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Home > Books > Skull Base Surgery - Pearls and Nuances
Open access peer-reviewed chapter
Written By
Nazik Abdullah, Haytham Osman, Honida Ibrahim, Khalid Elzein and Ali Awad
Submitted: 01 September 2023 Reviewed: 02 September 2023 Published: 07 March 2024
DOI: 10.5772/intechopen.1003030
From the Edited Volume
Skull Base Surgery - Pearls and Nuances
Amit Agrawal
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Abstract
Pituitary neoplasm is the commonest sellar pathology, where pituitary adenoma heads the list, it accounts for 25% of all intracranial neoplasm. Although it is a benign lesion in most cases is located in a complex region; adjacent to important structures: optic chiasm, internal carotid arteries, suprasellar cistern, and cavernous sinuses, it presents with a variety of clinical scenarios. The Sella is situated at the center of the skull base, this made surgical access via craniotomy very challenging and is associated with considerable morbidity. Transnasal endoscopic pituitary surgery (TEPS) evolved rapidly, almost replacing the craniotomy approach, because it is minimally invasive and gives direct sellar access with excellent visualization. On the other hand, the learning curve of TEPS requires meticulous training to acquire surgical skills. Indications of TEPS, technique, complications, their prevention, and management are described. The multidisciplinary approach in managing pituitary adenoma is addressed, where a team of an endocrinologist, neurosurgeon, otolaryngologist, ophthalmologist, anesthesiologist, and neuroradiologist decide on a management plan for patients. Other disciplines share management of certain cases that is Oncologist, ICU specialists, and obstetrician. Long term follow-up is required by endocrinologists whereas revision surgery is considered in some patients.
Keywords
- pituitary adenoma
- transnasal
- endoscopic
- surgery
- skull base
- reconstruction
- nasoseptal flap
- CSF
Author Information
Nazik Abdullah*
- Khartoum ENT Hospital, Khartoum, Sudan
- Department of Otolaryngology, University of Khartoum, Khartoum, Sudan
Haytham Osman*
- Ribat University Hospital, Neurosurgery Center, Khartoum, Sudan
- Department of Surgery, The National Ribat University, Khartoum, Sudan
Honida Ibrahim*
- Ribat University Hospital, Neurosurgery Center, Khartoum, Sudan
Khalid Elzein
- Department of Surgery, The National Ribat University, Khartoum, Sudan
- Otolaryngology Department, Ribat University Hospital, Khartoum, Sudan
Ali Awad
- Ribat University Hospital, Neurosurgery Center, Khartoum, Sudan
*Address all correspondence to: nazikfad1223@yahoo.co.uk, haytham2ta@hotmail.com and honida2075@gmail.com
1. Introduction
The pituitary gland is situated at the center of the skull base, in a saddle-like bone, the Sella, a complex anatomical region with critical neurovascular structures adjacent. This gland has a vital physiological function by acting as the chief controller of all the endocrine glands in the body. The complex anatomy, physiology, and clinical presentation of pathology made the journey of patients with pituitary tumors very challenging. Treatment goals of pituitary tumors are to relieve pressure on surrounding important structures, normalize hormone levels, and improve neurological deficits. Options of treatment include surgery, medical therapy, radiation therapy, or a combination in an individualized patient’s approach. Treatment choice depends on hormonal status, tumor size, type, and extension.
According to authors’ experience, the decision of management plan, which includes the diagnosis, treatment, perioperative care, and follow is being taken by a dedicated formal multidisciplinary team, the team includes members from each of the following departments, endocrinology, neurosurgery, ophthalmology, otolaryngology, radiology, anesthesia/ICU and oncology. This team was created in the year 2017, and the importance of this team approach is thoroughly addressed later, in summary, it optimizes treatment options, improves the outcome of surgery, and reduces the complications rate.
Transnasal endoscopic pituitary surgery (TEPS) is an evolutionary approach to the management of pituitary tumors. This approach is minimally invasive, it utilizes the endoscope transnasally, without the requirement of external scalp incision and craniotomy. The endoscope allows for better visualization of the surgical field and consequently precise, safe, and effective surgical resection.
This procedure requires extensive knowledge of normal anatomy and anatomical variations, meticulous training, and surgical auditing to catch the learning curve. To master the skills of this surgery, both baseline training and continuous lifelong learning are required, these include hands-on cadaveric dissection and training on simulation models. The authors started endoscopic pituitary surgery in a center of excellence after creating a multidisciplinary team in 2017, bearing in mind that it is in a low-resource country and a limited facility center, and despite the unavailability of neuro-navigation as routine, the outcome of surgery is satisfactory and improving, the complications are becoming less and more complicated cases are being operated. The surgeons, both neurosurgeons and otolaryngologists, were already well trained in endoscopic surgery with a wealthy experience before commencing pituitary endoscopic surgery.
The authors have experience of very advanced pathology with massive extension and late presentation of patients, the majority present with impaired vision, being referred from the ophthalmology department rather than the general practitioner, due to limited access to primary health services and delayed referrals. This puts a further burden on the team, particularly with the limited facilities. The authors’ experience is unique, dealing with advanced cases with limited facilities, yet a reasonable outcome, implementing the “Do more with less” strategy.
2. Anatomy of the sella and suprasellar region
2.1 Anatomy of the sellar region
The anatomy of the gland has important clinical and surgical implications. The pituitary gland is situated in the pituitary fossa, also named the hypophyseal fossa or the sella turcica, a bony saddle as the name indicates in Latin. This bony saddle is located at the center of the skull base, it is fibro-osseous. The roof of the sphenoid sinus forms the floor of the pituitary fossa, this is demonstrated in the CT scan in Figure 1 The sella turcica is bounded by bone, anteriorly, inferiorly, and posteriorly. The pituitary fossa is roofed by the diaphragma sellae, a dural fold with a central aperture; covering the fossa incompletely,
Laterally, the cavernous sinus is separated from the pituitary gland by a dural fold that forms the medial wall of the cavernous sinus. Antero-superiorly lies the optic chiasm, separated from the pituitary gland by the diaphragma sellae [1, 2, 3].
2.2 Variations of pituitary gland and sellar region
Variations of the gland should be taken into consideration when planning surgery, they may lengthen duration of resection, and some are dangerous leading to life-threatening complications [4].
The weight of the gland is variable according to gender. During pregnancy, the gland’s weight increases and even doubles. The shape of the gland can be altered by pressure of the internal carotid arteries, leading to flattening of the pituitary gland. There is variation in the height of the gland, it ranges from 3 to 11mm. When the gland does not fill the hypophyseal fossa, the suprasellar arachnoid cistern descends and encroaches on the fossa, in this case, it becomes a sellar component. The distance between the optic chiasm and the tuberculum sellae is very variable, it ranges between 1.5 to 8mm. The sphenoid sinus is located on sellar floor, its extent of pneumatization is crucial in the accessibility of the sella during surgery when the transnasal approach is used [4].
A sellar type, where the sphenoid pneumatization extends well around the sellar floor is favorable for a transnasal approach as demonstrated in Figure 2, contrary to the conchal type, where access to sellar floor is difficult due to thick bone, in this case, image guide radiology is helpful to prevent complications, e.g., unintentional injury of important neighboring structures.
2.3 Parasellar and suprasellar anatomy
The cavernous sinus and the suprasellar cistern encompass the parasellar region. The lateral walls of the pituitary fossa are made up of dura mater, and it contains the cavernous sinus. The cavernous sinus consists of the internal carotid artery, sympathetic fibers, and cranial nerves III, IV, V, and VI. The suprasellar cistern encompasses the optic chiasm, part of the third ventricle, the hypothalamus, and the tuber cinereum [2, 5].
2.4 Blood supply of the pituitary gland
The pituitary gland is enriched with blood supply, it is a well-vascularized organ. The hypothalamo-hypophyseal portal system connects the blood supply of the gland with the hypothalamus. This connection is very important in regulating the secretory function of the gland, it will be discussed later in the physiology section.
The anterior lobe of the gland receives its blood supply from the superior hypophyseal artery, which originates either from the internal carotid artery or the posterior communicating artery. The posterior lobe of the gland receives its blood supply from the inferior hypophyseal artery which originates from the meningo-hypophyseal artery which is a branch of the internal carotid artery. The intermediate lobe receives blood from the capillaries of the anterior and posterior lobes. The pituitary stalk and parts of the optic nerve and chiasm are supplied by branches from the superior hypophyseal artery. A primary plexus is formed from the internal carotid artery and the posterior communicating artery, it supplies the median eminence, and the hypothalamic cells end at the median eminence, hence the primary plexus receives regulatory factors. Capillaries from all lobes form venules, these venules form the secondary plexus, and the latter drain into the cavernous sinus
2.5 Histology of the pituitary gland
The pituitary gland is composed histologically of two parts, the adenohypophysis, and the neurohypophysis.
2.5.1 Adenohypophysis
It is a secretory part, responsible for hormone production and secretion. It is composed of well-defined acini, there are six cell lines, five of which are hormone-producing cell lines, namely: Somatotrophs, lactotrophs, corticotrophs, thyrotrophs, and gonadotrophs. The folliculostellate cells form the sixth cell line, which is a nonhormone-producing cell line.
The following structures make up the anterior pituitary gland:
Pars distalis, it forms most of the bulk of the anterior pituitary gland, it is composed of cells that produce hormones, arranged in the form of follicles of different sizes. Based on the staining characteristics, the hormone-producing cells are classified as:
Acidophils: The cytoplasm stains red, they are composed of polypeptide hormones. Soamtptrophs and lactotrophs are acidophils.
Basophils: The cytoplasm stains blue to purple, they are composed of glycoproteins, thyrotrophs, gonadotrophs, and corticotrophs are basophils.
