A retrospective study was carried out to review all patients of GPAs with extensive suprasellar extension, who underwent endoscopic transcranial transdiaphragmatic approach in a single-stage surgery at our institution from 2018 to 2020. Patients’ radiological imaging, visual status, and endocrinological evaluation were assessed pre-and postoperatively. This study was approved by the institutional ethics committee, and written consent was provided by all patients.

The frontobasal interhemispheric approach and pterional approach were utilized in this study on the basis of the tumor growth pattern and neurosurgeon’s preference. The side chosen for craniotomy was decided according to the direction of tumor extension and invasiveness. The frontobasal interhemispheric approach was carried out by the coronal skin incision behind the hairline and a paramedian unifrontal craniotomy. The dural flap was subsequently rotated medially from the base, with the major bridge vein to the midline or superior sagittal sinus being protected. For the pterional approach, a standard frontotemporal craniotomy was conducted with the sphenoid wing being drilled. The dura was opened curvilinearly towards the base, and cerebrospinal fluid (CSF) was released by sharp dissection of the sylvian fissure to expose the tumor adequately in the suprasellar area. The frontal lobe was lifted gravitationally with less retraction force with sufficient CSF drainage. Following craniotomy, we carried out tumor resection within the tumor capsule to avoid harming the perforating arterial branches that supply the optic apparatus and hypothalamus through various corridors of each approach, including the interoptic, interhemispheric, optico-carotid, as well as carotico-oculomotor spaces.

After the complete excision of the suprasellar component of the tumor under a microscope or an endoscope, the dilated diaphragma sellae was exposed. Then, the diaphragma sellae was cauterized using bipolar coagulation, and dissected along the direction from the center to the outside of diaphragma sellae opening to expand the operative corridor into the sella turcica until the residual tumor beneath the diaphragma sellae was clearly visible. Surgical maneuvers are shown in Figure 1. At this point, we introduced a 0° endoscope into the sella fixed with a pneumatic Point Setter (Storz, Tuttlingen, Germany). Under the endoscopic view, the intrasellar tumor was resected in order from the front side to the bilateral sides of the sella turcica by using a combination of curved curettes and suctions. During the resection of the tumor located posteriorly within the sella turcica, a 30° endoscope was placed through the diaphragm sellae opening to help identify and preserve the pituitary stalk. In this way, the intrasellar tumor can be completely removed under a clear endoscopic view in a single-stage transcranial surgery.

The detailed characteristics of all patients are summarized in Table 1 . All patients (N=4; 3 men and 1 woman; mean age, 57 years) exhibited visual dysfunction. Two patients suffered from dizziness. Hydrocephalus was present in 1 case. All patients had no prior surgery. All tumors were nonfunctioning pituitary adenomas and exhibited a multilobular shape. Based on the preoperative MRI, the mean maximum diameter was 59.7 mm (range from 55.1 to 65.1 mm). The suprasellar extension was evaluated by assigning Hardy-Wilson (12) and Goel grades (4). According to the Hardy-Wilson classification, we found 3 grade II and stage D tumors, and 1 grade III and stage D tumor. According to the Goel classification, all tumors belonged to grade IV.

Postoperative results are summarized in Table 2 . The rate of tumor resection was categorized as gross total resection (GTR, 100%), near-total resection (NTR, 90%-100%), subtotal resection (70%-90%), and partial resection (<70%) according to Juraschka et al. (5). In this study, GTR was attained in 3 patients, and NTR in 1 patient. The operation duration ranged from 5.75 to 8 hours. Particularly, 3 patients had markedly improved postoperative visual function. The other patient had a stable visual function. The endocrinologic assessment revealed that 1 patient developed persistent diabetes insipidus, while another had a deficiency of thyroid-stimulating hormone along with adrenocorticotropic hormone. Both patients required hormone replacement therapy. A serious complication occurred in 1 patient who suffered an epidural hematoma that underwent decompressive craniectomy by removing the bone flap. During the follow-up period (8 to 63 months), no obvious tumor relapses were evident in all these cases.

