[Abstract] OBJECTIVE: To summarize the experience of transsphenoidal surgery under neuronavigation for pituitary adenoma and discuss its indications.
METHODS: A retrospective analysis of 138 cases of transsphenoidal pituitary adenoma surgery under neuronavigation was performed. Indications for surgery: 36 cases of recurrent pituitary adenoma after previous transsphenoidal surgery, 45 cases of invasive pituitary adenoma, 45 cases of microadenoma located in the lateral or deep pituitary gland, 4 cases of malpneumatization of the pterygoid sinus, 3 cases of abnormal thickening of the skull base, 4 cases of bilateral internal carotid artery spacing stenosis and 1 case of nasal septal deviation.
Results: In the recurrent group, there were 12 cases of total tumor resection and 9 cases of subtotal resection, 2 cases of postoperative tumor cavity hematoma, 4 cases of cerebrospinal fluid leakage, 3 cases of combined intracranial infection, 2 cases of combined traffic hydrocephalus, 1 case of permanent actinic nerve palsy and 3 cases of hypopituitarism; 9 cases were cured and 8 cases were in remission. In the invasive group, there were 5 cases of total resection and 27 cases of subtotal resection, 1 case of cerebrospinal fluid leakage and intracranial infection and 1 case of tumor cavity hematoma after surgery; 2 cases were cured and 22 cases were in remission. All 30 cases of invasive hormone-secreting pituitary adenoma were not cured and in remission. In the microadenoma group, all 45 cases were hormone-secreting type, all of them were resected and 38 cases were cured. Four cases in the carotid artery spacing stenosis group and one in the nasal septal deviation group were all resected and cured. In the pterygoid sinus dysplasia group, 2 tumors were completely resected, 2 were subtotal resected, and 1 was cured. In the group with abnormal thickening of the skull base, there were two cases of total resection, one case of subtotal resection and one case of cure.
Conclusion: The neuronavigation can make partial transsphenoidal pituitary adenoma resection more accurate, safe and effective, expand the indications for transsphenoidal surgery to a certain extent, and can effectively avoid the radiation hazard of the operator receiving X-ray.
[Keywords] Pituitary adenoma; neuronavigation; transsphenoidal surgery.
Pituitary adenomas account for about 10%-15% of intracranial tumors. Since the application of surgical microscopy and intraoperative X-ray monitoring to transsphenoidal surgery for pituitary adenomas, surgical complications and morbidity and mortality rates have been significantly reduced, so transsphenoidal microsurgery has become the main surgical approach and surgical method for pituitary adenomas. However, in cases of poor pneumatization of the pterygoid sinus, abnormal thickening of the skull base, recurrent pituitary adenomas and narrow spacing of the internal carotid arteries, it is relatively difficult to accurately determine the midline and/or saddle base position during surgery. From January 2006 to December 2010, our department performed 138 cases of pituitary adenoma surgery with Brain Lab frameless navigator under neuronavigational transsphenoidal approach, accounting for 6.6% of all transsphenoidal pituitary adenoma surgery cases in the same period. The clinical data and surgical outcomes are reported below, and the indications for neuroguided transsphenoidal pituitary adenoma surgery and its related considerations are discussed.
Data and Methods
1. General information
There were 50 males and 88 females in this group, aged 6 to 73 years, with an average of (38±15) years, and the disease duration ranged from half a month to 30 years, with an average of (64±62) months. According to pituitary function: 41 cases of non-functional adenoma, 9 cases of prolactin (PRL) adenoma, 39 cases of growth hormone (GH) adenoma, 48 cases of adrenocorticotropic hormone (ACTH) adenoma and 1 case of thyroid stimulating hormone (TSH) adenoma. According to the tumor size, 49 cases had a maximum diameter of ≥3 cm (giant adenoma), 30 cases had a diameter of 1 to 3 cm (macroadenoma), and 59 cases had a diameter of ≤1 cm (microadenoma). According to the preoperative MRI and whether the saddle base bone and dura mater were invaded by the tumor or not, there were 59 cases with invasive tumor growth and 79 cases with non-invasive tumor growth. The indications for surgery were mainly based on clinical manifestations, pituitary function tests and radiological manifestations. The indications for surgery in this group of PRL adenomas were tumor insensitivity to bromocriptine, patient intolerance of bromocriptine side effects, or pituitary PRL microadenoma.