Chromophobes: As the name states, they do not stain. Stem cells that are yet to differentiate into hormone-producing cells form this cell line.
Pars Tuberalis: The tubular stalk has anterior and posterior parts. It encircles the infundibular stem. The infundubular stem is composed of unmyelinated axons, that originate from the hypothalamic nuclei. Two hormones accumulate in these axons; oxytocin and vasopressin, in the form of ovoid eosinophilic swellings along the stem of the infundibulum. They make the herring bodies.
Pars intermedia: It is located between the pars distalis and the posterior pituitary gland. Follicles containing a colloid matrix form the pars intermedia, it includes the reminder of Rathke’s pouch cleft. Melanocyte-stimulating hormones and endorphins are produced by these cells.
The initial primary signal hormones are synthesized in the hypothalamus to stimulate the pituitary gland. Production of these primary signal hormones is in the cell body of the neurons, the axons project to end at the gland in the fenestrated portal capillaries. They are then carried
2.5.2 Neurohypophysis
This is a specialized neuroendocrine structure.
It is composed of both, pars nervosa and the infundibular stalk. The axons that originate in the hypothalamus, form the neurohypophysis. These axons are encircled by glial cells called the pituicytes. The pituicytes have elongated processes that run along with the axons. The axons form the hypothalamo-hypophyseal tract, which terminates near the posterior lobe sinusoids [1].
2.6 Embryology of the pituitary gland
Two different origins form the pituitary gland. The adenohypophysis is derived from the oral ectoderm. The neurohypophysis is derived from neural ectoderm. The posterior lobe is derived as an extension of the central nervous system (third ventricle neural primordia) [3].
3. Physiology of the pituitary gland
The following are the hormones produced and secreted from the anterior pituitary: Adrenocorticotropic Hormone (ACTH), Prolactin (PRL), Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), Growth Hormone or Somatotropin (GH) and Thyroid Stimulating Hormone (TSH) [6, 8, 9, 10]. Two hormones are released from the posterior pituitary: Oxytocin and Arginine Vasopressin (AVP) or Antidiuretic Hormone (ADH) [9, 11, 12, 13].
4. Pathology
Endocrine and neurological disorders are encountered in the sellar region, due to neoplasms arising from the adenohypophysis, such as pituitary adenoma, which heads the list ardently, it is associated with excessive hormonal production, examples are acromegaly and Cushing’s disease, other pathologies include cysts or tumors derived from remnants of Rathke’s pouch (Rathke’s cleft cyst, craniopharyngioma), tumors derived from the neurohypophysis and pituitary stalk (pituicytoma and granular cell tumor) and tumors of the parasellar bone (chordoma). Further, conditions such as lymphocytic or granulomatous hypophysitis, present clinically like tumors [3].
Pituitary adenomas are common intracranial tumors, they are benign clonal neoplasms, originating from the endocrine epithelial cells of the adenohypophysis. Adenoma of the pituitary gland has a wide spectrum of presentation, in 22%, it is clinically silent and discovered accidentally on MRI scans of the brain, around 14% are autopsy finding, and It accounts for 25% of clinically apparent intracranial tumors [3, 4].
Pituitary adenoma in common with other adenomas of endocrine origin, share the following characteristics: round nuclei with finely dispersed chromatin, distinct multiple nucleoli, and granular cytoplasm. They express both markers of neurosecretory granules and epithelial differentiation. Wide morphological features of pituitary adenoma are described based on hormonal, or genetic subtype, or due to treatment effect. Pituitary adenoma is a benign neoplasm, but it can be locally invasive and destructive. Excess hormone secretion gives rise to metabolic disorders that render it malignant on a clinical basis [3].
4.1 WHO classification
According to the following factors, pituitary adenomas are classified: size, clinically silent or functional, hormone or cytokeratin expression profile, histologic features, or somatic mutations. Markers of cytodifferentiation are the principal classifiers in the 2004 edition of the WHO classification of endocrine tumors. Adenoma is further categorized into typical pituitary adenoma, pituitary carcinoma, and atypical pituitary adenoma [14]. The criteria of atypia are subjective, and the clinical significance is ill-defined, this warrants the need for longitudinal studies to label atypia [15]. The current 2004 classification is described in Table 1 [16, 17, 18].
| Adenoma type | Transcription Factors | Hormones | Cytokeratin |
|---|---|---|---|
| Densely granulated somatotroph adenoma | Pit-1 | GH, a-SU | diffuse |
| Sparsely granulated somatotroph adenoma | Pit-1 | GH | dot-like |
| Mammosomatotroph adenoma | Pit-1, ER | GH, PRL, a-SU | diffuse |
| Mixed somatotroph and lactotroph andenoma | Pit-1, ER | GH, PRL, a-SU | diffuse |
| Sparsely granulated lactotroph adenoma | Pit-1, ER | PRL (Golgi) | diffuse |
| Densely granulated lactotroph adenoma | Pit-1, ER | PRL (diffuse) | diffuse |
| Acidophil stem-cell adenoma | Pit-1, ER | PRL (diffuse), GH | rare dot-like |
| Thyrotroph adenoma | Pit-1, GATA-2 | b-TSH, a-SU | diffuse |
| Densely granulated corticotroph adenoma | Tpit | ACTH | diffuse |
| Sparsely granulated corticotroph adenoma | Tpit | ACTH | diffuse |
| Crooke’s cell adenoma | Tpit | ACTH | ring-like |
| Gonadotroph adenoma | SF-1, GATA-2, ER | b-FSH, b-LH, a-SU | diffuse |
| Plurihormonal adenomas | |||
| Silent type III adenoma | Pit-1 (?), ER | Multiple | diffuse |
| Unusual plurihormonal adenoma (NOS) | multiple | Multiple | n/a |
| Null cell adenoma | None | None | diffuse |
Table 1.
Classification according to side is described as follows: Microadenomas (<10 mm) which are often within the Sella turcica, macroadenomas (≥10 mm) which may be contained in the Sella turcica but also infiltrate into the superior, inferior, and or lateral extrasellar space, and giant adenomas (≥40 mm).
5. Symptoms and signs
The presentation of pituitary adenoma depends on tumor size and functional status [19, 20].
Pituitary microadenoma (less than 1cm) is usually an incidental finding on MRI Brain and patients are asymptomatic unless the tumor is hormonally active, while pituitary macroadenoma (more than 1cm) presents with symptoms and signs of space-occupying lesion in addition to hormonal deficiency or hormonal excess. Pituitary apoplexy is a complicated adenoma, where sudden hemorrhage ensues into the adenoma, it presents with severe headache and acute vision changes besides mass effect.
5.1 Symptoms from mass effect (nonfunctioning adenoma)
5.1.1 Visual impairment
Vision changes occur in 40–60% of patients. It presents as bitemporal defect in most cases, followed by hom*onymous defect and diplopia. Suprasellar extension of large pituitary tumors compress the optic chiasm leading to the previously mentioned visual field defects and impaired acuity, while Involvement of cranial nerves by invasive tumors explains diplopia and blindness [21, 22].
5.1.2 Headache
Headache is commonly reported in pituitary adenoma; however, it is a non-specific symptom [22]. It is of sudden onset and severe in apoplexy as mentioned earlier.
5.1.3 Hormonal deficiency
Patients with pituitary adenoma may present with hormonal deficiencies, where one or more hormones of the anterior pituitary are deficient. In gonadotrophin deficiency, females present with amenorrhea, and males present with erectile dysfunction. Growth hormone (GH) when deficient in adults, presents with fatigue and weight loss. Thyroid Stimulating Hormone deficiency (TSH) leads to weight gain, fatigue, constipation, and cold intolerance. Symptoms of Adrenal Cortical Stimulating Hormone (ACTH) deficiency are those of hypoadrenalism; fatigue, weight loss, arthralgia, dizziness, nausea, low blood pressure, and abdominal pain.
5.1.4 Case scenario no (1)
A 44-year-old male, with no significant past medical history, presented to the ER with a history of sudden loss of vision for 1day preceded by severe headache. No history of loss of consciousness. Examination revealed a fully oriented person with intact higher functions, he was totally blind (fundus examination revealed papilledema grade 4). Investigations: Hormonal profile showed features of panhypopituitarism. Brain MRI showed sellar lesion with suprasellar extension. Clinically and radiologically, the diagnosis of apoplexy was made. Intraoperatively soft tumor tissues were retrieved with hematoma and infarcted debris as in Figures 3–6. Marked improvement of vision was acheived, immediately postoperatively.
5.2 Symptoms of functioning adenomas
Patients with secreting adenomas present according to the hormone being excessively produced, the following clinical scenarios are observed:
5.2.1 Prolactin-secreting adenomas
High levels of prolactin suppress the gonadotrophin levels leading to infertility, osteoporosis, and decreased libido in males and females. Males present with gynecomastia and erectile dysfunction and females present with amenorrhea and galactorrhea.
5.2.2 GH-secreting adenoma (acromegaly)
Patients complain of headaches, vision changes, and an increase in ring size and shoe size, others present with carpal tunnel syndrome and excessive sweating. On examination, they have coarse facial features, frontal bossing, enlarged nose, protruded mandible, and an enlarged tongue. Hypertension, cardiomyopathy, multiple colonic polyps, and obstructive sleep apnea are comorbidities.
5.2.3 ACTH-secreting adenoma (Cushing’s disease)
Weight gain is the chief complaint, others include muscle weakness, mood disorders, easy bruising, and multiple fractures. Clinically, patients have moon face, supraclavicular fat, ecchymoses, and striae on armpits and abdomen.
5.2.4 TSH secreting adenoma
Patients present with palpitations, weight loss, heat intolerance, and arrythmias. A goiter and tremors are usually obvious features.
