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Table of Contents    
Year : 2020  |  Volume : 68  |  Issue : 7  |  Page : 33-38

Evolution of Pituitary Surgery

Department of Neurosurgery, Bombay Hospital Institute of Medical Sciences, Mumbai, Maharashtra, India

Date of Web Publication24-Jun-2020

Correspondence Address:
Dr. Chandrashekhar E Deopujari
Room No 114, MRC Building, Bombay Hospital, 12, Marine Lines, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.287673

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 » Abstract 

Pituitary tumors may well be the most common brain tumors with a mean incidence of 16.7%. Even small tumors become symptomatic when they arise from functioning cells and produce devastating effects on the body. The nonfunctioning tumors may become quite large before producing symptoms due to raised intracranial pressure or mass effect on the surrounding structures, most commonly, the optic apparatus. Many of them remain asymptomatic through life. Evolution of pituitary surgery is testimony to the advances in diagnostic and surgical techniques in neurosurgery and improved understanding of 360° of surgical skullbase anatomy as well as the need to provide not only immediate good postoperative results but also a long-lasting relief. Despite considerable advances in medical treatment as well as focussed radiation techniques, surgery remains the primary treatment in many of these tumors. Visual improvement, hormonal cure, avoidance of hypopituitarism, and neurological deficit remain immediate goals of surgery. Long-term cure or remission may require a multidisciplinary approach.

Keywords: Endoscopic skullbase surgery, pituitary tumors, transcranial approach, transsphenoidal surgery

How to cite this article:
Deopujari CE, Shaikh ST. Evolution of Pituitary Surgery. Neurol India 2020;68, Suppl S1:33-8

How to cite this URL:
Deopujari CE, Shaikh ST. Evolution of Pituitary Surgery. Neurol India [serial online] 2020 [cited 2021 Jul 29];68, Suppl S1:33-8. Available from:

Key Message: The discovery of pituitary disorders, their causal relationship with pituitary tumors and surgical approaches to these tumors developed almost simultaneously towards the turn of 19th century. Harvey Cushing's remarkable clinical skills in describing what is known today as Cushing's disease, his curiosity to link acromegaly to pituitary tumor by opening the giant Irishman's (Charle's Byrne or O'Brien from Littlebridge) skull at the Hunter's museum in London several years after his death and his excellent record at sublabial transsphenoidal as well as transcranial surgeries even before the advent of steroids and antibiotics have established an important benchmark for neurosurgical contribution to pituitary diseases. Today, we have well-defined diagnostic methods and therapeutic options in our armamentarium and surgery still have an important place in management of these tumors.

The incidence of pituitary tumors in the community is quite high (mean 16.7%) as reported in autopsy (14.4%) and radiological (21.6%) studies.[1] Surgery for pituitary tumors has evolved over the last century and can be safely advised for selected patients of functioning as well as nonfunctioning adenomas. Neurosurgeons have played a major role in diagnosis as well as treatment of pituitary disorders with a disease named after a pioneer neurosurgeon (Cushing's disease) [Figure 1]. Pituitary tumors and their surgical approaches were a keen source of interest and study at the end of the 18th century and beginning of the 19th century. Several landmark papers have subsequently described further progress in the 20th century for pituitary surgery and, more recently, especially in this millennium, the development of endoscopic technique in transsphenoidal surgery.
Figure 1: Cover page of the monograph published by Harvey Cushing in 1912 containing description of the first patient of Cushing's disease seen by him

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 » Discussion Top

Sir Victor Horsley should be credited with the first surgical approach in 1889 as described in the annual meeting address of the British Surgical Association in 1906. This was for a presumably cystic pituitary tumor, by transfrontal route, which he thought as inoperable and abandoned the procedure.[2] The patient died sometime later. At autopsy, the frontal lobe had become so very soft, that he decided to do the next case by trans-temporal route in 2 stages. Caton and Paul thus performed a temporal craniotomy on Horsley's suggestion for pituitary tumor with acromegaly but without success.[3] Horsley's personal series consisted of 10 cases whose surgical steps and pathology was neither reported by him nor published in the literature. Remarkably, it was only recently that surgical details for these surgeries have come out of oblivion after the book “La Patologica Chirugica dell, 'Ipofisi,” written by Giovanni Verga, an Italian assistant professor of anatomy in 1911, was studied. These records stated that in his pituitary cases, a couple of these were craniopharyngiomas on pathology, which would thus make Sir Victor Horsley one of the earliest to perform craniopharyngioma resection as well.[4]

