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Recent Developments in Endoscopic Endonasal Approach for Pituitary Adenomas
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.287671
Keywords: Inventions, neuroendoscopy, pituitary neoplasms, surgical oncology technologyKey Message: Significant surgical and technological advancements have happened for endoscopic transsphenoidal pituitary surgeries. These have led to higher resection rates, better patient outcomes, and improved surgical simulation and training. A higher cost remains a concern.
The endoscopic transsphenoidal approach has become a standard for pituitary adenomas (PA).[1],[2],[3] The approach has several advantages of minimal invasiveness, good vision, panoramic view, magnification, and the ability to perform extended approaches.[4],[5] However, these also have their limitations. For instance, a lack of depth perception, a long learning curve, potential damage to the nasal structures, difficulty in performing hemostasis, and CSF leaks. This review highlights newer advances in the field of endoscopic pituitary surgery. The utilities, advantages, and limitations are mentioned.
A thorough English literature search of the last ten years on PubMed and Google Scholar with the keywords – “Pituitary AND Neuroendoscopy” was done. A total of 345 articles were found (44 review, 193 original), of which relevant articles were chosen. Along with these, the senior author's (PSC) experience was also incorporated. Intraoperative MRI (IMRI) Both low-field (0.15 – 0.3 T) and high-field (1.5 – 3T) IMRI have shown an increased extent of resection in pituitary macroadenomas.[6],[7],[8] Zaidi et al. showed an increase in gross total resection, from 60% to 80% in 27 PA patients.[9] For the invasive PA (Knosp grade III and IV), Hlaváč et al. compared the intraoperative and postoperative resection volume in 45 patients and found 46.7% additional resection using the IMRI (P < 0.001).[10] Similar results were seen in other studies.[11],[12] Literature suggests that with the endoscopic approach, the need for IMRI may be significantly higher in invasive PA compared to the non-invasive ones.[13] IMRI may also help to identify the normal PA during surgery. Schwartz et al. showed that the endoscopic resection and IMRI are complementary to each other, wherein they found the presence of both true positive and false positive residuals (confirmed with endoscopy) during the surgery.[14] IMRI can also complement the navigation by acquiring the intraoperative data. The advantage of IMRI for visual improvement, after the surgery, is not so robust, since most of the decompression happens before the IMRI scan.[10] The authors have the experience of 1.5 Tesla IMRI with a rotating table. This system avoids the need for shifting of the patient from the operating table to the MRI table. The surgical field comes outside the 5 Gauss line. The other way of using an IMRI is to place the MRI in a separate room of the operating theatre, which can be used for multiple surgeries. This makes the IMRI cost-effective. Limitations of IMRI include the added cost and increased duration of surgery. Artifacts due to nasal packing may look as tumor remnants, and one needs the experience to interpret them accurately. From a cost-effective perspective, it is important to have an IMRI also to be capable of diagnostic patient use so that the same may be performed when surgeries are not going on. Neuronavigation Neuronavigation has become vital equipment in the operating room in the last two decades.[15],[16] Studies have shown an increase in efficacy of the endonasal endoscopic surgery with the neuronavigation.[17] The navigation is especially useful in conditions with distorted anatomy and recurrent cases.[18],[19] It increases the surgeon's ease and accuracy and decreases the operative time.[19] Recently, an “Autostereoscopic 3D neuronavigation” has come, which combines the 2D images of axial, sagittal, and coronal planes, into one integrated 3D image, and gives a better spatial view.[20] The technique also allows reverting to the traditional 2D neuronavigation, whenever required. Relaying marginally offset images to each eye develops the 3D stereoscopic images. The offset images can be projected using parallax barriers or multiple projectors.[21],[22] Another advantage of the “Autostereoscopic 3D neuronavigation” is the avoidance of cumbersome stereoscopic glasses. In a series of 10 patients of PA done using 3D Neuronavigation, Amr et al. found the technique to be safe and effective.[20] It provided the surgeon with a better orientation – especially in distorted anatomy during recurrent cases, both preoperatively and intraoperatively. Another advent in navigation is the “Multimodal navigation” that utilizes the IMRI and vascular Doppler. Dolati et al. showed the safety and accuracy of this technique in 25 PA cases and described it to be useful for complicated cases and less-experienced surgeons.