5.2.5 Case scenario No (2)
A 39-year-old lady presented with features of acromegaly and secondary infertility, no other symptoms, hormone profile revealed an elevated growth hormone level. MRI showed pituitary macroadenoma as in Figure 7, transnasal endoscopic pituitary surgery was performed. This lady showed obvious improvement in acromegaly features, and she delivered a baby girl 1 year after surgery.
6. Radiological assessment of pituitary lesions
The image of choice of the pituitary gland is MR. Thin sections (1–2) mm are required to have detailed study of the sellar region, thin cuts are performed in both the coronal and sagittal planes. The mainstay of pituitary imaging is T1 weighted sequences, pre and post contrast [23]. Post contrast MR sequences in dynamic fashion (during the first minute) after contrast injection is of great benefit, as it maximizes the visibility of adenomas within the pituitary gland, which typically shows less enhancement than the normal pituitary tissue, this differential enhancement is best addressed within the first arterial phase of contrast injection. In the majority of pituitary adenomas, they are well demonstrated on a standard acquisition (non-dynamic) scan after contrast injection [24]. The high field strength 3 Tesla MR scanners, which are replacing the 1.5 Tesla machines, provide high-resolution pituitary images.
Excellent soft tissue characterization is well provided by MRI, in the contrary, CT does not provide this, but can be useful for investigation when MR is contraindicated or unavailable, or if identification of calcification around the sella is significantly required [25]. CT of the nose and sinuses is essential if surgery is indicated, where anatomical variations and sphenoid pneumatization are identified preoperatively. Figure 8 demonstrates bilateral concha bullosa.
7. Treatment and management
Management of pituitary tumors requires a team approach with participation from the following departments: Internal medicine, endocrinology, ophthalmology, radiology, neurosurgery, ENT, and anesthesia/ICU. A specialized neuroradiologist is an important team member as MRI needs to be done with the pituitary protocol.
7.1 Treatment of non-functioning adenomas
Surgery is indicated in the presence of one or more of the following conditions [26]:
Vision change, for example, visual field defect, ophthalmoplegia, and sudden vision loss
Compression of the optic nerve or optic chiasm on imaging
Pituitary apoplexy with visual disturbances
Hypopituitarism
Significant growth of pituitary tumor over time
Pituitary adenomas, when less than 1cm is labeled as microadenomas, although there is no clinical significance of this threshold, a cut-off of 20 or 30mm is demonstrated to be more relevant, therefore more studies are needed to examine the significance of classification according to size, and probably to reset a cut-off size. One study concluded that there was no difference in the rate of surgery or survival for pituitary adenomas in the range of 30–50mm, questioning the 4-mm cut-off threshold for labeling giant pituitary adenoma [27].
Surgery is aimed at improvement in visual symptoms and improvement of hormonal dysfunction. Most patients improve. Radiotherapy is a choice for patients with persistent or residual tumors.
Annual follow-up is required for nonfunctional adenomas that do not require surgery, endocrinological and radiological follow-ups (by MR,) are performed to assess the development of hypopituitarism and tumor growth.
7.2 Treatment of individual functioning tumors
7.2.1 Prolactin secreting adenomas
The first line of treatment for prolactin-secreting tumors is Dopamine Agonists (DA) e.g. Cabergoline and bromocriptine. Cabergoline controls prolactin secretion in more than 90% of tumors. Tumors regress in size accordingly, and when there is no longer tumor in the MRI, cabergoline is discontinued after 2 years. Annual monitoring of prolactin levels is required to detect recurrence after stopping cabergoline. Prolactin-secreting tumors that are resistant to cabergoline are treated by surgical resection. Other indications of surgery are the development of adverse effects of dopamine agonists that require cessation, patients who desire pregnancy, and tumors more than 1cm.
When medications and frequent surgery fail to control tumor size, prolactinoma is then labeled as aggressive, in this case, radiotherapy is indicated.
7.2.2 GH secreting adenomas
Surgery is the first line for GH-secreting adenoma. Surgery is effective in 80–90% of microadenoma and in 40–60% of macroadenoma. Medical treatment (somatostatin analog) is offered for patients with persistently elevated levels of growth hormone after surgery and for inoperable invasive tumors.
Radiation therapy, although lately effective, is deferred for patients with elevated GH after surgery.
7.2.3 ACTH secreting adenoma
Cortisol levels are reduced rapidly by surgical resection of pituitary tumors. This is the first line of treatment for Cushing’s disease, surgery is effective in 70–90% of patients. Although bilateral adrenalectomy is effective in leading to immediate relief of hypercortisolemia, it results in adrenal insufficiency, which requires lifelong supplements.
Medications that reduce ACTH secretion are cabergoline and SSA (pasireotide, pasireotide LAR). Others include ketoconazole, metyrapone, mitotane and etomidate. Mifepristone is a glucocorticoid blocker used in selected cases.
Radiotherapy is an adjuvant after surgery and medical treatment.
7.2.4 TSH secreting adenoma
The first line of treatment is pituitary surgery with a 50–90% cure rate. Hyperthyroidism is controlled before surgery to avoid a thyroid storm. Patients who are not cured by surgery can be treated with SSA to decrease both TSH levels and tumor size, failure of SSA implies its combination with radiation therapy [26].
8. Preoperative preparation and interprofessional team approach
Patients with pituitary tumors require a combined approach and coordination between the endocrinologist, the neurosurgeon, the ophthalmologist, the ENT surgeon, and the anesthesiologist.
Surgical outcome depends on preoperative status and assessment, intraoperative events, and postoperative complications therefore, patients’ counseling is very important; the expectations and anticipated complications should be discussed and explained to the patient clearly, in this regard the input from each department is crucial.
Preoperative routine tests include complete blood count, electrolytes, liver function test, urine analysis, and coagulation profile. Endocrine assessment by assay of pituitary hormones and hormones of related glands are included. N.B. women with amenorrhea should always have a pregnancy test. Any preoperative manifestations or diseases secondary to pituitary dysfunction must be controlled.
Abnormal thyroid function test and adrenal gland dysfunction must be detected preoperatively, and normalized. Hydrocortisone is administered only to patients with low levels of corticoids as a replacement. Comorbidities associated with acromegaly and Cushing’s disease should be evaluated thoroughly.
MRI head with pituitary protocol, CT scan of the nose and sinuses with nasal endoscopy by ENT surgeon are prerequisite for surgery. A swab from the nasopharynx is taken for bacteriology study to confirm pathogen-free nasal mucosa. Optimal intraoperative management depends on the indication for surgery and patient’s disease. The advantage of rapid emergence from anesthesia is that it allows for early neurologic assessment, where common and serious surgical complications are identified [28].
9. Anesthetic management
Maintenance of hemodynamic stability, adequate cerebral perfusion and oxygenation, appropriate position of the patient, excellent surgical exposure, and quick recovery from anesthesia to assess neurological signs are the main goals of anesthetic management [14, 29].
A pharyngeal pack is placed after endotracheal intubation to prevent aspiration and filling of the stomach with debris, this will reduce post-operative nausea and vomiting. Local anesthetic application and vasopressin to the mucosal surfaces result in systemic hypertension and cardiac arrhythmia. These are transient effects and are treated with short-acting medications. Myocardial ischemia has been reported when vasoconstrictors are used excessively.
Fixation of endotracheal tube is very important, to prevent dislodgement as endotracheal tube is inaccessible during the operation.
Compression stockings are of paramount importance to prevent deep vein thrombosis with consequent pulmonary embolism.
Regarding the choice of anesthetic agents, it is like intracranial surgeries, and it depends on the patient’s comorbidities.
10. Surgical treatment of pituitary tumors
10.1 Surgical approaches for pituitary tumors and patient selection
Surgery of the pituitary gland evolved from transcranial approach to transnasal transsphenoid approaches, either using the microscope or the endoscope [30, 31].
Fibrous tumors, failure of transsphenoidal resection, and dumbbell tumors that pass
The transcranial approach is claimed to have a greater visual improvement for long-term pituitary adenomas, nevertheless, it has a greater risk of postoperative pituitary dysfunction [32, 33, 34].
10.2 The learning curve
Transnasal endoscopic pituitary surgery (TEPS) has a learning curve like every other surgical technique. Results are not satisfactory at the beginning of the learning curve, however after achieving this curve the complications are reduced significantly. To master endoscopic pituitary surgery a range of 17–50 surgeries are required [35, 36].
Operative time decreases significantly in simple tumors; complex operations would have a longer learning curve. Similarly the gross tumor resection (GTR) rate, shows a gradual and continuous learning process [37].
Attending workshops, hands-on cadaveric dissection, practice on models, and observation of live surgeries are essential for skills acquisition. A training model using a skull and eggs is useful to improve surgical techniques in TEPS [38].
10.3 Patient selection
For a beginner surgeon, favorable cases are started with. The criteria for selecting patients are nonfunctioning adenoma, tumors confined to the sella without supra or parasellar extension, and a well-pneumatized sphenoid sinus. Unfavorable factors are extensive tumors with parasellar or suprasellar extension, dumbbell tumors, recurrent tumors, conchal/presellar sphenoid sinus, and associated acromegaly or Cushing’s disease.
10.4 Preoperative radiological study and planning
MRI with pituitary protocol and CT of the nose, sinuses, and skull base are basic radiological investigations.
Checklist for radiological assessment [39]:
Size of nasal airway; it is jeopardized by deviated nasal septum and concha bullosa.
Anatomy of paranasal sinuses; extent of pneumatization, intra/inter-sphenoid septa, Onodi cell or concha bullosa.
Presence of sinus infection, as this delays pituitary surgery until it is cleared medically or surgically.