Oskar Hirsch, a pioneer of endonasal surgery starting in Vienna and later continuing his transsphenoidal pituitary surgery working in the United States, described the treatment of pituitary tumors in 5 phases till 1956.[5]

  • First Period: Search for a Method of Reaching Pituitary Tumors (1904–1910): During this period cranial as well as transsphenoidal approaches were employed. The pioneering trials of this period were marked by high mortality
  • Second Period: Efforts to Reduce the Operative Risk (1910–1920): Cranial surgery by Cushing and Transsphenoidal surgery by Hirsch striving for the improvement of both types of surgery to reduce morbidity and mortality
  • Third period: Postoperative radiation (1921–1931): Radium implantation for lasting results
  • Fourth period: Publication of long-lasting results (1932–1944)
  • Fifth period: Antibiotic Era (1945–1955): Considerable reduction in mortality and morbidity.

Some do argue that an Italian Physician, Davide Giordano set the precedent for transsphenoidal approach by performing the transmalleolar nasal approach for pituitary gland in 1897 on cadavers.[6] F. Krause from Berlin accessed the sella by transfrontal route in 1905.[7] However, the description of the tumor suggested a tuberculum sellae meningioma. Hermann Schloffer, an Austrian Surgeon, is considered the pioneer of transsphenoidal surgery. This was first achieved by a lateral rhinotomy approach in 1907 (Unfortunately the patient expired two months later). This year remains etched in history and his legacy was revisited in 2007 at the centenary celebrations in Vienna [Figure 2].[8] Immediately after Schloffer's attempt, Chiari developed a transethmoidal approach to make the exposure more superficial.[9] Hirsch thereafter started endonasal surgery in Vienna in 1910 without an external incision and used a stepwise approach successfully since then.[10]
Figure 2: Program cover of the Schloffer conference (meeting of the International Society for Pituitary Surgery (ISPS) celebrating 100 years of transsphenoidal pituitary surgery in 2007 at Vienna, Austria

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In the United States, Halstead probably performed the first transsphenoidal surgery with Kanavel in 1909 by removing the turbinates as well as the septum and then opening sinuses through a sublabial incision and curetting out the pituitary tumor.[11] Kanavel modified the approach by an incision under the nares, cutting the cartilaginous septum at the base and introducing a nasal speculum.[12] Harvey Cushing further modified this by the sublabial approach and mucosal dissection to approach the sphenoid sinus after cartilaginous septal resection which soon became the standard operation[13] and was used by him successfully in over 200 cases. Frazier presented frontal craniotomy with orbital roof removal for extradural approach to this region in 1913[14] and Heuer used the pterional approach in 20 cases as presented by Walter Dandy in 1918 in his absence.[15]

Eventually, Harvey Cushing shifted to the subfrontal transcranial approach.[16] This was mainly due to limitation in resecting large tumors, especially when modern imaging showing the full extension of the tumor was not available as well as due to the more satisfactory decompression of optic nerves under vision in craniotomy. This shift, contributed also by the preference of Walter Dandy for the transcranial approach, mirrored the gradual decline in popularity of transsphenoidal approach in the field of neurosurgery in US as well as Europe. The mortality in over 200 cases of transsphenoidal surgery was 5.6% in follow up of Cushing's patients.[17] Dandy thereafter continued the transcranial pituitary surgery in over 287 patients. Hirsch also showed a mortality of less than 6% in his series of 413 cases operated transsphenoidally, dropping to 1.5% after the introduction of antibiotics.[18] Frazier's series of 53 transsphenoidal operations had also shown a mortality rate of 4.5% in 1926.[19] To prevent recurrences, Radium implants and radiation therapy then was introduced and gradually popularity of transsphenoidal surgery started waning, especially in North America.[20],[21]

