1    Introduction and Historical Perspective

Harvey Cushing, 19121

Ever since Pierre Marie recognized acromegaly as a pituitary-related syndrome in 1886, intense vigor has characterized the search for knowledge related to the anatomy, physiology, and pathology of the pituitary gland.² Interdisciplinary research and collaboration have allowed a dramatic transformation in the management of pathology of the sellar and parasellar region. Over the past century, collaborative efforts have resulted in medical and surgical advances that allow us to preserve normal function, restore vision, and restore to health a group of patients who were once uniformly condemned to disability and death.

Early Approaches to the Sellar and Parasellar Region

Initial attempts at the surgical management of pituitary lesions were made primarily in patients with large lesions who presented either with the characteristic visual loss associated with compression of the optic chiasm or with symptoms and stigmata of acromegaly. The first published cases of treatment with craniotomy by Sir Victor Horsley and others were not uniformly encouraging.3 Because surgeons were unaware of the intricacies of the hypothalamic-pituitary axis and unable to properly visualize the sella, early procedures were blunt and largely blind attempts to perform what would “generously” be called hypophysectomy. Horsley’s early attempts at subfrontal approaches were plagued by complications secondary to the extent of cerebral retraction necessary to visualize the sella. In 1893, under the encouragement of Horsley, Caton and Paul in Liverpool used a subtemporal approach in a patient with acromegaly⁴ (Fig. 1.1). It would be another 15 years before Schloffer attempted to use a more direct transnasal transsphenoidal route to the sella, which resulted in the patient’s death due to cerebrospinal fluid leak and meningitis.⁵ Not discouraged by this early result, surgeons developed a variety of more successful transsphenoidal approaches nearly simultaneously in the early 1900s. Kanavel and Kocher introduced the sublabial approach, which Cushing popularized while he was at Johns Hopkins^6–8 (Fig. 1.2). Oskar Hirsch, then in Vienna, developed a transnasal transseptal approach, which became the basis for every subsequent endonasal operation for pituitary lesions.⁶

Fig. 1.1 Example of the subtemporal approach originally reported by Caton and Paul, and later refined by Walter Dandy. (Illustration by Max Brödel, 1915. From the personal collection of Dr. Edward R. Laws Jr.)

In 1927, near the end of his tenure at the Peter Bent Brigham Hospital in Boston, Cushing abandoned the transsphenoidal approach for craniotomy for most of these lesions (Fig. 1.3). In 1933, Hirsch relocated to Boston, continuing to use the transnasal transsphenoidal approach long after much of the growing neurosurgical community had followed Cushing’s lead.⁹ Hirsch recognized the limitations of both transsphenoidal and transcranial operations in completely resecting pituitary tumors. With great prescience, in 1910 Hirsch used local irradiation with an endonasal radium bomb under roentgenographic guidance as adjuvant therapy, thus beginning both image guidance and radiosurgery for sellar lesions¹⁰ (Fig. 1.4).

Fig. 1.2 Example of the sublabial transsphenoidal approach popularized by Harvey Cushing. (Illustration by Max Brödel, 1912. From the personal collection of Dr. Edward R. Laws Jr.)

Fig. 1.3 Example of the frontotemporal approach popularized by Harvey Cushing. (Illustration by Max Brödel, 1915. From the personal collection of Dr. Edward R. Laws Jr.)

Fig. 1.4 (A) Hirsch’s original schema for transnasal delivery of radium therapy to the sella. (B) Lateral skull X-ray as used by Oskar Hirsch for image-guided delivery of a radium bomb to the sella. (From Hirsch O. Symptoms and treatment of pituitary tumors. AMA Arch Otolaryngol 1952;55(3):268–306. Roentgenogram from the personal collection of Dr. Edward R. Laws Jr. Reprinted with permission.)

The Birth of Microneurosurgery

As surgeons across the globe struggled to visualize the pituitary from both the transsphenoidal and transcranial routes, a quiet revolution was beginning in Stockholm. In 1921, Carl Nylén, an otolaryngologist at the University Clinic in Stockholm, performed the first microsurgery with a monocular dissecting microscope11 (Fig. 1.5). A year later, Gunnar Holmgren, Nylén’s chief, attached a light source to a binocular microscope. This allowed three-dimensional depth perception, and the external light source made it possible to work at even higher magnification than ambient light would.¹² In 1938, two otolaryngologists, Tullio and Calicetti, working in Parma, Italy, overcame two more limitations; they mounted the microscope on a counter-weighted base to minimize vibrations and mounted a prism beam splitter in the optical pathway, which allowed two surgeons to work with the same field of view. These and other refinements were ultimately incorporated in the first generation of operative microscopes in the early 1950s, when commercial production for use in otolaryngology and ophthalmology began.¹²