Anatomy of the sella; bony defects, anatomical variations, and abnormal carotid anatomy.
If the tumor is hypointense in T1, it is more likely to be firm in consistency.
Size of the tumor, a giant tumor may require an additional craniotomy approach or the presence of hydrocephalus as in Figure 9.
Extension of the tumor-like suprasellar and para sellar involvement, involvement of nearby structures, and encasem*nt of carotid artery or invasion of cavernous sinus
Identification of the normal pituitary gland.
Radiological features of apoplexy
Optic chiasm identification
Pituitary stalk deviation
10.5 Surgical stages
Surgery is divided into 4 stages: Nasal, sphenoid, sellar, and reconstruction stages as demonstrated briefly in the surgical video.
10.6 Operative room setup, equipment, and endoscopes
The operation room should be spacious to accommodate the necessary equipment, instruments, and personnel. The operating room plan is shown in Figure 10.
In nasal sphenoid and reconstruction stages, the main surgeon is on right side of the patient. The second surgeon; one on the right side of the surgeon and the third surgeon across the patient. In sellar stage, the main surgeon exchanges position with the second surgeon as shown in Figure 11, the latter holds the endoscope to allow for three and/or four hands technique.
It is essential to supply the operative room with an appropriate surgical instrumentation, to optimize the different stages of the operation. Equipment should include an up-to-date endoscopic unit; A high definition resolution screen adds to accuracy in visualization and hence precision in surgery, an image-guided monitor, set for endoscopic nasal surgery, Cappabianca set for skull base and pituitary surgery, and powered instruments; micro-debrider and a high-speed drill. Bipolar suction diathermy is an important surgical tool as it provides a bloodless surgical field with good visualization.
Different degrees of endoscopes add to surgical field revelation, the sheath makes the surgeon’s grip more stable, and the irrigation system lessens the in-and-out movement of the endoscope for cleaning. Cappabianca set is a set of instruments designed for endoscopic skull base and pituitary surgery, the instruments are longer than nasal surgery pieces, and unlike the bayonet for microscopic surgery are straight [40, 41]. Summary of instruments required for each stage is presented in Table 2. Image guidance is very important intraoperatively, when there are nasal anatomical variations like Onodi cell, deviated nasal septum, conchal or presellar sphenoid, kissing carotids and in revision surgery. In most of the centers it is a routine adjunct during surgery.
| Surgical stage | Endoscope | Instrument |
|---|---|---|
| Nasal stage & Sphenoid stage | Endoscope 0°, Length 18cm, Diameter 4mm, 5mm External sheath and irrigation system and anti-fog | Nasal endoscopy set Micro-debrider High speed Drill Bipolar diathermy ± Navigation probe |
| Sellar stage | Endoscope 0°, 30°, 45°, Length 18, 30cm Diameter 4mm, 2.7mm External sheath and irrigation system and anti-fog ± Reversed Endoscope version | Cappabianca set Bipolar diathermy ± Navigation probe |
| Reconstruction Stage | Endoscope 0°, Length 18cm, Diameter 4mm External sheath and irrigation system and anti-fog | Nasal endoscopy set |
Table 2.
Summary of instruments required for different surgical stages.
10.7 Positioning and scrubbing
The authors advise instillation of decongestant nasal drops (oxymetazoline) 7days before surgery, three times a day.
It is recommended by some surgeons to be used the night before surgery and the day of surgery before taking the patient to the theater [14].
The position of the patient on operating table is supine in the reverse Trendelenburg position, hips and knees are slightly flexed, and the trunk is elevated 20 degrees [14]. Head of the patient is neutral, with a horse shoe head holder. The bridge of the nose is horizontal, parallel to the floor, and the head is turned 15 degrees toward the surgeon. When neuronavigation is used a three pin head rest or a band are fixed [41, 42].
The endotracheal tube is fixed to the lower jaw at the left side, nasogastric tube is optional, it helps in aspiration of blood and secretions before endotracheal tube extubation.
Lumbar drain may be inserted in patients having a large tumor with a considerable suprasellar extension, but this is not routine with controversy [39]. No lumbar drain was inserted for any of the patients operated by the authors.
A urine catheter is mandatory to monitor output, not only during surgery, but more significantly during the postoperative period to diagnose diabetes insipidus.
For antisepsis, betadine-soaked cotton patties are inserted in nasal cavities after positioning of the patient [39].
The patient is then draped leaving only the nostrils exposed, Suction tubes and cables including camera, light and irrigation cables are tied and placed on the left side of the patient or on a table to have a free surgical field.
Surgical stages description:
10.7.1 Nasal stage
Endoscopic examination of the nose is performed using 0 degree endoscope, usually insertion of the endoscope at the level of the floor is limited by the enlarged head of inferior turbinate (IT).
Decongestion of the inferior turbinate is done by insertion of cotton patties immersed in diluted adrenaline solution 1 in 200,000 and or oxymetazoline, sometimes infusion with diluted adrenaline solution 1 in 500,000 is required in grossly enlarged IT, in the latter case, inhalation of anesthetic like halothane if in use, should be withdrawn to prevent occurrence of arrythmia.
Landmarks are ascertained on endoscopic examination of the nose bilaterally, these are inferior turbinate, middle turbinate, choana, eustachian tube, vomer, and sphenoid sinus ostium.
In most cases, out fracture of middle turbinate is required for visualization and instrumentation, it is pushed by a blunt dissector laterally against its’ second part preserving the mucosa and avoiding a flail (hypermobile) middle turbinate, if this happened partial resection of the lower half of it is advised while keeping the axilla intact.
Natural ostium of sphenoid sinus is located between superior turbinate and nasal septum, occasionally a supreme turbinate is present, in this case, the ostium lies between the supreme turbinate and nasal septum, it is apparent in most cases, seldomly not obvious, where gentle probing at its expected site reveals it. To double check the sphenoid sinus ostium, it is approximately 1.1–1.5cm above choanal arch. The navigation is very helpful in certain anatomical variants e.g. conchal and presellar sphenoid.
Harvesting a nasoseptal flap is performed as early as this stage. Identification of sphenoid sinus ostium is a prerequisite to fashioning this flap, it is Pedicled on the nasoseptal artery, this artery is a branch of the posterior septal artery that branches from the sphenopalatine artery, the latter originates from the maxillary artery [43].
A standard flap is made up of two parallel lines, the inferior line is over the maxillary crest and the superior line is 1–2cm below the superior aspect of the nasal septum to spare the olfactory epithelium. The two lines are joined anteriorly by a vertical incision. Posteriorly the two incisions are not parallel, they rather fan from the sphenoid sinus opening superiorly and from the arch of the choana inferiorly, in this fashion the pedicle of the flap is preserved with its’ blood supply (NSA) [44]. It is illustrated in Figure 12.
The flap is composed of mucoperichondrium anteriorly and mucoperiosteum posteriorly. The nasoseptal artery crosses from the lateral nasal wall to the septum passing in a coronal line that is midway between lower lip of sphenoid sinus ostium and arch of the choana. A viable flap with intact blood supply requires both a subperiosteal and subperichondrial plane of dissection throughout the whole length of the flap, and an intact mucoperiosteum in the area between arch of the choana and sphenoid sinus ostium. A unilateral flap is elevated from the right side. In an accidental tear of the flap, a left flap can be harvested, one flap is adequate for reconstruction of the skull base in pituitary macroadenoma.
The flap is then placed in the nasopharynx and protected by a nasal pack that is placed inferiorly to occlude the choana, it is kept (stored) until the stage of reconstruction.
In the left nostril, middle turbinate is out fractured, and sphenoid sinus ostium is identified. A vertical incision is made on the posterior part of nasal septum with elevation of mucoperiosteum, the latter is removed by micro-debrider as far posterolateral as sphenoid sinus ostium, the vomer and face of sphenoid bone are exposed.
Posterior septectomy is then performed. The vomer is thin in females compared to males; a blunt dissector easily penetrates through and through, Posterior one-third of the nasal septum is removed by a backbiter to allow for bi-nostril instrumentation. By removal of the posterior part of vomer ends the nasal stage.
10.7.2 Sphenoid stage
The sphenoid ostia are enlarged medially and inferiorly and a “V”-shaped, wide anterior sphenoidotomy is performed [45, 46] The vomer remnant is drilled and the rostrum of the sphenoid sinus is removed [45].
Sphenoidotomy extends from the superior limit of the sphenoid siuns ostium (SO) superiorly to the pterygo-sphenoid synchondrosis/vidian canal at 5 and 7 O’Clock position. By drilling the sphenoid face with these landmarks, the planum sphenoidale, the optico-carotid recess, and the optic protuberances are all well visualized. Laterally it extends to the crest marking the junction of the sphenoid and ethmoid sinuses. A space below the sellar floor should be created to allow free manipulation [45, 46]. Some times it is necessary to extend drilling inferiorly at 6 O’Clock down to clival septum.
The operative space can be further widened by performing posterior ethmoidectomy, this space accommodates the scope, which is named as the cavity and a half technique [47].
When sphenoidotomy is complete, the remaining segment of the vomer demarcates the midline of sellar floor, and the two bulges of carotids are well identified.
At the end of sphenoidotomy, the midline is identified by visualizing the remaining segment of the rostrum (vomer) inferiorly and the middle of the two carotid bulges. The second surgeon then holds the endoscope and acts as a navigator.
10.7.3 Sellar stage
Throughout this stage hemostasis is very important to have a clear surgical field, to visualize important structures and prevent their injury. Sellar floor is drilled out, and a diamond or coarse diamond burr of 3 or 4mm is used. Low-speed controlled drilling is performed until the floor is as thin as an eggshell. The thinned sellar floor is then broken with a fine spade dissector or a Kerrison number-1 punch [47]. The authors use mushroom punch when available for this step instead of Kerrison punch.