Despite the wavering interest in transsphenoidal approach, due to the expertise and success of Harvey Cushing and Walter Dandy in transcranial approaches, ironically, it was a student of Cushing, Scottish Neurosurgeon Norman Dott, who kept it alive in Scotland. Inadequate visualization was however still considered to be the nemesis of this approach. Norman Dott introduced illuminating nasal speculum in 1956. The torch was then passed on to one of his most innovative fellow from France, Gerard Guiot who is credited with being the first Neurosurgeon to use the endoscope in transsphenoidal approach in 1961 and also in 1965, to incorporate intraoperative fluoroscopy. Subsequently, to build upon this aspect, Jules Hardy from Canada, who studied transsphenoidal surgery under Guiot, brought binocular microscope and microsurgical excision to the fore when he started working in Montreal. He is credited with defining the concept of microadenoma and introducing selective adenectomy for functioning tumors, improving their cure rates.[22] These 3 Surgeons are rightly heralded as being responsible for not only keeping transsphenoidal surgery alive but also for pushing the subsequent generations to innovate and improve upon the existing approach.[23] Hardy's categorization of pituitary adenomas based on the sellar floor status and suprasellar extension was the first classification of its kind and was described in 1976.[24] Jules Hardy also had a huge influence on Indian neurosurgery when, as a Commonwealth Fellow, he visited several centres in India to teach and start transsphenoidal surgery programmes in 1982 [Figure 3]. Soon thereafter, Huw Griffith from England described a more direct transnasal microscopic approach[25] which was adapted by A. K. Banerji at the AIIMS, New Delhi and several other centres in India.
Figure 3: Dr. Jules Hardy (Left) and the senior author at the ISPS Schloffer meeting of 2007 in Vienna, Austria

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There was a lull in the development and technical progress in the transsphenoidal approach for much of the 1970s and 80s. A landmark paper which came in 1993 by Knosp et al.[26] helped define cavernous sinus invasion by large pituitary tumours and thus led to a grading system, based on which, resection rates could be studied.

Thereafter, Roger Jankowski, an otorhinolaryngiologist from France, published a series of 3 cases of pituitary adenomas with well pneumatized sphenoid sinuses excised via the endoscopic endonasal transsphenoidal approach.[27] This was followed by the first large series of 50 patients in 1997 by Jho et al. from Pittsburgh, USA.[28] A new era started in the field of exclusive endoscopic endonasal surgery since then. Focus shifted back to technical advances, expansion of the available surgical corridors, improved visualization and optics. We presented our experience of endoscope assisted surgeries in the first 37 cases at the 1st international congress of Endoscope assisted neurosurgery at Frankfurt, Germany in 1998.[29] Experience with larger case series with outcomes led to reaffirming its advantages, convincing the surgical fraternity of its merits.[30]

Further technical development

To facilitate the persistent issues of hazy vision due to the collection of blood and bone dust, modifications such as irrigating outer sheath were introduced by Cappabianca, Kubo, and others.[31],[32] Oldfield in his 2006 paper describes the transition of pituitary adenomas from being devoid of a capsule when less than 1 mm in size, to developing a pathological reticulin pseudocapsule as it grows larger than 3 mm. Use of this capsule surgically helps in obtaining a gross total resection.[33] Maximal chances of remission and functional outcomes has been shown to occur in patients with selective adenectomy[34] and if that fails then in those who undergo hemihypophysectomy.[35] Microscopic dural invasion can be a predictor for tumor residue and may be responsible for remission even after extracapsular excision[36] and is seen more commonly in cases with suprasellar extension. Hence tumours limited to the sella are more amenable to achieve complete adenectomy.[37]

Cavernous sinus invading tumours are best explored using endoscopic endonasal approach since it provides for direct assessment of the medial wall.[38] However, soft, suckable invading tumours may be more amenable to excision rather than the firm, nonsuckable ones for whom radiotherapy may be a safer and better treatment option.[39] The proximity of cavernous sinus to the sella and the associated risks of vascular injury led to studies detailing intraoperative corridors for excision.[40] The Knosp classification too was further modified in 2015 to include superior and inferior cavernous sinus invasion.[41] Safety profile has been further improved by description of endoscopic anatomy based classification of cavernous sinus invasion.[42]

In 1987, Weiss had proposed the expansion of the traditional microsurgical transsphenoidal route by removing the tuberculum sellae and part of planum sphenoidale.[43] Subsequently, Kassam et al. described papers detailing the 360° access to skullbase anatomy via the endonasal route.[44],[45],[46],[47],[48] Probably the best description of internal carotid anatomy from an endonasal perspective was described by the Pittsburgh group in 2008[49] and is an essential reading for anyone wanting to cross the carotid during dissection. The same group then described a large series of 800 cases by the binostril approach signifying shift from the previously preferred Uninostril approaches.[50] This further expanded the armamentarium of safe endoscopic approaches to suprasellar extensions as well as for other suprasellar[51] and petrous apex lesions by other groups.[52] Intraoperative adjuncts which helped in extended surgery include Doppler, curved suctions, 30, 45, and 70° endoscopes and neuronavigation.[53]