[23] The neuronavigation becomes unreliable after the CSF leak that may cause a brain shift. The equipment also increases the cost significantly. A CT scan of thin cuts increases the radiation exposure preoperatively, but since it avoids the need for intraoperative fluoroscopy, the overall radiation may be equal. The navigation equipment also requires space in the operating room, which also needs to be considered. In pituitary endoscopic surgery, neuronavigation is mostly of use to gain access to the sphenoid and sellar region. Endoscopic augmented reality navigation system “Augmented reality” is a technology through which a computer-processed image is projected over the patient in real-time. This leads to a combination of virtual images and reality. The technique consists of virtual image creation using preoperative imaging, image projection of the computer-generated image, and manual registration using fiducials. Specialized equipment are needed for this system, including camera, projectors, fiducials, and displays.[24],[25] The displays are either optic or head-mounted. Besharati et al. compared the augmented reality system with conventional neuronavigation in 5 patients of brain tumor, and found an insignificant error in the accuracy (projection error 1.2 ± 0.54 mm).[25] The system is especially helpful for displaying major structures viz. nerves and vessels, thus reducing the errors and increasing safety and reducing the operative duration. A hands-free control using voice recognition functions may also be used. The device can also be used for simulation and education.[26] The AR system is especially useful for brain and skull tumors because of their negligible movement during the surgery.[27] EASYTRAC ® retractor The conventional endoscopic endonasal binostril approach entails the creation of a nasal mucosal flap, resection of the posterior nasal septum, and sometimes excision of the middle turbinate. This may cause significant nasal morbidity to the patient.[28] Also, the approach needs good anatomical knowledge of nose and may require the need of ENT surgeons in the initial part of the learning curve. The transseptal midline approach has been used in the past.[29],[30] It is an easy approach but has the limitation of providing a narrow corridor. With this technique, the surgeon requires a rigid retractor, like Hardy's retractor, which may have its own complications. The senior author (PSC) has devised a deployable dynamic retractor system that is soft, malleable, effective, easy-to-use, preserves the nasal septum, and associated with minimal nasal morbidity (patent number - R20191028780). The preliminary work has been published earlier.[31] The retractor is available in 3 sizes – pediatric (10 mm × 100 mm), small (15 mm × 150 mm), and large adult (20 mm × 150 mm), as shown in [Figure 1]. The retractor is a 'V' shaped construct, held folded with a wire and ring. During the surgery, a linear incision is made in the anterior part of the nasal septum, and mucosa is stripped off. The EASYTRAC® retractor is inserted in the submucosal tunnel and deployed by pulling the ring and removal of the wire. This makes the retractor assume its shape. Thereafter, the retractor is used dynamically using the suction and working instruments. After the tumor resection, the retractor is simply pulled out, the nasal septum is pushed back in the midline, and the mucosa stitched back to the septum. The nasal cavity remains pristine in the end.
The EASYTRAC® retractor is excellent for sellar and sellar-suprasellar lesions. The tumors extending significantly in parasellar compartments are a relative contraindication. However, even these can be managed after gaining sufficient experience. Diffusion Tensor Imaging (DTI) for visual tracts Visual impairment is one of the commonest symptoms caused due to PA and is potentially reversible.[32] The conventional MRI can detect the relation of the tumor with the visual pathways, but not the physiological disruption of them. Although, one can predict the degree of visual impairment with the amount of chiasmal lift,[33] it is challenging to visualize at-times and has to be measured from the internal surface landmarks making it subjective. Furthermore, the clinical ophthalmological examination is often subjective. The DTI is an MRI technique based on the fractional anisotropy (FA) of the white fibers. Lilja et al., evaluated 23 patients of PA and 20 healthy controls and found a significant correlation of the radial diffusivity and degree of visual field defect (r = -0.58, P < 0.05).[34] The axial diffusivity, if decreased in patients, signifies irreversible visual deficit.[34] The DTI has the advantage of non-invasively identifying the visual deficit, and predict its recovery. Secondly, the required software generally comes with most of the MRI machines. Extended approaches to the cavernous sinus Tumors extending to cavernous sinuses are challenging in terms of their resection and decompression of the cranial nerves. The extended approaches help to tackle these tumors safely and effectively.