By pressing the sellar dura gently, an estimate of lateral bone removal can be made. Sellar floor and anterior wall are removed millimeter by millimeter circumferentially till four blue lines are seen, superiorly and inferiorly the inter-cavernous sinuses, and laterally the cavernous sinuses) [47].
Firm tumors with suprasellar extension and a dumbbell configuration require an extended approach; in addition to the previously described sphenoidotomy, the tuberculum sellae, planum sphenoidale, and the medial optico-carotid recess are all removed with or without transdiaphragmatic dura opening [48, 49].
Opening of the dura is done in different ways, the rational is to have good surgical access with preservation of the dura, a vertical linear incision with crossed extensions, a cruciate incision which is the preference of the authors, or two vertical incisions joined by a transverse cut (H shaped).
10.7.3.1 Piecemeal tumor removal
A clear surgical field is crucial to perform safe and effective surgery. This is achieved by good hemostasis and saline irrigation; a clear field will allow good visualization. The endoscope enables an accurate detailed view, with step-by-step dissection, choosing appropriate size and good visualization of the tip of the instrument, avoiding blind dissection and traction, these measures prevent injury of the important structures; internal carotid artery, optic chiasm/nerves, suprasellar cistern, cavernous sinus, and normal pituitary gland.
The tumor should first be mobilized free in a piecemeal manner, and then gently grasped without traction in a holding forceps of appropriate size. Starting with the basal and posterior part of the tumor, it is removed in a posterior trajectory toward the clivus-dorsum sellae junction in a caudal to rostral direction [41, 45].
Next the lateral portion of the tumor is removed with the upward-angled curettes, lateral curettes are preferred to be used by the authors in clockwise and anticlockwise directions, and a plane of dissection is then created. Lastly, the superior portion of the tumor is removed after making an upward dura cut if required. Tumor decompression is done with a bimanual dissection-curette in the right hand and the suction in the left as in Figure 13; or utilizing the double suction method, where the left suction retracts the dura up, and the right suction sucks the tumor [46]. This results in progressive descent of the suprasellar tumor, which is then continuously removed concentrically. The normal pituitary gland is identified as a thinned-out, pinkish, firm tissue plastered to the diaphragma sella and is preserved. While approaching the cavernous sinus medial wall extension of the tumor, the space between the posterior clinoid and the carotid siphon (the reverse S contour) represents an ideal entry point for the removal of tumor from the posterior segment of the cavernous sinus [46]. Bleeding from the cavernous sinuses is controlled with surgical and or gelfoam.
Identification of internal carotids, optic chiasm, and normal pituitary is the safest way to prevent accidental injury. Suprasellar cistern injury infrequently happens leading to CSF leak, this should be detected intraoperatively to reconstruct appropriately.
10.7.3.2 Visualization
At the end of tumor dissection, visualization of tumor bed is very important in searching for a possible residue, an angled endoscope is used, 30 degrees or 45 degrees.
The diaphragma sellae is pushed upwards by cotton patties to expose hidden areas, if the residual tumor is seen, it is dissected from the recess using a curved suction/curette [41, 45]. The angled endoscope is positioned at 6 O’Clock, while the instruments are passed above the endoscope.
The technique is by advancing the angled endoscope close to the target, for accurate visualization, then withdrawing the endoscope while advancing the dissecting instrument gently under vision in a harmonic dynamic fashion [16, 17].
Lastly, the sella is inspected (360 degrees) in a clockwise fashion, starting at 6 O’Clock, and the cavernous sinuses are inspected during endoscope rotation. Figure 14(A–C).
The fact that only 10% of remnant of normal pituitary gland is enough for normal function, makes preservation of the gland a relatively easy step, it appears as a pinkish tissue that is more adherent than adenoma tissue, the site of which is anticipated according to MRI study preoperatively [41, 46].
Finally, the last remaining piece of the tumor is usually located at the insertion of the pituitary stalk [3].
The most common sites that accommodate the residual tumor are under the upper anterior lip of the dura at the level of the anterior cavernous sinus and the angle between optic nerve and carotid artery at the medial optico-carotid recesses [41, 46].
10.7.3.3 Reconstruction stage
The rationale beyond reconstruction is to make a watertight seal that prevents cerebrospinal fluid (CSF) leak, ascending infection, and pneumocephalus. This is achieved by a multilayered repair with fat, fascia or septal cartilage, tissue glue or histocryl, and nasoseptal flap.
Haddad and Bassagasteguy’s described the nasoseptal flap in 2006, this flap was a landmark in anterior skull base reconstruction as it is regarded as the workhorse for reconstruction in this region. This flap is the most versatile for reconstruction as it reduces morbidity significantly [50]. The greatest advantage of the nasoseptal flap is the reduction of CSF leak rate. At the beginning of endoscopic endonasal approach, before the advent of the nasoseptal flap, CSF leak rate was 24%, however, CSF leak was much reduced to 3% when nasoseptal flap was utilized in reconstruction according to recent studies [51]. Description of anatomy of the nasoseptal flap, harvesting, and its blood supply is described earlier in this chapter within the nasal stage.
10.7.3.4 Reconstruction steps
Valsava maneuver is performed after tumor resection to check for CSF leak [35, 45]. The first step in reconstruction is filling the tumor cavity with abdominal fat routinely, this prevents CSF leak from delayed rupture of the arachnoid and prevents empty sella syndrome [35].
In case of cerebrospinal fluid leak, the sella may be repaired by fat graft, and making sure that the fat graft is pulsating. An overzealous sellar packing should be avoided [41].
At the level of the dura and deep to osteal defect, a piece of surgicel or facia lata is placed to seal dural incision, in few cases operated on by the authors, a piece of fashioned septal cartilage is placed to tuck in under bony edges, in one case it acted as a trapdoor leading to pneumocephalus, so cartilage when used should be carefully positioned. On top of that plane, tissue glue or histocryl is applied, if hisocryl is used, a piece of surgicel is placed. The last layer of reconstruction is the nasoseptal flap, it is delivered from the nasopharynx, where it had been stored, and extended to cover generously the skull base. If histocryl is used before applying the nasoseptal flap as shown in Figure 15, they should be separated by surgical or thinned gelfoam, because necrosis of nasoseptal flap will happen if it is in direct contact with the histocryl.
Mechanical support of nasoseptal flap is achieved by application of gelfoam on top of it, as gelfoam swells, it gently pushes the nasoseptal flap in place. Middle turbinates are then medialized to maintain patency of osteomeatal complex and hence sinus drainage. Nasal packs are optional, it is the authors’ routine to apply bilaterally ventilated nasal packs.
11. Emergence from anesthesia
At the end of surgery, the following procedures are performed, removal of pharyngeal packs, suction of oral cavity, extubation of endotracheal tube after regaining spontaneous breathing and reflexes. The patient’s hemodynamic state should be stabilized. Coughing and straining should be kept to minimum, as both can cause CSF leak, hemorrhage, and dislodgement of nasal packs [28].
11.1 Immediate postoperative care
Care at the end of surgery includes airway management, adequate analgesia, fluid balance control, and endocrine and neurological assessment. Diabetes insipidus and pan hypopituitarism are commonly encountered. Deficiencies in any pituitary hormone must be adequately replaced besides glucocorticoids, this most frequently involves thyroid hormone. Any neurological signs, for example, cranial nerve palsy or visual change should be diagnosed early with further evaluation by imaging or re-exploration.
Diabetes insipidus (DI) if developed, occurs within the first 24hours postoperatively, this happens when more than 80% of neurons producing vasopressin are destroyed or functionally impaired. Nearly 25% of patients develop transient diabetes insipidus lasting for several days to weeks. In about 0.5% of patients, diabetes insipidus remains permanent [28, 52, 53].
All patients require long-term follow-up with an endocrinologist to assess their hormonal status.
12. Complications
Although transnasal endoscopic pituitary surgery is relatively safe, complications that may develop are serious and some are life-threatening. The complications are related to the preoperative state of the patient e.g., comorbidity and intraoperative events, they are major and minor, acute or long-term.
Immediate post-operative complications are diabetes insipidus (DI), CSF leak, and epistaxis, in that order of frequency, less frequent are endocrine, infection, cardiovascular, and pulmonary. Renal failure and shock are rare, reported complications [54]. Panhypopituitarism and nasal dryness are long-term complications. Management of complications is by a team of endocrine, anesthesia/ICU, and surgery, some complications require urgent surgical intervention e.g. signs of intracranial hemorrhage, vision deterioration, or intractable epistaxis.
12.1 Epistaxis
Epistaxis, when intractable in the immediate postoperative period, requires a return to the operating room to manage rapid loss, control bleeding by electrocautery, and verify the possibility of intracranial hemorrhage, in the latter event revision of surgery is mandatory.
In a series of 557 endoscopic pituitary surgery, posterior nasal septal artery (NSA) was the most common bleeding source of severe postoperative epistaxis following endoscopic transnasal pituitary surgery. To prevent injury of NSA, incision of the septal mucosa should not be extended downward excessively [55]. lowering of sphenoid rostrum should not exceed 5mm below the lower lip of natural sphenoid sinus ostium, and intraoperative hemostasis should be ensured by bipolar electrocoagulation.
Minor epistaxis from nasal mucosa cut edges, or when unidentified is usually managed by anterior nasal packing, other measures are; the use of intranasal hemostatic agents, or office cauterization in delayed epistaxis that can happen up to 3weeks postoperatively [56].
