Combined simultaneous transcranial and transsphenoidal resection of large-to-giant pituitary adenomas

Large and giant PAs are difficult to remove safely. The operative mortality rates have been reported to be as high as 25% for transcranial resection and 14% for transsphenoidal resections [31]. Advancement in neurosurgical techniques has led to an improvement in outcome. Sinha et al. [28] reported the surgical outcomes of 250 patients with giant PAs. Near-total (>90%) tumour removal was achieved in 74% and improvement of vision in 53% of patients. The mortality and morbidity rates were 4.4% and 14%, respectively. Xue-Fei et al. [35] treated 54 patients with large PAs using a variety of surgical approaches and achieved complete tumour removal in 21% of cases. The peri-operative mortality rate was 7.9%. In another series of 111 patients, Mortini et al. [21] reported a mortality rate of 2.7%. The incidences of ‘major’ complications (e.g. cranial nerves, hypothalamic and vascular injuries, CSF leakages and tumour haemorrhages), and ‘minor’ complications (e.g. endocrinological) were 18% and 26%, respectively. Using the same categorization, the incidences of ‘major’ and ‘minor’ complications in our present series were comparable at 8.3% and 25%, respectively. The extent of removal in our series, however, was comparatively lower, which was probably due to our conservative approach towards tumours within the cavernous sinuses.

The transsphenoidal approach is the treatment of choice for the majority of PAs. But for tumours that arise in or extend into the suprasellar region, transsphenoidal surgery is generally contraindicated when there is a normal-sized sella turcica, normal pituitary function, or adherence of the tumour to major intracranial structures [6, 12, 14, 18]. A tumour that is fibrous in consistency or has an hour-glass configuration may also be difficult to remove completely with a single transsphenoidal procedure [20]. Lumbar subarachnoid saline or air injection may be used to facilitate the descent of the suprasellar tumour bulk into the sella, but the method is effective only in a subgroup of patients [29, 37]. In a prospective study, Honegger et al. [11] demonstrated that the vertical intracranial extension, and an irregular or multilobular configuration, were significant and independent predictors for incomplete resection. To address this, the two-staged transsphenoidal approach has been advocated, in which, after the removal of the intrasellar tumour component, the suprasellar residual tumour was given time to descend and then removed by a second-stage transsphenoidal procedure [1, 26, 31]. The disadvantages of this approach include the need for two operations and the potential risks of tumour swelling and haemorrhages after the first-stage surgery.

The introduction of endoscopic transsphenoidal surgery has revolutionized the treatment of sellar tumours [4]. It has been shown to be safe and effective, and is now an arguably standard therapy for the majority of PAs. But despite the vastly improved illumination and visualization provided by the use of endoscopes, a giant or invasive PA is amenable to a single-stage removal by a limited number of experts only [30]. Wang et al. [33] reported an 80% total resection rate in a series of 64 patients without mortality or tumour recurrence. Similarly, Sanai et al. [27] reported a GTR rate of close to 50%, with no incidence of CSF leakage, new panhypopituitarism or worsening of vision. Nakao et al. [23] treated 43 patients using the endoscopic endonasal approach and an intracapsular resection technique. Gross total removal was achieved in close to 50% of cases and there was no major complication. While the indications for endoscopic pituitary surgery are expanding, its use and limits for the treatment of huge PAs are yet to be defined. The extended endoscopic transsphenoidal approach, in particular, is a technically demanding technique. It requires specialized and advanced training, and may not be readily acquired by surgeons without the necessary case volume [4].

For many, the transcranial approach continues to play a role in the management of PAs inaccessible from the transsphenoidal route alone [36]. When compared with the transsphenoidal approach, there is a trend towards greater visual improvement, but the benefit may be offset by a greater risk of post-operative pituitary dysfunction [22]. The disadvantages of the transcranial approach include the amount of brain retraction required and the limited visualization of the intrasellar area [¹⁵]. In our experience, a transcranial resection of vascular tumours may also be associated with significant bleeding within the intradural space. This may further obscure the surgical view, and potentially increase the risks of brain swelling and hydrocephalus. One of the advantages of our simultaneous combined approach is that tumour bleeding would occur predominantly on the transsphenoidal side. The transcranial surgeon only serves to deliver the tumour bulk towards the sella, and to protect the intradural structures.

Loyo et al. [19] first described the combined supra-sellar and infra-sellar approach in 1984 for the resection of very large PAs, and advocated it as superior to either the transsphenoidal or the intracranial approach alone. Case reports on the use of the ‘above and below’ approach for a large craniopharyngioma [16], and a PA with lateral ventricle extension have been described [10]. To our knowledge, there are two reported case series on the combined approach for large-to-giant PAs. Alleyne et al. [2] reported a GTR rate of 40% in a cohort of ten patients. More than half of those who presented with pre-operative visual field loss experienced complete recovery. Permanent DI occurred in 20% of patients. In D’Ambrosio et al.’s series [7], GTR was achieved in six out of 11 patients (55%). Seven patients (64%) experienced visual improvement post-operatively and no major complication occurred. Panhypopituitarism was observed in four and persistent DI in two patients. The authors of these two series focused mainly on early operative outcomes but not tumour control. Our present study yielded similar early outcomes. In addition, we were also able to demonstrate satisfactory medium-term tumour control. Admittedly, the use of up-front fractionated external irradiation, instead of radiosurgery, in our series warrants careful scrutiny in view of the former’s potential side-effects. This is a limitation of our treatment paradigm that needs to be improved.

Conceptually, we consider this technique to be a posterior extension of that of craniofacial resection for anterior skull base tumours, in that lesions which occupy two adjoining skull base compartments are best approached simultaneously from both compartments for maximal tumour removal and safety [15]. Although pathologically very different, these two disease groups may exhibit similar morphological features, such as close adherence to intracranial structures, irregular configurations and extensive skull base destruction. Technically, we favour the anterior inter-hemispheric route for the transcranial phase because it provides a better view of the parasellar region bilaterally. The subfrontal or pterional route, on the other hand, requires some head-turning, which may potentially disorientate the transsphenoidal surgeon.

One of the main goals of surgery for huge PAs is optic nerve/chiasm decompression, for which the combined approach appears to be a safe and effective method. The main advantages of our technique include the need for only one procedure, the protection offered by the transcranial surgeon, and the avoidance of complications potentially caused by any residual suprasellar tumour bulk. The main disadvantages include the involvement of two operative fields, the doubling of staff and instruments required, the long operating time, and the potential complications of a craniotomy. The need for two operating microscopes, however, may be obviated by the use of endoscopes for the transsphenoidal phase of the procedure. More recently, an alternative ‘above and below’ approach has been described by several authorities for the treatment of PAs with significant third ventricular extensions. It uses a simultaneous endoscopic transsphenoidal-transventricular technique and therefore obviates the need for a craniotomy [10, 24, 25].

In terms of tumour control, stage C (grossly displaced third ventricle) and D (intracranial parasellar extension) are potentially amenable to total removal with our technique; stage E (extradural parasellar extension) lesions may require a more extensive extradural approach. However, being a retrospective case series, this report may suffer from case selection bias, suboptimal data collection, and the lack of a control cohort for outcome analysis. The optimal treatment of large-to-giant PAs is likely to require a more tailored approach, based on individual patients’ conditions and the surgeons’ experiences and abilities. A multi-modality management strategy should be adopted to take full advantages of the benefits provided by surgery and radiotherapy [8]. The use of intra-operative MRI may also significantly improve resection rate and safety [3]. Our combined approach represents only one of the many surgical strategies that can be used in dealing with these challenging PAs, particularly when expertise in endoscopic surgery is unavailable.