The treatment goal of GPAs is mainly complete resection, partial resection plus adjuvant radiotherapy, or a combination of surgery, and radiotherapy along with observation. Surgical resection of GPAs is still very challenging because of their enormous size, multilobular shape, and irregular extension into the cavernous sinuses or suprasellar area (1, 13, 14). Each extension has its anatomical characteristics that should be discussed separately. In particular, lateral extensions greatly make surgical access and resection difficult. The postoperative morbidity and mortality of GPAs are mainly caused by damage to perforating arteries or subsequent bleeding from the residual tumor. To prevent postoperative apoplexy, radical resection of the tumor, including GTR and NTR, should be the primary surgical goal. Thus, it is critical to determine the optimal surgical approach to maximally resect GPAs.

Both transsphenoidal and transcranial approaches have been conventionally employed in the surgical treatment of GPAs for many years. Because the suprasellar portion of tumors often descends into the field of operation by the force of gravity following decompression of the intrasellar tumor, the transsphenoidal approach is usually preferred for the majority of GPAs over the transcranial approach (4, 15). During the last decades, the endoscopic endonasal approach enabling removal of GPAs has been increasingly explored, because it offers a detailed, panoramic visualization and wider access to the operative field through the angled endoscopes (3, 16–18). In addition, supplemental imaging using intraoperative MRI, which may detect unanticipated residual tumors and identify the tumor margins in real time, may also improve the rate of GTR during the same surgery (19). Furthermore, the extended endonasal endoscopic approach, which enables removing the bone of tuberculum sella along with a portion of the planum sphenoidale, coupled with exposing the ventral and medial cavernous sinuses, has remarkably improved the total resection rate of GPAs and postoperative visual function (7). However, tumor excision via this single approach may be challenging when the tumor extends outside the surgical corridor. Previous literature also suggested that this approach may have limited applications in the treatment of multilobular GPAs because of the absence of extensive linkages between the tumor components (3). Aggressive tumor resection under inadequate visualization may cause injury to adjacent critical structures, as well as lead to severe surgical complications and poor patient outcomes. In addition, postoperative cerebrospinal fluid (CSF) leakage is the most frequent complication of the extended endoscopic endonasal approach. Although the rate of CSF leakage was reported to be reduced to 7.4% after a vascularized nasoseptal flap was routinely used (3), the technical point linked to the difficult multilayer reconstruction of the skull base defect has always rendered the extended endoscopic endonasal approach as a relative challenge.

Considering this complicated situation, various surgical procedures have been reported to optimize resection of GPAs with significant suprasellar and anterior extension, including simultaneous combined surgeries and two-staged surgeries (14). In reality, various types of combinations have been documented: microscopic transsphenoidal approach–microscopic transcranial approach (8), endoscopic transsphenoidal approach–microscopic transcranial approach (10, 20, 21), endoscopic transsphenoidal approach–endoscopic transventricular approach (22), microscopic transsphenoidal approach–endoscopic transventricular approach (23), endoscopic transsphenoidal approach–microscopic transventricular approach (24), and endoscopic transsphenoidal approach– endoscopic supraorbital keyhole approach (11). The greatest advantages of these simultaneous combined surgeries are not only to increase the degree of tumor excision, but also to support safe tumor removal and minimize postoperative bleeding of the residual tumor. However, the potential disadvantages of these simultaneous approaches included the increased risk of infection, invasiveness, and extra craniotomy-linked complications. Moreover, these procedures require twice as many neurosurgeons and twice as many instruments, for instance, microscope and endoscope, which are not available at most institutions.

Some surgeons prefer a 2-staged surgery for difficult GPAs (6, 14, 25), including the utilization of the transsphenoidal approach at first and subsequently the transcranial approach after several months, or vice versa. The prospects of a radical excision are remarkably diminished when more than half of the suprasellar region of the tumor is out of the line of transsphenoidal vision, especially when the tumor consistency is unfavorable (17). Large Hardy’s stage C tumors are a nonhomogenous group of tumors, and several authors have advocated for a staged surgery in these difficult cases to enable the suprasellar residual to descend into the sella (17). The 2-staged surgery procedure also provides a higher rate of tumor excision relative to the single-stage approach. However, the patient will have to undergo surgery twice, and the incidences of postoperative bleeding from the intentionally remaining tumor cannot be avoided.

