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Year : 2020  |  Volume : 15  |  Issue : 4  |  Page : 946-951

Free mucosal graft for reconstruction after nonfunctional pituitary adenoma surgery

1 Department of Neurosurgery, University Hospital La Paz, Madrid, Spain
2 Department of Ear, Nose and Throat, University Hospital La Paz, Madrid, Spain

Date of Submission30-Jan-2020
Date of Decision20-Mar-2020
Date of Acceptance01-Jul-2020
Date of Web Publication19-Oct-2020

Correspondence Address:
Dr. Carlos Perez-Lopez
P° de la Castellana, 261, Department of Neurosurgery, University Hospital La Paz, 28046, Madrid
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajns.AJNS_37_20

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Background: In the search for an effective closure without nasosinusal morbidity, we have studied the efficacy of free mucosal graft as a reconstructive technique of the sellar floor after the resection of nonfunctioning pituitary adenomas (NFPA). Methods: In 100 endonasal endoscopic surgeries, we analyzed the personal history, radiological and intraoperative aspects that could have an impact on the risk of postoperative cerebrospinal fluid (CSF) leak. They were divided into three groups: no mucosa flap/graft, mucosal free graft, and nasoseptal pedicled flap. Results: The characteristics of the patients and adenomas were the same in all three groups. Intraoperative CSF leak was observed in 1/13 cases of the group without graft/flap (7%), in 16/50 of the free mucosal graft (32%) and 12/37 (32%) of pedicle flap. The proportion of cases in which other means of reconstruction were used in addition (fat, collagen matrix, and sealant) was similar in the different groups. No CSF leaks were observed, except for a doubtful one in the free mucosal graft group, which resolved spontaneously within 24 h, without receiving any type of treatment. Conclusions: The middle turbinate free mucosal graft can be of great value in endonasal surgery: It achieves a hermetic closure in cases of low-flow CSF leaks, it can be useful as a rescue for cases where nasoseptal mucosa is not available to perform a pedicled nasoseptal flap, minimizes the nasosinusal complications of the pedicled flap by leaving a smaller surface area of the nasal cavity devoid of the mucosa, and achieves greater nasosinusal functionality because proper reepithelialization occurs in the area.

Keywords: Adenoma, cerebrospinal fluid leak, free mucosal graft, nonfunctioning

How to cite this article:
Perez-Lopez C, Palpan AJ, Zamarrón ┴, Alfonso C, De Arriba ┴, Giner J, Isla A. Free mucosal graft for reconstruction after nonfunctional pituitary adenoma surgery. Asian J Neurosurg 2020;15:946-51

How to cite this URL:
Perez-Lopez C, Palpan AJ, Zamarrón ┴, Alfonso C, De Arriba ┴, Giner J, Isla A. Free mucosal graft for reconstruction after nonfunctional pituitary adenoma surgery. Asian J Neurosurg [serial online] 2020 [cited 2021 Jan 18];15:946-51. Available from:

  Introduction Top

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 Top

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

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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 Top

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

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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

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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 Top

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

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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

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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

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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 Top

