are congress communications[[10]] and publications regarding the reconstruction of the cranial base with mucosa-free
flaps,[[8]],[[11]],[[12]] our work has the peculiarity that it is a homogeneous series, since all cases have
the same diagnosis and have been operated by the same surgical team, under the endoscopic
route, and hence, it can be useful for neurosurgeons who start in endonasal endoscopy
of the skull base.
Methods
We analyzed a series of 100 NFPA surgeries, operated with an EEA. The study was approved
by the Bioethics Committee of the Hospital where the patients were treated, and all
the patients had given their informed consent for participation in this research study
fourteen cases were analyzed prospectively and 86 retrospectively; all of them were
operated by the same surgical team, following the same indications, and using the
same procedure and protocol in all of them.
Adult patients (≥18 years) were included with the diagnosis of suspected NFPA who
met at least one of the following criteria: neurological symptomatology, hormonal
deficit, adenomas that contacted the optic pathway, or adenomas in which after deciding
an expectant treatment, tumor growth was observed during follow-up.
In addition to the epidemiological and follow-up data, the history of previous sinus
or sellar surgery or pituitary radiotherapy was studied. All patients underwent magnetic
resonance imaging, including 2 mm axial, coronal, and sagittal cuts, in 1.5 or 3T
machines. Data obtained preoperatively and postsurgical control between 3 and 6 months
were compared. The volume of the lesion was studied at both times (measured in ml
with the Brainlab Smartbrush software, except for some initial cases that were done
with Slicer 3D,[[13]]) which allowed to accurately measure the degree of resection, which for analysis
purposes was divided into gross total resection (100% resection), near-total resection
(>95%), subtotal (70%–95%), and partial (<70%). We also measured the maximum size
of the lesion in mm, the existence of suprasellar expansion or invasion of the clivus,
the degree of invasion of the cavernous sinus through the classification of Knosp,[[14]] and the presence of some nodule in its growth pattern, which could be directed
towards frontal or temporal lobes, posterior fossa or third ventricle.
Surgical intervention
Surgical interventions were performed following these principles in all cases:
-
Three/four hands technique by two surgeons, always with the collaboration of ear,
nose, and throat
-
Use of neuronavigation in reinterventions
-
Right middle turbinectomy (occasionally dislocation of the middle turbinate), wide
bilateral sphenoidotomy, and removal of 0.5–1 cm from the posterior nasal septum
-
Removal of the sellar bone in all cases, including the bone on cavernous sinuses for
expanded coronal approaches, and sellar tuberculum/sphenoid planum in the sagittal
expanded, depending on the area of tumor extension
-
Use of intraoperative Doppler to identify carotid arteries and important vessels when
necessary
-
Performance of nasoseptal pedicled flap if we anticipated a high risk of intraoperative
CSF leak. If it had not been done, it was reconstructed with middle turbinate mucosal
free mucosal graft ± fat and/or collagen matrix [[Figure 1]]. A spray sealant was almost always included as the last closure layer
-
Placement of two silicone sheets in nostrils that were removed 2 weeks after the surgery
-
The patient is recommended to perform nasal washes with physiological saline serum
and maintain a relative rest for 4 weeks, avoiding sports, efforts, and blowing his
nose. Patients with nocturnal continuous positive airway pressure (CPAP) will also
be interrupted for 2–4 weeks
-
We analyzed the existence or not of intraoperative CSF leak, extension of the performed
approach, and cranial base reconstruction technique (fat, pedicle flap, free flap,
collagen matrix, sealant).
Figure 1: Grouping of cases by treatment groups applied in relation to the maximum tumor dimension,
tumor volume and degree of resection. We see that the three groups collect cases of
similar characteristics
The results were analyzed using the statistical package Stata version 14 (StataCorp.
2015. Stata Statistical Software: Release 14. College Station, TX, USA: StataCorp
LP). Statistical significance was determined as P < 0.05.
Results
Of the 100 patients included, this was the distribution of the closure technique:
-
No mucous reconstruction: Thirteen percent. Most of them correspond to the first cases
of the series, before the implantation of the nasosoptal pedicled flap, and to some
operated cases in which there was no intraoperative CSF leak, which, in order not
to injure the nose more, we opted for closure only with synthetic material
-
Free mucosal graft: Fifty percent. They include patients of which any phase of the
study that it was not possible to obtain a pedicled flap because of previous surgeries
and to patients of the final phase in an attempt to be less aggressive, avoiding the
nasoseptal pedicled flap
-
Nasoseptal pedicled flap: Thirty seven. Although at one middle stage it was done routinely,
its use has finally been individualized, and it has been reduced only for those very
bulky adenomas with great suprasellar expansion and, therefore, high risk of CSF fistula.
[[Table 1]] and [[Figure 1]] show the personal history that could be related to the adenoma and the radiological
findings. We observe that there is no significant difference between the characteristics
of the cases of the free graft and pedicle groups, except for a slightly higher incidence
of previous surgery in the pedicled flap group, so we assume that the samples are
similar.
Table 1: Preoperative and surgical resection data
In relation to CSF leaks, intraoperative CSF output was observed in 29% of cases,
and a combination of the following elements was used for reconstruction: fat (35%),
dural substitute (43%) and sealant (94), combining them as we see in [[Table 2]]. Again, we observe that there were no significant differences between the free
graft group and the pedicled group in terms of the means used in the closure or in
the range of approaches.
Table 2: Intraoperative aspects related to the extension of the approach, and reconstruction
techniques used
Regarding the intraoperative CSF output, its rate was similar in both groups. Postoperatively,
no case of CSF fistula was diagnosed; only in one patient of the free graft group,
10 days after surgery, there was a doubtful CSF leak that would not be confirmed.