[4],[5],[35],[36] The initial steps remain the same as for the standard endonasal transsphenoidal resection of PA. The patient is placed in the supine position with the head rotated, about 15 degrees to the right side, i.e., towards the surgeon. The binostril approach is advocated for extended approaches. Initially, the 0 degrees, 18 cm long, 4 mm wide endoscope is utilized, and later for the rostral, caudal, or lateral extents, the angled endoscopes with 30°, 45°, or 70° are used. The middle turbinate is removed on the right side and lateralized on the left side. The mucosal flap is lifted from the septum (generally from the right side), sparing 1 cm superiorly for olfaction, and kept in the choana securely. The posterior 1/3rd of the septum and anterior wall of sphenoid sinus, until medial pterygoid plates, are removed to create a wide rectangular working space. Thereafter, one can see the medial and lateral opticocarotid recesses [Figure 2]. Tumors extending significantly in the suprasellar region and anterior cranial fossa need drilling of the tuberculum sellae and the planum sphenoidale [Figure 3]. Tumors extending into the cavernous sinus need eggshell drilling and removal of the bone over the ICAs. Thereafter, angled instruments can be used to resect out the tumors. Taniguchi et al. observed 56% gross total resection of the Knosp grade 3 and 4 PAs through the endoscopic transsphenoidal transsellar route.[37] Alternatively, for the lateral cavernous sinus tumors, some authors have proposed a transethmoidal approach to the cavernous sinus that runs lateral to the middle turbinate.[36]
Optical fluorescence agents Recently, three optical fluorescence agents have been tried for PAs. These include Indocyanine green (ICG) angiography, Sodium fluorescein dye, and 5-aminolevulinic acid. For the endoscopic transsphenoidal surgeries, the ICG angiography has the strongest prospect and evidence amongst these.[38] The special equipment required for the endoscopic indocyanine green (eICG) angiography are a light source (capable of emitting white light and infrared light separately) and an ICG filter for the infrared light that can be introduced in front of the lens whenever required. Excitation and observation are done at about 800 nm wavelength. The eICG angiography can help to note the real-time position and patency of the vessels. The dye is preferentially taken up by the normal pituitary gland and tumor-invaded dura, and thus the tumor can be differentiated from them that enhances in the later phase.[39],[40] It is especially helpful in visualizing the ICA, both before the sellar drilling, and during the cavernous sinus exploration for an invasive PA. The ICG dye may lead to an increase in the resection rates and better preservation of the endocrine functions, than the surgery without it.[41] The dose of ICG is 0.2-0.5 mg/kg of body weight administered intravenously. The enhancement of the ICA is visible after 15-20 seconds of injection of the ICG dye, and it is about 10 times longer compared to the microscopic ICG angiography.[42] The dye is quite safe, but as a precautionary measure, one should do a sensitivity testing before giving the actual dose of the drug. There are some limitations like the visualization of ICA with bone over it is not satisfactory, compared to when it is naked. Furthermore, simultaneous visualization of the ICG angiography and real-time imaging is presently not possible. Robotic surgery Robots can be of considerable help in neurosurgery.[43],[44],[45] The senior author (PSC) has utilized robotic assistance (ROSA, Medtech, Montpellier, France) in more than 100 pituitary surgeries (ROSA, Stryker). The robot acts as a stable holder with haptic feedback during the movement of the scope. However, the main disadvantages of this kind of utilization of Robotic assistance are related to the bulky nature of the current systems, slower movements, and also occasional 'freezing' which may happen. Other uses of robots can be in robotic telesurgery. Wirz et al. operated two phantom pituitary tumors (one locally and one 800 km away) and found latency of <100 msec, without any significant difficulty.[46] With the benefit of robotic telesurgery, experienced pituitary surgeons can potentially help many patients living in remote areas. However, currently, such technology is still not available for routine clinical use. Even for the local situation, slender instruments with the added degrees of freedom of movements of a robotic arm can be utilized.[47] 3D endoscopic system The major disadvantage of the endoscopes, compared to the microscopes, has been the lack of stereopsis. This limitation can be overcome by the use of 3D endoscopes that provides depth perception. Apart from the addition of different scopes, monitor, and polarizing glasses, the surgical setup remains the same. Bickerton et al. found the 3D endoscopic system to decrease operative errors and operative duration in an experimental design, especially during the initial part of the learning curve.[48] The view of the 3D standard definition scopes was earlier inferior to the 2D scopes in terms of brightness,[49] however, with the advent of 3D high definition (HD) scopes, the view has become improved and is non-inferior to the 2D scopes.