Microneurosurgery as we know it was born on August 1, 1957, when Theodore Kurze at the University of Southern California, encouraged by William House’s feats of microscopic middle ear surgery, brought a microscope into the operating room to assist with resection of a facial nerve schwannoma.¹³ One year later, the first interdisciplinary microsurgical laboratory was established by R. M. P. Donaghy in Burlington, VT.¹⁴ Over the next decade, collaboration between neurosurgeons and vascular surgeons, building on the early experience of ophthalmologists and otologists, resulted in new instrumentation and techniques. These were taught to M. Gazi Yaşargil, who returned to Zurich in 1967 after a year in Donaghy’s laboratory to perform the first cerebrovascular bypass.¹⁵

With the newly found ability to illuminate and visualize deep structures, neurosurgeons and otolaryngologists began to approach the sellar and parasellar region with bravado. In the 1950s and 1960s, Smith and Ketcham’s reports of combined transfacial and transcranial approaches to the paranasal sinuses re-ignited interest in radical resection of tumors in this region.¹⁶ Parkinson reported one of the first successful microsurgical approaches to the cavernous carotid.¹⁷ Over the next 20 years, the field of microscopic neurosurgery of the skull base underwent a period of exponential growth and popularity. Aided by the anterior and middle fossa approaches described by innovators such as Dolenc, Sekhar, and Al-Mefty, and the transfacial approaches described by Smith, Ketcham, VanBuren, and others, surgeons were no longer impotent in addressing complex lesions of the sellar and parasellar regions via transcranial and transfacial approaches.^18,19

Fig. 1.5 (A) Carl Nylén and (B) his original operative monocular microscope. (From Kriss TC, Kriss VM. History of the operating microscope: from magnifying glass to microneurosurgery. Neurosurgery 1998;42(4):899–907. Reprinted with permission.)

The Resurgence of Transsphenoidal Surgery

Norman Dott returned to Edinburgh after spending 1923–1924 in Cushing’s clinic and surgical theater at the Brigham. In contrast to most surgeons, who followed Cushing’s lead in abandoning the transsphenoidal approach, Dott continued to practice and refine it over the next 30 years20 and demonstrated its virtues in the mid 1950s to his pupil, Gerard Guiot of France. Guiot was an extraordinary innovator, and he designed new instrumentation, including an endoscope, to facilitate the operation. However, he abandoned the endoscope because of its poor illumination and visualization compared with the operative microscope. Guiot adapted intraoperative fluoroscopy, using air and contrast to localize instruments in the sagittal plane and visualize the extent of tumor resection²¹ (Fig. 1.6). This allowed him and his brilliant pupil, Jules Hardy of Montreal, to safely and accurately work above the sella under indirect visualization. This marked the beginning of real-time image guidance in pituitary surgery, which continues to evolve today.

While working with Guiot, Hardy began to use the operating microscope and microtechnique in pituitary surgery. In another example of simultaneous advancement, Hardy reported the use of the operating microscope for selective hypophysectomy in 1965—the same year Leonard Malis, at Mount Sinai Hospital in New York, used the operating microscope to completely resect a craniopharyngioma in a patient with a prefixed chiasm.^22,23 The advancements in microsurgery introduced by Yasargil and Malis—namely, bipolar electrocautery for hemostasis and microsurgical techniques—were adapted by Hardy for pituitary surgery. Hardy’s demonstration in the late 1960s that one could do selective operations to remove pituitary microadenomas, while preserving the normal pituitary gland, was a revolutionary concept and led to renewed interest in transsphenoidal microsurgery for the treatment of pituitary tumors.^24,25

Radiosurgery of the Pituitary and Surrounding Areas

The development of roentgenography in 1896 and its ability to visualize the bony structures in the region of the sella became not only a key factor in the anatomic diagnosis of pituitary disease but also the basis for the radiosurgical treatment of many pituitary disorders. In 1901, Oppenheim reported the first use of roentgenography to diagnose a pituitary tumor. By 1907, the same year that Schloeffer attempted the first transsphenoidal pituitary operation, physicians were beginning to use X-ray therapy to treat acromegaly. In 1909, Gramegna, in Venice, reported his 2-year experience treating a patient with acromegaly by directing X-rays transorally to the sella.26 That same year, Béclère reported a case in which the enlarged sella of a 16-year-old giant was irradiated with X-rays, and after the patient’s vision improved and headaches abated with irradiation alone, Béclère abandoned his plans for craniotomy.²⁷ External beam radiation therapy was demonstrated to be a viable alternative to surgery when he reported the patient’s 5-year symptom-free follow-up in 1913.

With the Curies’ discovery of polonium and radium as sources of ionizing radiation, surgeons began to experiment with crude forms of brachytherapy. In 1912, Hirsch reported his use as early as 1910 of a radium “bomb” placed transnasally, with image guidance, to treat a pituitary tumor.^6,10 Cushing’s case logs for the decade from 1914 through 1923 reveal several cases in which he used brachytherapy, although he was not enthusiastic about the results.²⁸

Fig. 1.6 Operative setup as originally reported by Gerard Guiot and later refined by Jules Hardy. (From Hardy J. Transsphenoidal hypophysectomy. J Neurosurg 1971;34:582–594. Reprinted with permission.)