Reasons for using neuronavigation: 36 recurrent pituitary adenomas (including those with residual tumor growth) after transsphenoidal surgery (including 14 cases of invasive type), including 16 non-functional adenomas, 12 GH adenomas, 7 ACTH adenomas and 1 PRL adenoma; 45 invasive pituitary adenomas, including 24 non-functional adenomas, 13 GH adenomas, 6 PRL adenomas, 1 ACTH adenoma and There were 45 cases of microadenomas located in the lateral or deep pituitary gland, including 39 cases of ACTH adenoma, 5 cases of GH adenoma, and 1 case of PRL adenoma. Two cases had GH adenoma and one case each had PRL adenoma and ACTH adenoma; one case with extreme deviation of the nasal septum had GH macroadenoma. All recurrent pituitary adenomas were attributed to recurrence regardless of whether they contained other causes, and all microadenomas were attributed to the latter as long as they were combined with other causes.
2.Surgical method
The VectorVision Compact version 4.0 neuronavigation system from BrainLAB, Germany, was used as a passive infrared tracking and positioning system. A high-quality MRI flat scan + enhanced thin layer scan with a layer thickness of 1 mm was performed preoperatively to the tip of the nose. The scan data was burned to a CD-ROM and entered into the surgical planning system to mark the pituitary tumor and important anatomical structures such as the internal carotid artery, cavernous sinus, optic nerve, hypothalamus and brainstem, and to develop the surgical plan. The surgery is performed under general anesthesia with the patient in the supine position with the head secured in a Doro three-peg head frame and the navigation stent secured to the head frame or with a bandage-type navigation stent tied to the head. The surgical plan was entered into the navigation workstation, and after successful registration, further surgery was performed according to the conventional transsphenoidal approach. There were 133 cases of transsphenoidal sinus surgery through a single nostril and 5 cases of transoral pterygoid sinus surgery. 11 cases were operated with endoscopic assistance. An expanded transsphenoidal approach was used in 15 cases, all of which were invasive non-functional giant adenomas (including 5 recurrent cases). A navigation stick was used at all times during the operation to determine the direction of the operation, the position of the midline and saddle base, as well as the suprasellar, parasternal, anterior and posterior positions reached by the surgical instruments, and even the position of the incised pituitary. The operation process of the surgery itself is the same as the general transsphenoidal operation.
3.The criteria for judging the efficacy
The clinical performance, MRI examination and pituitary endocrinology examination results of patients more than 3 months after surgery are used to judge the efficacy of surgery [3, 5]. The criteria for determining the efficacy of surgery for non-functional adenoma are: cure, complete resection of tumor and normalization of visual field; remission, sub-total resection of tumor and stable size of residual tumor on postoperative follow-up; progress, >50% resection of tumor; ineffective, <50% resection of tumor. In remission, normal PRL is restored, menstruation is not restored in women, and normal low blood testosterone in men; in progress, PRL is reduced by ≥80%; invalid: PRL is reduced by <80% or not reduced and elevated. ACTH adenoma efficacy criteria: cure: clinical symptoms disappeared, 24-hour urinary free cortisol (24h UFC) ≤80μg; progress, 24h UFC reduced by ≥50%; ineffective: 24h UFC reduced by <50%. Criteria for judging the efficacy of thyrotropin adenoma: cure, normalization of blood TSH and thyroid function; progress, reduction of TSH by ≥50%; ineffective: reduction of TSH by <50%.
Results
1.Surgery situation
The operative time was 50-220 min, among which the average time for installation of navigation positioning stent and navigation registration was 17 min. 5 cases with bandage-type navigation stent showed intraoperative navigation deviation, and C-arm X-ray was used instead to monitor the direction of access, while all other cases completed the surgery accurately under neurological navigation. In the recurrent group, 12 tumors were completely resected, 9 were subtotal resected, 13 were mostly resected, and 2 were partially resected. In the group with deviated nasal septum, one tumor was completely resected.
2.Surgical complications
There were no fatal cases. There were 71 cases of transient water and electrolyte disorders after surgery, all of which were cured after treatment. There were 34 cases of intraoperative cerebrospinal fluid leakage, including 8 cases in the invasive group, 16 cases in the recurrent group, 8 cases in the microadenoma group, and 1 case each in the skull base thickening and internal carotid artery stenosis groups. There were no permanent complications in the microadenoma group, carotid artery stenosis group, skull base thickening group, pterygoid sinus pneumatization dysplasia group and nasal septal deviation group. In the group of recurrent pituitary adenoma, there were 2 cases of postoperative tumor cavity hematoma requiring reoperation; 1 case of transient actinic nerve palsy and 1 case of permanent actinic nerve palsy; 4 cases of postoperative cerebrospinal fluid leak repair, including 3 cases of combined intracranial infection and 2 cases of combined traffic hydrocephalus; 2 cases of hypoadrenocorticism and 1 case of hypothyroidism; all of these complications occurred in the group of recurrent pituitary non-functional giant adenoma All of these complications occurred in cases of recurrent non-functioning giant pituitary adenoma. In the group of invasive pituitary adenomas, there was one case of cerebrospinal fluid leakage combined with intracranial infection after surgery, and one case of reoperation for tumor cavity hematoma. Among the 15 cases of expanded transsphenoidal surgery, 2 cases of postoperative hematoma in the tumor cavity were recurrent pituitary non-functional giant adenoma.