12.2 CSF leak
The incidence of postoperative CSF Leak after endoscopic treatment of pituitary adenoma is between 0.5% and 14% [57, 58]. The risk of developing CSF leak is associated with intrinsic patient factors with statistical significance, these are: age more than 65years, male, body mass index more than 25, and multiple comorbidities. The prevalence of CSF leaks was not associated with expertise availability, hospital stay, volume of operations in the institute, and teaching status: whether it is a teaching hospital or not [59, 60].
Treatment of CSF leak: For the management of CSF rhinorrhoea after transsphenoidal surgery, procedures using fibrin glue, gelatin gelfoam, and autologous fat graft are effective [61].
Conservative measures by reducing straining and coughing are important. Controversy exists regarding lumbar puncture in management of CSF leak, as an adjunct to surgical repair; it is not favorable by the authors as it carries a risk of meningitis. Prevention of CSF leaks is by identification of leaks intraoperatively and sellar floor reconstruction [62].
12.3 Diabetes insipidus
Diabetes insipidus (DI) is a common complication after transnasal endoscopic pituitary surgery. It has been reported that the incidence of DI after TEPS is 0.9%–36.1% [63]. During tumor resection, injury of the neurons that produce and transport vasopressin (magnocellular neurons) lead to DI, these neurons form the hypothalamo-hypophyseal tract leading to a transient or permanent imbalance in water homeostasis [64].
Nayak et al. [65] found that tumor size, suprasellar extension, and preoperative visual abnormalities are significantly correlated with the postoperative DI (
Transient DI typically occurs within 24–48hours after the operation and usually remits spontaneously within 3–5days [67, 68].
Patients are diagnosed with DI and treated with desmopressin (1-diamino-8-arginine vasopressin) when urine output is less than 5mL/kg/hr. With a serum sodium concentration of more than 145mmol/L or an increase of more than 3mmol/L in serum sodium concentration between two consecutive tests after surgery. DI is considered permanent if medical treatment is required for more than 6months after surgery [66].
13. Current study
13.1 Objectives
A pilot study was conducted to investigate the demographic data, clinical presentation, surgical management, and complications of pituitary tumors in a single center in Khartoum.
13.2 Methodology
This is a retrospective, analytic, hospital-based study. Conducted in Ribat University Hospital, Neuro Spine Center, Khartoum, Sudan. From November 2017 to March 2023.
Study subjects: Patients presented to the outpatient department with symptoms and signs of sellar pathology and upon radiological assessment have evidence of pituitary tumor, or patients referred from: ophthalmology department with vision affection, endocrine department with abnormal hormone profile, or obstetrics and gynecology department with infertility. A multidisciplinary team evaluated the patients by clinical, radiological, laboratory and detailed ophthalmological assessment, the team consists of members from the following departments: neurosurgery, ophthalmology, endocrinology, otolaryngology, radiology, anesthesiology, and ICU. Oncology and Obstetrics and gynecology were often required. The plan of management was then set for each patient, including a lifelong follow up plan.
Inclusion criteria: Patients with pituitary tumors that were proven radiologically and performed assessment by the multidisciplinary team. Patients who underwent transnasal endoscopic pituitary surgery according to the decision of the team, with the indications mentioned in this text.
Exclusion criteria: patients with sellar lesions other than pituitary tumors, e.g., chordoma, craniopharyngioma, meningioma…etc. and patients planned for external (craniotomy) approach.
A data sheet was used to collect the information.
Surgical procedure: A transnasal endoscopic pituitary surgery was performed according to the described technique and details mentioned in the surgical section earlier.
13.3 Results
A total of 162 patients were included in this study, 150 were pituitary adenoma, and 12 patients were other pathologies: three meningioma, one retroclival epidrmoid cyst, 6 craniopharyngioma, one arachnoid cyst, and one fungal granuloma.
The ages ranged between 19 and 76years. Males and females were almost equal. Regarding the clinical presentation, vision impairment was the leading, it was reported in 137 patients (91%), 6 patients (4%) presented with acromegaly, due to excessive growth hormone production, and 7 patients (4.6%) with hyperprolactinemia. Three patients (2%) presented with apoplexy. Tumor extension according to MRI: 25 (17%) tumors were confined to the sella and 125 (83%) tumors extended to supra and/or parasellar regions. During the COVID-19 pandemic, as recommended by most of the guidelines to cease elective surgeries, only two emergency patients were operated on, one presented with apoplexy, was a young general surgeon, presented with severe headache and acute failing vision for 2days, surgery was performed after 24hours only of presentation, his vision was saved immediately postoperatively and his career so. The second emergency patient presented with hydrocephalus, he required external ventricular drainage before endoscopic transnasal surgery.
The operative time at the beginning was an average of 6hours, it decreased to 2.5hours after 3years from the beginning, however, surgery was lengthened in tumors with suprasellar and parasellar extension even lately.
Complications were: diabetes insipidus in 6 patients (4%), in five of them DI was transient, CSF leak that required re-exploration and reconstruction was reported in 3 patients (2%), tension pneumocephalus and CSF leak in one patient (0.7%), chest infection in one patient, superior sagittal sinus thrombosis in one patient as shown in Figure 16. Visual symptoms improved in 128 patients (93%), and the remaining 9 patients who showed no improvement in vision, their vision were affected for more than 6months when surgery was performed. Panhypopituitarism was reported in one patient. The mortality rate is 2% (3 patients), one intraoperative death due to massive uncontrolled bleeding (25years male), one DI and one died of aspiration pneumonia postoperatively.
Three patients required revision surgery for tumor recurrence. One patient required a planned external approach after endoscopic transnasal resection, while two patients had symptomatic and radiological tumor recurrence. No reported vision deterioration, persistent anosmia, or internal carotid injury.
Gross tumor resection and outcome of surgery are still under prospective study and will be reported somewhere else.
13.4 Discussion
In the current study, a variety of lesions were encountered in the sellar region, reflecting the variety of anatomical structures at histological level, and diversity of embryological origin, apart from pituitary adenoma, lesions included meningioma, chordoma, craniopharyngioma. One case was found to be fungal granuloma which extended from the sphenoid sinus, mimicking pituitary adenoma, an important differential diagnosis. Lesions of the sellar region present as early as childhood, for example, craniopharyngioma, it is not uncommon, where six cases of craniopharyngioma were diagnosed among the studied patients. Radiological findings are a very important tool for making preoperative diagnosis of lesions other than pituitary adenoma, a neuroradiologist is an important team member, where expertise and opinion are very crucial in preoperative diagnosis, and hence management plan, a combined multidisciplinary discussion, at the time of deciding the plan of management has great input.
In low-resource countries where there is paucity of medical services, as the authors experience, most of the patients are referred from ophthalmology departments with visual complications, where adenoma is huge in size, Figure 3, demonstrates adenoma on MRI pushing the optic chiasm.
The majority present with large or giant tumors upon radiological assessment with suprasellar and parasellar extensions.
One patient presented with hydrocephalus because the tumor was enormous to the extent that it extended superiorly leading to obstruction of the third ventricle as the patient was initially managed by external ventricular drainage, and then scheduled for elective endoscopic pituitary resection. This patient reflects the advanced clinical manifestations of pituitary adenoma in the studied series.
Elective endoscopic transnasal surgeries were recommended to be paused during the COVID 19 era [69], during that period elective transnasal endoscopic pituitary surgeries were postponed.
One of the three apoplexy patients was a doctor, he presented with severe headache for 2days, and had deterioration in vision for 1day, otherwise, he was dealing a normal life, with no significant medical history, upon MRI brain, pituitary macroadenoma was detected, within the next 24hours of presentation, he was thoroughly investigated, where it was a nonfunctioning adenoma, vision impairment started the second day of headache, this signifies that hemorrhage was progressive and hematoma was rapidly increasing in size, he was operated on within 24hours, and showed immediate improvement in vision and headache in the postoperative period. This case is another example of an emergency pituitary surgery.
The learning curve of endoscopic transnasal pituitary surgery was obvious and well demonstrated by the reduction of operative time to almost one-third. This is achieved by the acquisition of surgical skills, catching surgical tips and tricks, and forming harmony between operating team members. With experience more complicated cases are operated on, these include parasellar and suprasellar tumors, meticulous dissection of these tumors requires a longer duration, to avoid injury of the neighboring structures, namely the carotids, optic chiasm, optic nerve, cavernous sinus, cistern, and normal pituitary gland, special technique is advocated and described earlier in the surgical section. Utilization of angled endoscopes improves surgical field exposure and is anticipated to minimize the frequency of residual tumors.
The safest and cheapest way to avoid complications is by adequate knowledge of the detailed anatomy, anatomical variations, and surgical landmarks. Image guidance (neuro-navigation) is used to identify the bony landmarks, it is important especially when anatomical variations are present, nevertheless, it is not a substitute for knowledge, it is rather an adjunct, that helps increase safety and reduce operative time. Because our hospital is a limited facility, neuro-navigation is not provided routinely, we depend mainly on knowledge of anatomy and surgical skills.
In this study, four patients out of 150 cases required surgical intervention, with a rate of CSF leak of 2.7% only, this low rate is most likely due to the reconstruction multilayer protocol which is described earlier; two important layers are abdominal fat and nasoseptal flap, both are used routinely in reconstruction during primary surgery.
One patient developed CSF leak and deterioration in the level of consciousness after a smooth and full recovery from anesthesia, 12 hours postoperatively, on MRI, tension pneumocephalus was demonstrated. Generally in reconstruction as mentioned earlier, multilayers are used, at the level of the osteal defect of the sellar floor, fashioned septal cartilage is used, and tucked in beneath the bony edges of the sella, in this particular patient the cartilage acted as a trapdoor allowing the escape of CSF and permitting air to enter simultaneously, this patient required emergency revision and reconstruction, he improved clinically and radiologically and was discharged from the ICU 3 days later. This case is a good example of the importance of early emergence from anesthesia, where neurological signs are indicative of intracranial complications. Panhypopituitarism was reported in one patient, but due to missing data, as this is a pilot study, a future prospective study, is expected to report hypopituitarism among patients more frequently.