The end of World War II also brought several scientific and technologic advances to medicine. The cyclotron, developed by Ernest Lawrence at Berkley National Laboratory, provided not only a sustainable source of fissile material for military purposes but also a new source of high-energy protons and helium ions for use in external beam radiotherapy. Lawrence’s brother John began experimental treatments with the synchrocyclotron in patients in the early 1950s.29 These treatments of neurosurgical disease were expanded upon in the early 1960s by Kjellberg at Massachusetts General in Boston, who treated patients in the Harvard cyclotron.³⁰ (Fig. 1.7).

The end of the war also brought a new exchange of ideas, such as the fateful discussion in 1947 between Sir Hugh Cairns and Lars Leksell at the first meeting of the Scandinavian Neurosurgical Society in Oslo. Encouraged by Cairns, Leksell proceeded to develop a polar-coordinate stereotactic frame for arc-based neurosurgery.³¹ After early experiments, Leksell was dissatisfied with the collateral damage and imprecise therapy delivered by coupling his frame with existing X-ray and proton sources.

The delivery of the first production gamma knife in 1968 to the Karolinska Institute in Stockholm ushered in the era of “radiosurgery,” a term coined by Leksell to suggest the idea of an operation in which the surgeon used a single dose of radiation as precisely as a knife to “excise” (or in this case inactivate) a lesion.^{31 (p 4)} Over the years, stereotactic radiosurgery (gamma knife in the late 1960s, LINAC [linear accelerator] in the early 1980s, CyberKnife in the 1990s) has become an indispensable tool in both the primary and the adjuvant therapy of sellar and parasellar lesions.

Fig. 1.7 Raymond Kjellberg fitting a patient with a stereotactic frame for proton beam therapy at the Harvard Cyclotron ca. 1960. (From Wilson R. A Brief History of the Harvard University Cyclotrons. Harvard University Press; 2004:104–105. Reprinted with permission.)

The Rise of Endoscopic Skull Base Surgery

Although the endoscope was used with varying success as early as 1910 for intraventricular surgery, its resolution (and therefore utility) was limited in both cranial and endonasal surgery until the mid 20th century.32 Two dramatic design advances in the 1950s—the Hopkins rod-lens and Storz “cold” illumination—suddenly allowed surgeons to see with the same clarity as did an operative microscope.³³ As the resolution and illumination of endoscopes improved, they were rapidly adopted by rhinologists for use in sinus surgery. A whole armamentarium of instruments and techniques was developed and refined by otorhinolaryngologists working in relative isolation from neurosurgeons until the mid 1990s, when, as with microsurgery in the 1950s, collaboration between the two disciplines launched a new era in surgical technique.

In the late 1970s, the first reports of endoscopically assisted transsphenoidal surgery emerged.^34,35 Over the ensuing years, improvements in lighting and digital cameras allowed the development of endoscopes with visualization besting that of a galilean instrument. Angled lenses allowed surgeons to look off axis, and combined with angled sinus instrumentation, they allowed surgeons to work in areas previously unreachable from an endonasal approach. These technologic advances made possible additional work on the suprasellar portion of tumors, as noted by Apuzzo et al in the late 1970s and by Fries and Perneczky in the late 1980s.^35,36 However, most neurosurgeons continued to consider the endoscope a replacement for angled mirrors and relegated its use to augmenting the operating microscope.

By the early 1990s, collaboration between neurosurgeons and otorhinolaryngologists resulted in the first reports of purely endoscopic approaches to the sella. Jho and Carrau in Pittsburgh are credited with demonstrating the safety and efficacy of a purely endoscopic approach for pituitary adenoma^37,38 (Fig. 1.8). In a recapitulation of the evolution of microsurgery, they described initial attempts as single-nostril single-surgeon approaches. Nearly simultaneously, Cappabianca, de Divittis, and colleagues in Naples, Italy, reported their initial experiences with the Jho-Carrau technique, taking a rigorously scientific approach to designing improved instrumentation and addressing the limitations of the techniques.^39,40 Soon thereafter, reports from Kassam, Snyderman, and Carrau also described a binasal three-to four-hand technique that restored the neurosurgeon’s ability to perform bimanual microneurosurgery.⁴¹ In the early 2000s, the combined experience of many surgeons allowed exponential improvement in the purely endoscopic technique over a relatively short time. Today, surgeons are able to attack disease from the olfactory bulb rostrally to the odontoid process caudally and as far laterally as the foramen ovale from a purely endonasal endoscopic approach.

Fig. 1.8 (A–C) Schematic and example of operative setup for a purely endoscopic single-nostril endonasal approach to the sella as originally reported by Jho and Carrau. (From Jho H, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 1997;87(1):44–51.)

Conclusion

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