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Endoscopic Pituitary Surgery: An in vivo model for transnasal transsphenoidal hypophysectomy
By Jarrahy, Reza, M.D., Suh, Richard, M.D, Berci, George, M.D.

Abstract

The transseptal transsphenoidal approach to surgical intervention of the pituitary gland has been described for decades. Its gradual acceptance as the standard of therapy is indicative of general trends toward less invasive means of managing intracranial surgical disease. The evolution of the technique has coincided with advances in medical technology, including the introductions of intra-operative fluoroscopy and operative microscopy. Current progress in the field of endoscopy promises to further this evolution: endoscopic telescopes and instruments have improved upon the optical and technical limitations of the microscope, and require an even less invasive approach to the sella. To test the benefits and limitations of the endoscope in performing transnasal transsphenoidal hypophysectomy in an in vivo model, we operated on two live anesthetized pigs using 4.0-mm zero- and thirty-degree 18-cm long endoscopes. The long lengths of the pig snouts precluded a transnasal approach to the sella; we were, however, able to use the endoscopes to explore the sphenoid sinus, sella turcica, and parasellar regions via a transoral exposure. Digital images of the relevant skull base anatomy were captured. The benefits and limitations of the technique were noted and compared to our experience with microscopy in transsphenoidal hypophysectomy in humans.

Introduction

The evolution of pituitary surgery over the past century dates back to the work of Oscar Hirsch and Harvey Cushing in the early 1900s. Hirsch's dedication to the transsphenoidal technique as the most effective method to approach the sella ran contrary to his contemporary's opinion.13 Cushing, with large series' of cases using both transcranial and transsphenoidal approaches to the sella, would ultimately choose the former as the more efficacious procedure. Citing its distinct advantage in providing a direct and gross exposure of the gland, Cushing helped establish widespread employment of the transcranial method throughout Europe by the 1930s.27

The debate over invasiveness and exposure was sustained by Cushing's assistant Norman Dott. Dott took his experience with both procedures back to the University of Edinburgh. There, while developing several instruments designed specifically for the transsphenoidal procedure, he wrote and lectured in favor of this method and inspired others to use it.2,27 Among those who modeled their practice after him was Gerard Guiot, who credited his revival of the transsphenoidal hypophysectomy in France during the 1950s to Dott's influence.6 Guiot's adaptation of the procedure is especially noteworthy in its correlation with the introduction of intra-operative radiofluoroscopic imaging.27 Likewise, Jules Hardy's praise and emulation of the work of Guiot and Dott is distinguished for his description of the use of the operating microscope, pictures of which he first presented in 1967.7-10 The introduction of microscopy to pituitary surgery ended the discussion on how to maximally expose the gland with the least morbidity – until recently. New advances in medical technology are again at the center of the debate.

Groundbreaking experience with the use of endoscopy, especially in the field of sinus surgery,20-22,24,30,32 has prompted surgeons to explore the benefits and limitations of using endoscopic techniques intracranially. Over the past several years, a handful of authors have reported their experiences with endoscopic telescopes in pituitary surgery as either assistive devices in microscopic procedures or as exclusive means to performing pituitary surgery using varying degrees of intranasal dissection.1,4,11,12,14-19,25,26,28,29,31,33 However, transnasal transsphenoidal resection of pituitary tumors using endoscopy exclusively, without any intranasal dissection other than of the mucosa overlying the sphenoid sinus, is far from common practice: only three centers have presented their experiences with this technique.1,11,16 Originally described by Jho,19 it represents the most direct, least invasive, and most effective means of performing truly minimally invasive pituitary surgery.

In our practice, we have used endoscopy as an adjunct to microscopy in transseptal transsphenoidal hypophysectomy in over fifty cases (unpublished data) and have begun clinical trials with the endoscope as the sole imaging modality. Our observations mirror those that have been previously published. We feel that the dynamic optical capabilities of the endoscope are superior to those of the microscope. Endoscopy reveals residual tumor in the parasellar spaces and defines the important relationships between the pituitary and the surrounding structures more clearly than does microscopy. Further, the endoscopic approach obviates the need for the soft tissue and bony dissection inherent to the transseptal method.

As a prerequisite to widespread adaptation of new endoscopic techniques to transnasal transsphenoidal pituitary surgery intimate knowledge of the anatomy and the technical and practical aspects of the involved instruments is vital. Pursuant to this, we attempted transnasal transseptal hypophysectomy on two live anesthetized pigs entirely endoscopically with the goal of defining a reproducible educational model for this procedure. The use of various endoscopic telescopes in an in vivo animal model was evaluated. The relative advantages and limitations of the technique were compared to our experience in navigating this anatomy in humans under microscopic visualization.

Method

The following procedures were performed on two live 30-kg farm bred swine at the animal research facility of Cedars-Sinai Medical Center in Los Angeles, California. Operative goals and methods were planned in consultation with attending veterinary staff prior to surgery. Our protocol was reviewed and approved by the Cedars-Sinai I.A.C.U.C. board prior to experimentation.