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.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Fernandez-Miranda JC, Prevedello DM, Gardner P, Carrau R, Snyderman CH, Kassam AB. Endonasal endoscopic pituitary surgery: is it a matter of fashion? Acta Neurochir (Wien) . 2010;152:1281-2.  Back to cited text no. 1
Dehdashti AR, Ganna A, Karabatsou K, Gentili F. Pure endoscopic endonasal approach for pituitary adenomas: Early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 2008;62:1006-15.  Back to cited text no. 2
Sanders-Taylor C, Anaizi A, Kosty J, Zimmer LA, Theodosopoulos PV. Sellar Reconstruction and rates of delayed cerebrospinal fluid leak after endoscopic pituitary surgery. J Neurol Surg Part B Skull Base 2015;76:281-5.  Back to cited text no. 3
Kassam AB, Prevedello DM, Carrau RL, Snyderman CH, Thomas A, Gardner P, et al. Endoscopic endonasal skull base surgery: Analysis of complications in the authors' initial 800 patients. J Neurosurg 2011;114:1544-68.  Back to cited text no. 4
Hadad G, Bassagasteguy L, Carrau RL, Mataza JC, Kassam A, Snyderman CH, et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: Vascular pedicle nasoseptal flap. Laryngoscope 2006;116:1882-6.  Back to cited text no. 5
Jang JH, Kim KH, Lee YM, Kim JS, Kim YZ. Surgical results of pure endoscopic endonasal transsphenoidal surgery for 331 pituitary adenomas: A 15-year experience from a single institution. World Neurosurg 2016;96:545-55.  Back to cited text no. 6
Paluzzi A, Fernandez-Miranda JC, Tonya Stefko S, Challinor S, Snyderman CH, Gardner PA. Endoscopic endonasal approach for pituitary adenomas: A series of 555 patients. Pituitary 2014;17:307-19.  Back to cited text no. 7
Kimple AJ, Leight WD, Wheless SA, Zanation AM. Reducing nasal morbidity after skull base reconstruction with the nasoseptal flap: Free middle turbinate mucosal grafts. Laryngoscope 2012;122:1920-4.  Back to cited text no. 8
Soudry E, Psaltis AJ, Lee KH, Vaezafshar R, Nayak JV, Hwang PH. Complications associated with the pedicled nasoseptal flap for skull base reconstruction. Laryngoscope 2015;125:80-5.  Back to cited text no. 9
Zamorano J, Pérez López C, Pérez Zamarrón A, García Polo J, Alfonso C. Free mucosae flap in endoscopic endonasal skull base surgery: Less nasosinusal morbidity. In XIII Congreso de la Sociedad Española de Neurocirugía 2003.  Back to cited text no. 10
Scagnelli RJ, Patel V, Peris-Celda M, Kenning TJ, Pinheiro-Neto CD. Implementation of free mucosal graft technique for sellar reconstruction after pituitary surgery: Outcomes of 158 consecutive patients. World Neurosurg 2019;122:e506-e511.  Back to cited text no. 11
Peris-Celda M, Chaskes M, Lee DD, Kenning TJ, Pinheiro-Neto CD. Optimizing sellar reconstruction after pituitary surgery with free mucosal graft: Results from the first 50 consecutive patients. World Neurosurg 2017;101:180-5.  Back to cited text no. 12
Egger J, Kapur T, Nimsky C, Kikinis R. Pituitary adenoma volumetry with 3D Slicer. PLoS One 2012;7:e51788.  Back to cited text no. 13
Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: A magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993;33:610-7.  Back to cited text no. 14
Yoo F, Kuan EC, Bergsneider M, Wang MB. Free mucosal graft reconstruction of the septum after Nasoseptal flap harvest: A novel technique using a posterior septal free mucosal graft. J Neurol Surg Part B Skull Base 2017;78:201-06.  Back to cited text no. 15
Gondim JA, Schops M, de Almeida JP, de Albuquerque LA, Gomes E, Ferraz T, et al. Endoscopic endonasal transsphenoidal surgery: Surgical results of 228 pituitary adenomas treated in a pituitary center. Pituitary 2010;13:68-77.  Back to cited text no. 16
Esposito F, Dusick JR, Fatemi N, Kelly DF. Graded repair of cranial base defects and cerebrospinal fluid leaks in transsphenoidal surgery. Oper Neurosurg (Hagerstown) 2007;60:295-303.  Back to cited text no. 17
Conger A, Zhao F, Wang X, Eisenberg A, Griffiths C, Esposito F, et al. Evolution of the graded repair of CSF leaks and skull base defects in endonasal endoscopic tumor surgery: trends in repair failure and meningitis rates in 509 patients. J Neurosurg. 2018;130(3):861-75.  Back to cited text no. 18
Kuan EC, Yoo F, Patel PB, Su BM, Bergsneider M, Wang MB. An algorithm for sellar reconstruction following the endoscopic endonasal approach: A review of 300 consecutive cases. J Neurol Surg B Skull Base 2018;79:177-83.  Back to cited text no. 19


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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