3.Following up
All cases were followed up for 3 to 62 months, with a mean of (26.5±17.0 months). According to the analysis of pituitary function: 41 cases of non-functional pituitary adenoma, 6 cases were cured, 30 cases were in remission, 4 cases progressed, 1 case was discharged automatically due to postoperative combined hypertensive cerebral hemorrhage breaking into the ventricle and deep coma, and all other patients had different degrees of visual improvement after surgery. There were 9 cases of pituitary prolactin adenoma, 2 cases were cured, 6 cases progressed, and 1 case was ineffective. There were 39 cases of pituitary growth hormone adenoma, 6 cases were cured, 3 cases were in remission, 15 cases were improved, and 15 cases were ineffective. Adrenocorticotropic hormone adenoma 48 cases, cured in 39 cases, improved in 1 case, ineffective in 8 cases. Thyrotropin adenoma progressed in 1 case.
Analysis by cause of neuronavigation: 9 cases cured, 8 cases in remission, 8 cases progressed, 10 cases invalid and 1 case automatically discharged in the recurrent group; 20 cases of recurrent sex hormone-secreting pituitary adenoma, including 12 cases of GH adenoma, 1 case of PRL adenoma and 7 cases of ACTH adenoma, 6 cases cured (all were ACTH microadenoma), 4 cases progressed and 10 cases invalid. In the invasive group, 2 cases were cured, 22 cases were in remission, 15 cases progressed, and 6 cases were ineffective. 30 cases of invasive hormone-secreting pituitary adenomas (including 7 cases of recurrence), including 21 cases of GH adenoma, 7 cases of PRL adenoma, 1 case each of ACTH and TSH adenoma, 18 cases progressed and 12 cases were ineffective. In the microadenoma group, 45 cases were hormone-secreting adenomas, including 39 cases of ACTH adenoma, 5 cases of GH adenoma and 1 case of PRL adenoma. 38 cases (84.4%) were cured, 1 case was improved and 6 cases were invalid. The group with abnormal thickening of the skull base was cured in 1 case and improved in 2 cases. In the group of pterygoid sinus dysphonia, 1 case was cured, 1 case was improved and 2 cases were invalid. All 4 cases in the carotid artery stenosis group were cured. One case of nasal septal deviation was cured.
Discussion
Neuronavigation is an increasingly widely used three-dimensional guidance technique. In transsphenoidal pituitary adenoma resection, the bony structures such as the pear bone, the ventral wall of the pterygoid sinus, the saddle base, the saddle nodes, and the slope are fixed in position, and there is relatively little displacement of the internal carotid artery in the cavernous sinus segment, so it is well suited for the neuronavigation technique. A number of transsphenoidal pituitary adenoma resections under neuronavigation have been reported in the literature.
In principle, all pituitary adenoma transsphenoidal surgery can be performed with neuronavigation, but because of the high cost of neuronavigators and the relatively high charges for their use, we believe that transsphenoidal surgery with neuronavigation is suitable for the following conditions from our national perspective: recurrent pituitary adenoma after previous transsphenoidal surgery, invasive pituitary adenoma, microadenoma located in the extreme lateral or deep pituitary, poor pneumatization of the pterygoid sinus, abnormal skull base thickening, bilateral internal carotid artery spacing stenosis, and nasal septal deviation.
Most cases of first-time transsphenoidal pituitary adenomectomy can be performed relatively easily under the operating microscope without serious complications. However, for reoperation in cases of recurrence or continued growth of residual tumor after transsphenoidal pituitary adenoma resection, it is relatively difficult to judge the midline structures in the pterygoid sinus because the anatomical structure of the saddle base has been destroyed, and if there is a misdirection in the approach, serious or even fatal complications such as nerve injury and internal carotid artery injury may occur. Neuronavigation, on the other hand, allows the surgeon to correctly identify and maintain the direction of the surgical approach to avoid damage to the nerve or large vessels. Our data also show that for recurrent ACTH microadenomas, a satisfactory biological cure rate can still be obtained with reoperative transsphenoidal surgery under neuronavigation, whereas for recurrent GH and PRL adenomas, although the tumor can be removed relatively satisfactorily under neuronavigation, it is still difficult to obtain a biological cure. In recurrent pituitary adenomas, due to the large number of scar in the operation field, in many cases, the tumor and scar tissue are mixed with each other, which may bring great difficulties to the resection of the tumor. Therefore, for neuroguided transsphenoidal surgery of recurrent pituitary adenoma, the principle of moderation should be adhered to, and the tumor must be removed on the basis of avoiding damage to nerves and blood vessels, because the residual tumor can be treated with postoperative radiotherapy and/or drugs, while the neurovascular damage may be irreversible or even fatal.