Given this suspicion, the patient was kept under hospital observation for 24 h, without
any treatment, and at no time CSF was observed, and hence, we suspect it was not a
true CSF leak.
As for other types of complications that could be related to the type of mucous reconstruction,
there were four cases of sinusitis throughout the series, two in the pedicled flap
group and two in the free mucosa group. There were five cases of epistaxis (one in
the group without flap and two in each of the groups with it), and as a common factor,
all of them had been under treatment with antiplatelet agents or anticoagulants, so
special attention should be paid to nasal hemostasis in these patients, regardless
of the type of reconstruction used.
Discussion
The main objective of the reconstruction of the cranial base after the removal of
an NFPA is to prevent CSF leak while maintaining good sinus health. The most reliable
reconstructive technique to achieve this objective is the nasoseptal pedicled flap,
but since it greatly alters the nasal anatomy leaving it devoid of mucosa in much
of the septum, different solutions have been sought, from trying to rebuild the donor
area to the use of mucosa-free grafts,[[15]] passing through other less physiological without mucosa[[2]],[[6]],[[7]],[[16]] such as fat, oxidized cellulose, collagen matrix or even not rebuild, and the use
of free flaps for the reconstruction of the cranial base.[[8]],[[11]],[[12]]
The key to minimizing the risk of CSF leak is to adapt our reconstruction to each
case. In general, if we believe that there will be an important outflow of CSF, a
nasoseptal pedicled flap is planned to be input, and in the surgical bed, we place
fat (sometimes with collagen matrix) that we cover with the obtained flap. If we do
not anticipate significant CSF output, a pedicled flap is not designed, and a middle
turbinate free mucosal graft will be placed. If there has been an outflow of CSF,
we will also place fat and/or collagen matrix below the free mucosa. Thus, before
placing the mucous flap, we will have reduced a part of the CSF flow, with which the
flap will heal more easily. Currently, in all cases, after one type or another of
flap, we apply a pulverized sealant. It should be taken into account that this series
includes patients operated for years, and today we design a rescue flap for doubtful
cases, and we are avoiding the right middle turbinectomy whenever possible.
Therefore, since the main objective of the reconstruction is to eliminate the risk
of postoperative CSF fistula, we need to plan preoperatively according to the risk
of intraoperative CSF leakage:
-
Minimum risk: Conventional approach without pedicle flap
-
Moderate risk: Rescue flap design (that could be turned into a pedicled flap)
-
High risk: Obtaining a nasoseptal pedicle flap.
To measure the severity of intraoperative CSF fistula, we used the classification
described by Esposito et al. [[Table 3]].[[17]] This classification will help us stratify the risk level of postoperative fistula,
and thus, we will adapt the reconstruction to that risk.
Table 3: Cerebrospinal fluid leak grading system
Therefore, our closure strategy will depend on the prediction of CSF output performed
preoperatively and on the degree of CSF output in the surgical field, for which the
following protocol is usually used[[18]] [[Figure 2]].
Figure 2: Algorithm for the management of the cerebrospinal fluid leak including the free mucosal
graft
Even though in 32% of cases of intraoperative CSF leak in the free mucosal graft group,
there were no postoperative leakage, which supports the data from recent studies of
Scagnelli[[11]] and Kuan,[[19]] where it is concluded that in cases with intraoperative high flow CSF leaks, as
happens after resection intradural lesions (meningiomas, craniopharyngiomas.,), the
cranial base must be reconstructed with pedicled flaps, while in cases of low flow
CSF leaks, such as those that occur after resection of pituitary adenomas, a free
mucosal graft is sufficient after reducing the dead space existing in the tumor cavity
with fat or collagen matrix.
We want to insist on some technical details for reconstruction with mucosa, especially
in free flaps, and since they are not vascularized, they are more sensitive to any
error in their implantation: the size must exceed the area of the defect to be closed
(several millimeters must be supported on the hard mother whenever it exists; if this
is not the case, they must do it on the mucous-free bone), and of course, do not make
the mistake of placing the flap upside down; that is, the face of the mucus-producing
cells must be the one that does not rest on the bone or dura mater. To avoid this
mistake, it is useful to place a sheet of oxidized cellulose (Surgicel) on one of
the sides of the flap to avoid doubts at the final moment of the placement of the
flap [[Figure 3]].
Figure 3: (a) Placing the free mucosal graft. It is easy to get a wide piece that covers a
lot of surface and has a thickness that makes it resistant (b) Sagittal magnetic resonance
image showing the closure of the cranial base with free mucosa, 6 months after resection
of a nonfunctioning pituitary adenoma
Regarding other measures to take into account, we believe that the use of silicone
sheets in the nostrils is important, with the aim of reducing the risk of synechiae,
and doing nasal washes with physiological saline. In those cases that intraoperative
CSF output has been observed, we recommend that patients maintain relative rest for
4 weeks, avoiding sports, efforts, and blowing their nose. Patients who use nocturnal
CPAP will interrupt it for 2–4 weeks.
Conclusions
It is very important to be flexible in terms of the reconstruction technique used
and individualize each case to create only the necessary nasal morbidity that allows
us to safely remove the adenoma, and perform a reconstruction of the selar floor with
the lowest risk of CSF fistula. Within this individualized management, the free mucosa
graft has an excellent result avoiding CSF fistulas and maintaining nasosinusal health,
so it must be included among the tools that can be used in the reconstruction of the
cranial base.