Although most pituitary adenomas as well as some GPAs can be treated via a transsphenoidal procedure, parasellar tumors that are fibrous and adhere firmly to critical structures or that extend far laterally further than the internal carotid artery are still very difficult to remove completely with a transsphenoidal procedure alone. Even though transcranial surgery is usually associated with an elevated risk of postoperative pituitary dysfunction, morbidity and mortality (26), this might be confounded since the transcranial approach is often preferentially selected for more complicated tumors with extensive lateral or anterior extension. The transcranial approach has its own advantages, which are quite useful to reach the lateral extent of tumors, and decompress the neurovascular structures, especially the optic apparatus (26). In fact, the transcranial approach still plays an essential role in about 1-10% of GPAs, and neurosurgeons who deal with numerous cases of pituitary adenomas annually may need to utilize this procedure fairly frequently (25). Shen et al. concluded ten indications for transcranial approaches according to the literature (27), which are 1) tumor mainly located in the suprasellar region and/or the sella turcica was too small and narrow; 2) dumbbell-shaped or hourglass-shaped tumors with a constriction at the level of diaphragma sellae opening; 3) suspicious fibrous consistency; 4) irregular shape with anterior, middle, posterior cranial fossa, or intraventricular extension; 5) brain invasion with cerebral edema; 6) the presence of ectatic carotid arteries projecting toward the midline or coexistent aneurysm; 7) encasement of subarachnoid arteries; 8) postoperative apoplexy in suprasellar residue following transsphenoidal operation; 9) current sinusitis making a transsphenoidal approach inappropriate or previous transsphenoidal surgery; and 10) uncertainty regarding the diagnosis. In our study, all patients had more than 4 of above characteristics. Standardized craniotomies, such as fronto-lateral, pterional and basal midline craniotomies that are close to the skull base, are performed depending on the tumor’s localization to avoid brain retraction. The carotid artery and its branches, as well as the optic nerves and chiasm, may be microscopically dissected with sufficient space created by the drainage of CSF. The transcranial approaches enable the intracranial component of a pituitary tumor to be resected with relative radicality. The major challenge, however, is the risk of damaging the surrounding structures that must be carefully exposed and dissected. In addition, it is difficult to clearly judge whether there is residual tumor in the sella turcica under the narrow microscopic view.

In this study, we propose a new surgical technique, which is to dissect the sella diaphragm and resect the intrasellar tumor by endoscopic transcranial transdiaphragmatic approach after removal of the suprasellar portion of GPAs. This strategy may help to identify residual tumor within the sella, which can improve the tumor total resection rate, minimize brain retraction, and reduce the possibility of residual tumor apoplexy. In our cohort, we achieved gross total resection in 3 patients, and near total resection in 1 patient. None of the patients had postoperative apoplexy. In addition, this technique eliminates the need for a combined or secondary operation, which is helpful to reduce surgical trauma. Particularly, compared with the endoscopic endonasal approach, the endoscopic transcranial transdiaphragmatic strategy may avoid complicated skull base reconstruction and reduce the risk of CSF leakage and secondary intracranial infection.

Our study’s limitations include its retrospective aspect and the fact that the cohort was relatively small to make definitive conclusions. Further studies involving more case series are necessary and important to confirm the safety and efficacy of the current approach. This approach needs to overcome all the challenges of resecting GPAs with multiple lobules, extensive invasion, and vascular encasement. This approach is inappropriate for GPAs with a shorter sella turcica length (distance from tuberculum sella to the tip of the dorsum sella). Besides, simultaneous mastering the manipulation of both the microscope and the endoscope requires extensive training and a long learning curve, because dissection of the giant tumors under an endoscopic view remains a great challenge for most neurosurgeons.