One patient developed superior sagittal thrombosis in the postoperative period. This complication was reported in a revision case with endoscopic transnasal surgery [70].
14. Conclusion
Pituitary tumors present with ophthalmic and compression effects, these include vision impairment and hydrocephalus, while nonfunctioning adenoma present with excess hormone production, other sellar pathologies are frequently encountered, these include meningioma, craniopharyngioma, and arachnoid cyst. Pituitary tumors occur in a wide age range, Acute hemorrhage in pituitary adenoma presents with severe headache and acute failing vision, in the current study it was reported in 2% of patients. Radiological investigations are important for preoperative diagnosis and planning and image-guided monitoring is advocated as routine or at least for patients with unfavorable anatomical variations.
Endoscopic transnasal pituitary surgery nowadays is the gold standard surgery for most pituitary tumors even those with sellar and suprasellar extension, the endoscope has greatly revolutionized pituitary surgery, being minimally invasive and giving superlative visualization of the surgical field when compared to the microscope, especially the corners, furthermore, angled endoscopes display hidden recesses at the tumor site clearly. On the other hand, the learning curve of endoscopic transnasal approach is a steep curve. With experience, the operative time is reduced, surgical outcome is improved, complications are decreased, and more extensive pathology is dealt with. Perioperative management requires a team approach from different specialties related to pituitary pathology. Indications of urgent surgery are apoplexy and hydrocephalus.
Complications of transnasal endoscopic surgery encountered in this study are CSF leak, diabetes insipidus, pneumocephalus, aspiration pneumonia, superior sagittal thrombosis, and death. Vision improvement is not expected when surgery is delayed. Gross tumor resection and revision surgery need to be verified with a detailed longitudinal study.
References
- 1.
Ganapathy MK, Tadi P. Anatomy, Head and Neck, Pituitary Gland. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/nbk551529/ - 2.
Chin BM, Orlandi RR, Wiggins RH. Evaluation of the sellar and parasellar regions. Magnetic Resonance Imaging Clinics of North America. 2012; 20 (3):515-543 - 3.
Larkin S, Ansorge O. Development and Microscopic Anatomy of the Pituitary Gland. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. MDText.com, Inc., South Dartmouth (MA): 2017 - 4.
Yamash*ta S, Resende LA, Trindade AP, Zanini MA. A radiologic morphometric study of sellar, infrassellar and parasellar regions by magnetic resonance in adults. Springerplus. 2014; 3 :291 - 5.
Ceylan S, Anik I, Koc K, Kokturk S, Ceylan S, Cine N, et al. Microsurgical anatomy of membranous layers of the pituitary gland and the expression of extracellular matrix collagenous proteins. Acta Neurochirurgica. 2011; 153 (12):2435-2443 discussion 2443 - 6.
Ilahi S, Ilahi TB. Anatomy, Adenohypophysis (Pars Anterior, Anterior Pituitary). Treasure Island (FL): StatPearls Publishing; 2022 - 7.
Go JL, Rajamohan AG. Imaging of the sella and parasellar region. Radiologic Clinics of North America. 2017; 55 (1):83-101 - 8.
Lechan RM, Toni R. Functional Anatomy of the Hypothalamus and Pituitary. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Mdtext.com, Inc.; South Dartmouth (MA): 2016 - 9.
El Sayed SA, Fahmy MW, Schwartz J. Physiology, Pituitary Gland. Treasure Island (FL): StatPearls Publishing; 2023 - 10.
Ooi GT, Tawadros N, Escalona RM. Pituitary cell lines and their endocrine applications. Molecular and Cellular Endocrinology. 2004; 228 (1–2):1-21 - 11.
Fujimoto M, Takeuchi K, Sugimoto M, Maruo T. Prevention of postpartum hemorrhage by uterotonic agents: Comparison of oxytocin and methylergometrine in the management of the third stage of labor. Acta Obstetricia et Gynecologica Scandinavica. 2006; 85 (11):1310-1314 - 12.
Jost A, Das MJ. Neuroanatomy, Pars Nervosa. Treasure Island (FL): StatPearls Publishing; 2022 - 13.
Perez-Castro C, Renner U, Haedo MR, Stalla GK, Arzt E. Cellular and molecular specificity of pituitary gland physiology. Physiological Reviews. 2012; 92 (1):1-38 - 14.
Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr. Atypical pituitary adenomas: Incidence, clinical characteristics, and implications. Journal of Neurosurgery. 2011; 114 :336-344 - 15.
Al-Shraim M, Asa SL. The 2004 World Health Organization classification of pituitary tumors: What is new? Acta Neuropathologica. 2006; 111 :1-7 - 16.
Theodros D, Patel M, Ruzevick J, Lim M, Bettegowda C. Pituitary adenomas: Historical perspective, surgical management and future directions. CNS Oncology. 2015; 4 (06):411-429 - 17.
Hardy J. Transphenoidal microsurgery of the normal and pathological pituitary. Clinical Neurosurgery. 1969; 16 :185-217 - 18.
Molitch ME. Diagnosis and treatment of pituitary adenomas: A review. Journal of the American Medical Association. 2017; 317 (5):516-524 - 19.
Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, et al. Pituitary incidentaloma: An endocrine society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism. 2011; 96 (4):894-904 - 20.
Ferrante E, Ferraroni M, Castrignanò T, Menicatti L, Anagni M, Reimondo G, et al. Non-functioning pituitary adenoma database: A useful resource to improve the clinical management of pituitary tumors. European Journal of Endocrinology. 2006; 155 (6):823-829 - 21.
Ogra S, Nichols AD, Stylli S, Kaye AH, Savino PJ, Danesh-Meyer HV. Visual acuity and pattern of visual field loss at presentation in pituitary adenoma. Journal of Clinical Neuroscience. 2014; 21 (5):735-740 - 22.
Steiner E, Wimberger D, Imhof H, Knosp E, Hajek P. Gd-DTPA in the MR diagnosis of pituitary adenomas. Rofo. 1989; 150 (3):323-327 - 23.
Kucharczyk W, Bishop JE, Plewes DB, Keller MA, George S. Detection of pituitary microadenomas: Comparison of dynamic keyhole fast spin-echo, unenhanced, and conventional contrast-enhanced MR imaging. AJR. American Journal of Roentgenology. 1994; 163 (3):671-679 - 24.
Evanson J. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Radiology of the Pituitary. South Dartmouth (MA): Mdtext.com, Inc.; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/nbk279161/ - 25.
Russ S, Anastasopoulou C, Shafiq I. Pituitary Adenoma. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/nbk554451/ - 26.
Bhimani AD, Schupper AJ, Arnone GD, Chada D, Chaker AN, Mohammadi N, et al. Size matters: Rethinking of the sizing classification of pituitary adenomas based on the rates of surgery: A multi-institutional retrospective study of 29,651 patients. Journal of Neurological Surgery Part B: Skull Base. 2020; 83 (1):66-75. DOI: 10.1055/s-0040-1716673 - 27.
Horvat A, Kolak J, Gopčević A, Ilej M, Gnjidić Ž. Anesthetic management of patients undergoing pituitary surgery. Acta Clinica Croatica. 2011; 50 :209-216 - 28.
Burton CM, Nemergut EC. Anesthetic and critical care management of patients undergoing pituitary surgery. Frontiers of Hormone Research. 2006; 34 :236-255 - 29.
Duz B, Harman F, Secer HI, Bolu E, Gonul E. Transsphenoidal approaches to the pituitary: A progression in experience in a single centre. Acta Neurochirurgica. 2008; 150 :1133-1138 - 30.
Jagannthan J, Laws ER, Jane JA Jr. Advantages of endoscopic approach and transitioning from microscope to the endoscope for endonasal approaches. In: Kassam AB, Gardner PA, editors. Endoscopic Approaches for Skull Base. Basel, Switzerland: S. Karger AG; 2012. pp. 7-20 - 31.
Musleh W, Sonabend AM, Lesniak MS. Role of craniotomy in the management of pituitary adenomas and sellar/parasellar tumors. Expert Review of Anticancer Therapy. 2006; 6 (Suppl 9):S79-S83. DOI: 10.1586/14737140.6.9s.S79 - 32.
Salama MM, Rady MR. Transcranial approaches for pituitary adenomas: Current indications and clinical and radiological outcomes. Egyptian Journal of Neurosurgery. 2021; 36 :21. DOI: 10.1186/s41984-021-00117-x - 33.
Ojha BK, Husain M, Rastogi M, Chandra A, Chugh A, Husain N. Combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic decompression of a giant pituitary adenoma: Case report. Acta Neurochirurgica. 2009; 151 (7):843-847; discussion 847. DOI: 10.1007/s00701-009-0336-z Epub 2009 Apr 28 - 34.
Leach P, Abou-Zeid AH, Kearney T, Davis J, Trainer PJ, Gnanalingham KK. Endoscopic transsphenoidal pituitary surgery: Evidence of an operative learning curve. Neurosurgery. 2010; 67 :1205-1212 - 35.
O’Malley BW Jr, Grady MS, Gabel BC, Cohen MA, Heuer GG, Pisapia J, et al. Comparison of endoscopic and microscopic removal of pituitary adenomas: Single-surgeon experience and the learning curve. Neurosurgical Focus. 2008; 25 :E10 - 36.