[49],[50] Inoue et al. observed an excellent spatial orientation of the sellar, internal carotid artery, optic prominence, cribriform plate, optic chiasma, and surrounding blood vessels in their series with the 3D HD system.[50] One limitation of the 3D system is the need for polarizing glasses to be worn by the surgeon, which may be vertiginous and uncomfortable to some. However, with practice, the surgeon habituates and becomes comfortable. 4K And 8K ultra-high-definition endoscopes Current HD endoscopes have an image resolution of 1920 × 1080 pixels. 4K ultra-HD provides a four-fold increased image resolution than the 2K ones. D'alessandris et al. compared their series of endoscopic pituitary surgeries using HD endoscopes with 4K endoscopes and found the latter to have higher reliability in the extent of resection, and significantly reducing the residuals, particularly in the recurrent cases.[51] The 8K ultra-high-definition endoscopes have a 16 times higher resolution than the HD endoscopes with a resolution of 7680 × 4320 pixels. Though these have not been used for the pituitary surgeries until now, their use in general surgery has shown a considerably better viewing experience than their previous ones,[52] and they are possibly the future. 3D printing model of pituitary macroadenomas Building a “3D model” requires the CT and MRI data to be acquired, segmented, making of a virtual model, conversion to a stereolithography file format, and printed. The acquisition of the CT and MRI data is made in thin slices, – 0.625 mm, and 1 mm, respectively. The segmentation is done either automatically or manually, depending upon the desired structures like nasal septum, sphenoid septum, internal carotid artery, sella, clivus, etc. Data can be converted into the 3D model using software like MIMICS (Materialise, Leuven, Belgium), and thereafter into a stereolithography file format (*.stl). Finally, the file can be taken out with a 3D printer. The material used for printing is acrylate resin with a thickness of 0.245 mm. Huang et al. compared ten patients of pituitary macroadenoma operated with 3D printing with an equal number of patients operated without 3D printing and found significantly less blood loss and operative time in the 3D printing group.[53] The complications were also half in the 3D printing group. The 3D printing technique may be helpful for beginners in the endoscopic endonasal pituitary surgeries. For experienced surgeons, it may be helpful in difficult situations like tumor going in the cavernous sinus, or lateral to carotids. The presurgical evaluation of the model is helpful for a comprehensive evaluation of the structures. It increases the surgeon's satisfaction and avoids surprises.[53] Lastly, the model may also help the clinician to easily explain the location, complexities, and possible complications to the patient and their relatives. Limitations of 3D printing include a significant time for their manufacturing – the designing time takes approximately 2-4.5 hours, and the printing time nearly 10-22 hours. However, since pituitary macroadenoma is generally an elective surgery, the required time for 3D printing can easily be brought out. Secondly, real-life situations, like bleeding, lens fogging, and others, are not replicated. Lastly, the models increase the cost of the procedure. However, since the 3D models may reduce the operative time, the actual procedural costs may be decreased, which may be in the range of 15-20 US$ per minute (in 2010).[54]
Substantial newer advances are happening for endoscopic pituitary surgery. The advantages include fewer residuals, minimal damage to nasal structures, shortening the learning curve, easy and better identification of vessels, increased safety, and shortening the operative duration.[10],[20],[31],[41],[52],[53] Invasion into the cavernous sinus, which was an independent predictor of the decreased extent of resection and increased chances of recurrence, can be tackled using the newer advances.[4],[5],[36],[55] These advents are important for both improving patient outcomes and teaching the younger generation of surgeons. These innovations may increase the financial burden. However, the cost-factor gets negated when the newer technology decreases the operative duration.[54] Secondly, how much of these advents can change the outcomes in the hands of an expert surgeon needs to be seen. Future research will continue to bring new technologies in the field of endoscopic pituitary surgeries. Indeed, these will improve patient outcomes, especially in the early part of the learning curve. A robust randomized controlled trial comparing these with the conventional endoscopic system is currently needed to find their effectiveness for the experienced pituitary surgeons.
The new advancements for endoscopic pituitary surgeries have provided enhanced patient outcomes and decreased intraoperative errors. Their cost remains a significant limitation. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]
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