In transsphenoidal surgery for microadenomas located in the extreme lateral or deep pituitary, the use of neuronavigation can correctly determine the extent of saddle base exposure and precisely determine the site of microadenoma, thus minimizing the extent of saddle base dura and normal pituitary tissue incision, and better protecting normal pituitary tissue during tumor resection to avoid postoperative hypopituitary function. In our group of 45 cases of pituitary microadenoma, all of them were accurately positioned under neuronavigation, and 38 cases (84.4%) were completely resected and achieved biological cure.
Since the X-ray surveillance screen can only visualize bony structures, it is difficult to determine the location of soft tissues such as tumors, nerves and blood vessels. The nerve navigation can determine the location of the surgical instruments and the location of important nerves and blood vessels, especially the internal carotid artery, relatively accurately, so that the operator can avoid damage to the nerves and blood vessels. Therefore, for trans-pituitary surgery of invasive or giant pituitary adenomas, neuronavigation can be of great help. Of course, with the removal of residual tumor and the descent of the saddle diaphragm, if intraoperative cerebrospinal fluid leakage occurs again, and sometimes there may be intraoperative image drift and positioning errors of navigation because of the subtle displacement of the navigation stent and the positioning ball, therefore, it is inaccurate to judge the extent of resection of invasive or giant pituitary adenoma under neuronavigation. The literature reports that the extent of tumor resection can be judged relatively more accurately with the aid of neuroendoscopy or iMRI, which is conducive to more complete resection of tumors and avoidance of large vessel injury. In our group, the extent of tumor resection was increased by intraoperative neuroendoscopic assistance in 11 cases. In the case of using neurological navigation, it is still necessary to be familiar with the various anatomical landmarks of the transsphenoidal approach and not to trust and rely on the navigation, and intraoperative X-ray monitoring is still the most frequently used method to rapidly determine the direction of the approach in transsphenoidal surgery. In our group, there were five cases in which the direction shown by the navigation probe was found to be inconsistent with the direction and position judged from the anatomical landmarks. After switching to a three-peg head mount and installing the navigation bracket, no further errors in navigation positioning occurred.
Our experience also shows that for invasive hormone-secreting pituitary adenomas, such as GH, PRL, ACTH, and TSH adenomas, although intraoperative neuronavigation can significantly increase the extent of tumor resection, the biological cure remission rate is still relatively low, and excessive pursuit of complete resection can easily cause nerve and vascular damage, which may lead to disability or death. In our group of 30 cases of invasive hormone-secreting pituitary adenomas, although the degree of tumor resection was improved with neuronavigation, none of them achieved biologically curative remission by surgery alone.
In patients with poor pneumatization of the pterygoid sinus, or thickened bone at the base of the skull such as in combination with cranial fibrous dysplasia syndrome, transsphenoidal surgery often requires a long time to grind away the bone and constantly identify and maintain the correct orientation of the surgical approach. This can be achieved relatively simply and easily by intraoperative navigation, which avoids repeated C-arm X-ray monitoring, saving time and avoiding repeated X-ray radiation exposure to the operator. In our group, four cases of malpneumatization of the pterygoid sinus and three cases of abnormal thickening of the skull base were successfully milled through bony tunnels under the guidance of neuronavigation to accurately reach the saddle base.
For pituitary adenomas with bilateral internal carotid artery spacing stenosis, in the past, transsphenoidal surgery was often abandoned in favor of open surgery, which increased the surgical trauma. In such cases, it is relatively easy to perform transsphenoidal resection with neuronavigation, which reduces the surgical trauma. In our group of four cases of pituitary adenoma with bilateral carotid artery spacing stenosis, all of them successfully completed transsphenoidal surgery for total resection of the tumor through neuronavigation and achieved good surgical results of biological cure.
In conclusion, neuronavigation allows transsphenoidal pituitary adenoma resection: (1) easier access to the nasal cavity, butterfly sinus, saddle base and discovery of already defective midline structures; (2) safer and minimally invasive, both for the protection of important neurovascular structures around the saddle area and for the protection of normal pituitary tissues, while also enhancing the operator’s confidence; (3) allows the operator and the personnel involved in the procedure to avoid exposure to X-ray caused by radiation damage; (4) it also expands the indications for transsphenoidal pituitary adenoma surgery to a certain extent.