Huang J, Hong X, Cai Z, Lv Q, Jiang Y, Dai W, et al. The learning curve of endoscopic endonasal transsphenoidal surgery for pituitary adenomas with different surgical complexity. Frontiers in Surgery. 2023; 10 :1117766. DOI: 10.3389/fsurg.2023.1117766 - 37.
Okuda T, Kataoka K, Kato A. Training in endoscopic endonasal transsphenoidal surgery using a skull model and eggs. Acta Neurochirurgica. 2010; 152 :1801-1804 - 38.
Sharma BS, Sawarkar DP, Suri A. Endoscopic pituitary surgery: Techniques, tips and tricks, nuances, and complication avoidance. Neurology India. 2016; 64 :724-736 - 39.
Cappabianca P, Cavallo LM, de Divitiis E. Endoscopic endonasal transsphenoidal surgery. Neurosurgery. 2004; 55 :933-940 - 40.
Cavallo LM, Dal Fabbro M, Jalalod’din H, Messina A, Esposito I, Esposito F, et al. Endoscopic endonasal transsphenoidal surgery. Before scrubbing in: Tips and tricks. Surgical Neurology. 2007; 67 :342-347 - 41.
Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: A systematic review. Cancer. 2004; 101 :613-619 - 42.
Laws ER Jr, Lopes MB. The new WHO classification of pituitary tumors: Highlights and areas of controversy. Acta Neuropathologica. 2006; 111 :80-81 - 43.
Jho HD, Alfieri A. Endoscopic endonasal pituitary surgery: Evolution of surgical technique and equipment in 150 operations. Minimally Invasive Neurosurgery. 2001; 44 :1-12 - 44.
Sigler AC, D’Anza B, Lobo BC, Woodard TD, Recinos PF, Sindwani R. Endoscopic skull base reconstruction: An evolution of materials and methods. Otolaryngologic Clinics of North America. 2017; 50 (3):643-653 - 45.
Reuter G, Bouchain O, Demanez L, Scholtes F, Martin D. Skull base reconstruction with pedicled nasoseptal flap: Technique, indications, and limitations. Journal of Cranio-Maxillo-Facial Surgery. 2019; 47 (1):29-32 - 46.
Lucas JW, Zada G. Endoscopic surgery for pituitary tumors. Neurosurgery Clinics of North America. 2012; 23 :555-569 - 47.
Kassam A, Snyderman CH, Mintz A, Gardner P, Carrau RL. Expanded endonasal approach: The rostrocaudal axis. Part I. Crista galli to the sella turcica. Neurosurgical Focus. 2005; 19 :E3 - 48.
Kassam AB, Gardner PA, Prevedello DM, Snyderman CH, Carrau RL, Zhao B. Principles of endoneurosurgery. In: Kassam AB, Gardner PA, editors. Endoscopic Approaches for Skull Base. Basel, Switzerland: S. Karger AG; 2012. pp. 21-26 - 49.
Sankhla SK, Jayashankar N, Khan GM. Surgical management of selected pituitary macroadenomas using extended endoscopic endonasal transsphenoidal approach: Early experience. Neurology India. 2013; 61 :122-130 - 50.
Zhao B, Wei YK, Li GL, Li YN, Yao Y, Kang J, et al. Extended transsphenoidal approach for pituitary adenomas invading the anterior cranial base, cavernous sinus, and clivus: A single-center experience with 126 consecutive cases. Journal of Neurosurgery. 2010; 112 :108-117 - 51.
Zanation AM, Carrau RL, Snyderman CH, Germanwala AV, Gardner PA, Prevedello DM, et al. Nasoseptal flap reconstruction of high flow intraoperative cerebral spinal fluid leaks during endoscopic skull base surgery. American Journal of Rhinology & Allergy. 2009; 23 (5):518-521 - 52.
Singh C, Shah N. Posterior nasoseptal flap in the reconstruction of skull base defects following endonasal surgery. The Journal of Laryngology and Otology. 2019; 133 (5):380-385 - 53.
Nemergut EC, Dumont AS, Barry UT, Laws ER. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesthesia and Analgesia. 2005; 101 :1170-1181 - 54.
Gnjidi ć Ž. Suvremeno kirurško liječenje tumora selarne regije. Lijec̆nic̆ki Vjesnik. 2004; 126 :26-31 - 55.
Al-Qurayshi Z, Bennion DM, Greenlee JDW, Graham SM. Endoscopic pituitary surgery: National database review. Head & Neck. 2022; 44 (12):2678-2685 - 56.
Liu X, Wang P, Li M, Chen G. Incidence, risk factors, management and prevention of severe postoperative epistaxis after endoscopic endonasal transsphenoidal surgery: A single center experience. Frontiers in Surgery. 2023; 10 :1203409. DOI: 10.3389/fsurg.2023.1203409 - 57.
Zimmer LA, Andaluz N. Incidence of epistaxis after endoscopic pituitary surgery: Proposed treatment algorithm. Ear, Nose, & Throat Journal. 2018; 97 (3):E44-E48 - 58.
Rotman LE, Alford EN, Davis MC, Vaughan TB, Woodworth BA, Riley KO. Preoperative radiographic and clinical factors associated with the visualization of intraoperative cerebrospinal fluid during endoscopic transsphenoidal resection of pituitary adenomas. Surgical Neurology International. 2020; 11 :59 - 59.
Cohen S, Jones SH, Dhandapani S, Negm HM, Anand VK, Schwartz TH. Lumbar drains decrease the risk of postoperative cerebrospinal fluid leak following endonasal endoscopic surgery for suprasellar meningiomas in patients with high body mass index. Operative Neurosurgery. 2018; 14 (1):66-71 - 60.
Zhou Z, Zuo F, Chen X, et al. Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: A meta-analysis and systematic review. BMC Neurology. 2021; 21 :417. DOI: 10.1186/s12883-021-02440-0 - 61.
Zhang C, Ding X, Lu Y, Hu L, Hu G. Cerebrospinal fluid rhinorrhoea following transsphenoidal surgery for pituitary adenoma: Experience in a Chinese centre. Acta Otorhinolaryngologica Italica. 2017; 37 (4):303-307. DOI: 10.14639/0392-100X-1086 - 62.
Ahn S, Park JS, Kim DH, Kim SW, Jeun SS. Surgical experience in prevention of postoperative CSF leaks using abdominal fat grafts in endoscopic endonasal transsphenoidal surgery for pituitary adenomas. Journal of Neurological Surgery Part B: Skull Base. 2021; 82 (5):522-527. DOI: 10.1055/s-0040-1712179 Epub 2020 Aug 20 - 63.
Schreckinger M, Szerlip N, Mittal S. Diabetes insipidus following resection of pituitary tumors. Clinical Neurology and Neurosurgery. 2013; 115 (2):121-126. DOI: 10.1016/j.clineuro.2012.08.009 ISSN 0303-8467. Available from:https://www.sciencedirect.com/science/article/pii/s0303846712004349 - 64.
Christodoulou E, Ma J, Collins GS, Steyerberg EW, Verbakel JY, Van Calster B. A systematic review shows no performance benefit of machine learning over logistic regression for clinical prediction models. Journal of Clinical Epidemiology. 2019; 110 :12-22. DOI: 10.1016/j.jclinepi.2019.02.004 ISSN 0895-4356. Available from:https://www.sciencedirect.com/science/article/pii/s0895435618310813 - 65.
de Vries F, Lobatto DJ, Verstegen MJT, van Furth WR, Pereira AM, Biermasz NR. Postoperative diabetes insipidus: How to define and grade this complication? Pituitary. 2021; 24 (2):284-291. DOI: 10.1007/s11102-020-01083-7 Epub 2020 Sep 29 - 66.
Oh H, Cheun H, Kim YJ, Yoon HK, Kang H, Lee HC, et al. Cephalocaudal tumor diameter is a predictor of diabetes insipidus after endoscopic transsphenoidal surgery for non-functioning pituitary adenoma. Pituitary. 2021; 24 (3):303-311. DOI: 10.1007/s11102-020-01108-1 Epub 2020 Nov 16 - 67.
Zhan R, Ma Z, Wang D, Li X. Pure endoscopic endonasal transsphenoidal approach for nonfunctioning pituitary adenomas in the elderly: Surgical outcomes and complications in 158 patients. World Neurosurgery. 2015; 84 (6):1572-1578, ISSN 1878-8750. DOI: 10.1016/j.wneu.2015.08.035. Available from:https://www.sciencedirect.com/science/article/pii/s1878875015010517 - 68.
Lobatto DJ, de Vries F, Zamanipoor Najafabadi AH, Pereira AM, Peul WC, Vliet Vlieland TPM, et al. Preoperative risk factors for postoperative complications in endoscopic pituitary surgery: A systematic review. Pituitary. 2018; 21 (1):84-97. DOI: 10.1007/s11102-017-0839-1 - 69.
Kamel R, Ragab A, Abdelghaffar H, Kaled A, Fattah AEA, Abdelaziz M, et al. Safe practice guidance: A review for otorhinolaryngologists during COVID-19 pandemic and after reopen process. Rhinology Online. 2020; 3 :128-140. DOI: 10.4193/RHINOL/20.014 - 70.
Thakur JD, Corlin A, Mallari RJ, Yawitz S, Eisenberg A, Sivakumar W, et al. Complication avoidance protocols in endoscopic pituitary adenoma surgery: A retrospective cohort study in 514 patients. Pituitary. 2021; 24 (6):930-942. DOI: 10.1007/s11102-021-01167-y Epub 2021 Jul 2
Written By
Nazik Abdullah, Haytham Osman, Honida Ibrahim, Khalid Elzein and Ali Awad
Submitted: 01 September 2023 Reviewed: 02 September 2023 Published: 07 March 2024
© The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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