The subject was brought to the operating room and sedated using the following intramuscular agents: ketamine (20 mg/kg), acepropamine (0.5 mg/kg), and atropine (0.05 mg/kg). An intravenous catheter was placed in a large superficial vein of the auricle through which intravenous fluids and thiopental 2.5% (approximately 6-8 cc) was administered. The pig was then intubated and an inhalational anesthetic agent (isofluorane 1-2%) was titrated according to vital signs to maintain anesthesia throughout the surgery. The pig was placed in supine position and prepped and draped in the standard surgical fashion.

Storz™ 4.0-mm zero-degree 18-cm long endoscopic telescopes were passed through one nostril along the ventral nasal concha with the goal of visualizing the endoturbinates of the porcine ethmoid bone and, further posteriorly, the anterior wall of the sphenoid sinus. However, the snouts of the subjects were prohibitively long: the telescopes could not be advanced far enough to visualize the sphenoid sinus. The endoscopes were therefore removed and exposure of the sella was achieved via a transpalatal approach.

The oral cavity was manually opened and held in place with an oral retractor. Under direct visualization, the mucosa of the palate was removed. Next, using a hand-held cutting drill, the posterior palatine and pterygoid bones were dissected, exposing first the vomer and then the sphenoid sinus and its septum. From this point on the dissection was continued endoscopically, with placement of the zero-degree endoscope into the cavity of the sphenoid sinus. The floor of the sella turcica was visualized and removed using microsurgical dissecting instruments. The exposed dura was removed to reveal the underlying pituitary gland. Further exploration of the sella and parasellar spaces using the thirty-degree endoscope allowed a detailed examination of the pituitary gland, hypophyseal stalk, cavernous sinuses, and carotid prominences. Following this exploration, a partial hypophysectomy was performed.

At the completion of each procedure, the animal was euthanized by the assistant veterinary staff with a high-concentration parenteral dose of potassium chloride.

Results

As mentioned above, the length of the pig snout precluded transnasal access to the sphenoid sinus and sella, as was our original intention. Modification of our surgical plan based upon the porcine cranial anatomy allowed us to expose the sphenoid sinus via a direct intraoral, transpalatal, technique that exposed the sphenoid sinus and sella turcica extremely well.

Within the sinus, the 4.0-mm zero-degree endoscope provided an excellent image of the surgical field. The ability to rotate and turn the endoscope was particularly useful in surveying the anatomy of the sphenoid sinus. The sinus was large enough to accommodate the endoscope and the dissecting instruments that were passed alongside it.

Technical difficulties in maneuvering the endoscope and instruments were experienced during the dissection of the floor of the sella: with one hand holding the endoscope, the surgeon had only one hand free to manipulate the surgical instruments. An additional technical challenge was encountered in the pollution of the endoscope with blood and other secretions from the surgical site. The scope was repeatedly removed from the surgical site after contact with fluid and debris to be cleaned. Repetitively repositioning the scope into such a confined space was a painstaking task. (We are currently researching and developing holding arm systems that will stabilize the endoscope and allow the surgeon to operate with both hands. As well, we are testing various models of endoscope-fitted lens irrigataion systems that will allow continuous rinsing of the endoscope in situ.)

Within the sella, the zero-degree scope continued to provide excellent visualization. Despite its maneuverability, however, our view of the surrounding regions remained sub-optimal. When we removed the zero-degree endoscope and placed the thirty-degree scope into the sella, the change in imaging was remarkable. The thirty-degree angle of the lens enabled us to overcome the obstacles presented by the bony anatomy of the sella. We were able to look into the supra- and parasellar spaces and see the hypophyseal stalk, cavernous sinuses, and pulsations of the carotid arteries with a definition unparalleled in our microscopic experience.

Removal of the pituitary was ultimately undertaken with great appreciation of the relationships between the gland and proximal structures.

Discussion

Medical technique and medical technology have evolved hand in hand over the centuries, but it has not always been clear which has preceded the other. Do new instruments and inventions make new methods possible, or do new procedures provide the impetus for the creation of special devices suited to those procedures? Often progress in instrumentation and application is coincident.

Regarding surgical approaches to the pituitary gland, innovation in radiographic and optical instruments helped to end a half-century of debate. When he declared the superiority of the transcranial method for resecting pituitary tumors, Cushing did not have the benefit of intra-operative fluoroscopy or microscopy. Without the tools needed to allow a less morbid procedure, he argued that removal of the calvarium was the only way to adequately expose the gland. The potential risks associated with craniotomy outweighed the benefits of the more thorough resection he felt he could achieve.27

New questions in the field of pituitary surgery have arisen, indicative of the rapid evolution of medical technology. Do we now possess new technologies that will allow us to approach the pituitary gland in an even less invasive fashion than with the operative microscope, and do these innovations truly represent improvement over the current standard practice? The technologies in question are vested in the dynamic field of endoscopy, adaptation of which has been undertaken by all surgical specialists to suit their operative needs. Pituitary surgeons have expanded upon the work of otolaryngologists who have described various intranasal approaches to the sphenoid sinus using endoscopes.4,12,14,26,28,33