High rates of CSF leakage remained a major deterrent for the acceptance of these approaches. Though fibrin glue had reduced the bleeding and CSF leak rates,[54] the watershed moment came through in the form of a pedicled nasoseptal mucosal flap repair named as the Hadad-Bassagasteguy flap after the Surgeons who first fashioned them.[55] Today it is undoubtedly one of the most widely practised methods for reconstruction of skullbase endonasally, leading to an acceptable risk of CSF leakage. This has been possible even in infants.[56] Apart from the HB flap, complex or high-pressure CSF leaks intraoperatively can also be effectively tackled with a multi-layered repair consisting of autologous fat, fascia, and mucoperiosteum.[57]

In 2009, one of the earliest meta-analysis and systematic review of literature pertaining to endoscopic pituitary surgery concluded it to be a safe approach with good short-term results.[58] Literature also shows that binostril approach has a lesser incidence of complications and better outcome as compared to Uninostril approach.[59]

Hemostasis is imperative to achieve a clear field of vision in pituitary surgery. The sources of bleed may be are arterial, venous, mucosal surface, etc. Apart from carotid bleeding, which may require intervention, most other bleedings can now be managed well. The traditional local hemostats, viz., oxidized cellulose, gelatine sponge, collagen, etc. and the electrosurgical methods for bipolar coagulation with specially designed bipolar forceps, provide a comprehensive method to control bleeding.[60],[61],[62] The visualization with these traditional hemostats may be compromised and various types of tissue sealant glues and flowable hemostats derived from human and animal sources have been described for topical application which are quite useful in these procedures. Comparison of microscopic and endoscopic approaches for pituitary surgery shows that though resection rates and outcomes are comparable between the two, incidence of complications is lesser and patient comfort is better with endoscopic surgery. However, the incidence of vascular complications seems to be higher with endoscopic approach,[63],[64],[65],[66] especially in extended approaches.

Endoscopic endonasal pituitary surgery in pediatric patients is now considered as a standard line of care in selected cases with a few centres elaborating its effectiveness after having combated the traditional problems of variations in sinus development and small nostrils and reconstruction issues.[67],[68],[69] An interesting insight has been offered by Dhananjaya Bhat on the concept of “learning curve” which is often discussed in endoscopy.[70] It seems inevitable, with the widespread applicability of endonasal surgery, that this idea will soon become outdated with each trainee and surgeon being ingrained with the necessary skills at the very outset of his career. A prospective study of 1,000 consecutive endonasal pituitary cases from Weil Cornell, USA offers another perspective on the learning curve that it need not necessarily plateau after the first few cases and in fact continues to improve throughout a surgeon's career.[71]

Though transsphenoidal route, either by micro or endosurgical method has become the standard of care for majority of pituitary tumors, a few situations still demand transcranial surgery. A Giant tumour with vascular encasement and fibrous consistency may necessitate a transcranial approach for optic decompression either combined with transsphenoidal approach or subsequently and occasionally may be offered first. Pterional and frontal interhemispheric approaches are preferred.

Future perspective

3D endoscopy is now common at many centres and published experience comments on the better depth perception it offers without significantly altering operative time.[72],[73]Robotic arms are being studied in endonasal surgery and early results have shown them to reduce surgeon fatigue providing better precision.[74] To reduce the nasal damage and achieve greater space to manoeuvre, a specialized nasal retractor has also been described recently by Chandra PS et al. from India.[75] With the rapid development in technology and optics, these aspects of endonasal surgery, viz., malleable endoscopes, 3D/4K/8K optical systems, artificial intelligence navigation systems and robotic approaches may not be too far away from becoming the well accepted norm applied in every pituitary surgery.[76],[77]

In a resource limited country, a dedicated pituitary surgical team may help offset the high cost involved in multidisciplinary treatment of pituitary disorders.[78]

 » Conclusion Top

The beginning of pituitary surgery and the changing neurosurgical approaches have been described with several landmarks along the way. The debate between transsphenoidal and transcranial surgeries seems to have largely settled. The transsphenoidal approaches have become more refined over recent years. The expanding applications of skullbase endoscopy have been discussed with focus on new anatomical studies and technological advances. These advances along with improved 360° anatomy knowledge of the skullbase has empowered us to use surgical skills for optimum results in surgery for pituitary tumors and opened a big pathway to midline skullbase pathologies.

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Conflicts of interest

There are no conflicts of interest.

 » References Top

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