The benefits of an endoscopic method of transnasal transsphenoidal hypophysectomy are multifold. First, the more flexible maneuverability and superior panoramic perspectives offered by endoscopy heighten the surgeon's awareness of the vital structures that reside in and around the sella. These structures account for a host of potentially irreversible complications in pituitary surgery. Endoscopy may ultimately prove to offer such a superior exposure that tumor can be resected more completely, reducing rates of recurrence as well as the need for secondary operation or adjunctive therapy. Helal12 reports endoscopic discovery of residual tumor in 40% of patients after resection by standard microsurgical technique was determined to be complete. Second, by obviating the need for intraoral and nasal dissections, the morbidities associated with these extra procedures are eliminated. Third, due to the less invasive nature of the procedure and the lack of need for postoperative nasal packing, the patient experiences less discomfort and should be able to be discharged from the hospital more rapidly.

Our study was conceived to demonstrate two principles. The first is that access to and adequate exposure of the sphenoid sinus can be achieved completely transnasally. Second, we hoped to document our claim that sellar, suprasellar, and parasellar structures are better visualized and therefore more accessible with the endoscope. In particular, we hoped to use the optical properties of the endoscope to visualize those structures that we are most concerned about in pituitary surgery (the cavernous sinuses, the carotid arteries, and the optic chiasm), that are not directly exposed under the microscope. We hoped to accomplish these things in an animal model that could be applied toward educational and training efforts.

As to the latter goal, we were able to compare our observations in this animal model to our own result in human patients, as well as to the reported results of others. Compared to the operating microscope, the endoscopes yield images of the sphenoid and the sella of superior clarity, providing a panorama of the surgical field not otherwise attainable. Scopes of varying optical configurations broaden this perspective. Once in the sella, replacement of the zero-degree with the thirty-degree endoscope offered a remarkable improvement in the breadth of exposure. The thirty-degree scope allowed us to overcome the anatomical boundaries set by the bony sella and look around corners to see the hypophyseal stalk, the detailed trabeculations of the cavernous sinus, and the pulsations of the carotid arteries. The parasellar spaces were immediately accessible in this new surgical field; the implications for more thorough resection of pituitary tumor were abundantly clear. These subjective observations are not only consistent with the results of others who have employed endoscopy in this region, but also support the objective data presented by Helal.12

Regarding the goal of describing a reliably reproducible animal model for the transnasal approach to the sphenoid sinus and sella, we were less successful. The snout of the standard farm bred swine was too long to allow visualization of the most posterior aspect of the nasal cavities, and therefore the sphenoid ostia, with the endoscopes we were using. Thus, the swine proves not to be an optimal system for the practice of this approach. This is unfortunate, as the intranasal part of the overall technique is especially challenging in human patients due to the spatial constraints of narrow nasal passages, the relative awkwardness of manipulating long instruments within such a space, and the obscuring effects of blood and secretions that emanate from mucosal surfaces that have been manipulated.

Nevertheless, this observation should not detract from the value of this model in the reproduction of the intracranial techniques used in endoscopic pituitary surgery. Without an animal model from which to draw, practitioners of this procedure have a vast body of literature, primarily based in the field of otolaryngology, which describes the endoscopic surgical anatomy of the nasal cavities and paranasal sinuses. 4,5,11,12,14,18,20-22,24,25,28-30,32,33 However, descriptions of the endoscopic surgical anatomy of the sella turcica and parasellar spaces is relatively sparse. Moreover, it is within this area, where the margin for error defined by surrounding critical structures is so small, that familiarity is critical to success. We echo the statements of Jho (and others) regarding the challenges to successful outcomes: "Certainly, a learning curve exists for a surgeon who is not familiar with the endoscope. Its use requires different surgical skill from those necessary in microsurgical techniques... A surgeon inexperienced with this technique may become frustrated if the two instruments consistently strike each other in the small operating space. Practice will overcome this problem."16

Endoscopic pituitary surgery in its most evolved form – that which limits the amount of intranasal surgery only to dissection of the mucosa overlying the sphenoid ostium – is still relatively rare. The collective work of Jho16, Cappabianca1, and Heilman11 represents experience with only 65 patients in which this technique was successfully employed, the bulk of whom (46) were treated at only one of these centers. Nor is the body of work that precedes the work of Jho quite extensive: Gamea et al4, Helal12, and Yaniv33 have presented their individual experiences with combined endoscopic and microsurgical techniques in a collective total of 51 patients. Jankowski et al14, Sethi28, and Rodziewicz et al26, all of whom have employed an endoscopic approach to the pituitary gland with varying degrees of intranasal turbinate and septal dissection, present 53 patients in total.

All of the published results offered thus far are summarily encouraging, and collectively signal the potential for univversal change in the performance of pituitary surgery. More objective data, such as that presented by Helal12, will further support this movement. Popularization, however, of a truly minimally invasive approach to pituitary surgery hinges on the development of adequate educational and training resources geared toward familiarizing surgeons with this new frontier.

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