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Revisiting Surgery in the Current Era of Gamma Knife for Cavernous Sinus Lesions
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.344638
Keywords: Cavernous sinus, cavernous sinus hemangioma, chordoma, cranial nerve, gamma knife, meningioma, pituitary, schwannoma
Lesions in and around the cavernous sinus (CS) have always remained a nightmare to the neurosurgeons. Given the fact that this area houses multiple cranial nerves (CNs), venous lakes, and carotids, the surgery is quite challenging and requires enormous experience. Nevertheless, the evolution of various safe surgical approaches has significantly reduced surgical morbidities with excellent treatment outcomes documented in trained hands.[1],[2],[3],[4],[5],[6] Of late, gamma knife radiosurgery (GKRS) has emerged as an easy alternative to the management of CS lesions with a reasonable clinical and radiological outcome, especially in small, residual, and recurrent lesions.[7],[8],[9],[10],[11],[12],[13] However, with its advent, the enthusiasm for primary excision of such lesions, even the larger symptomatic ones, and those not strictly confined to CS has declined.[8],[9],[11],[12],[13],[14],[15] This partly owes to the lack of surgical expertise passed on to the younger generations. The results after GKRS for CS lesions have been put forth mostly in terms of non-progression of tumor volume, and survival rates perhaps with less emphasis on the actual patients' clinical improvement; the latter which usually manifests in the form of recovery of CN deficits have been relatively under-addressed.[7],[12] Besides, there has been a recent trend towards upfront GKRS, solely based on radiological features without establishing a definitive histopathological diagnosis which at times could be misleading.[8],[11],[12],[13],[14],[15],[16] A diligently performed surgery not only establishes the diagnosis but also brings about rapid improvement in clinical symptoms.[1],[2],[3],[4],[5],[6] Furthermore, in certain pathologies, surgical resection still outweighs the efficacy of primary irradiation.[7],[17],[18],[19] Hence, revisiting the effectiveness of surgery for CS lesions with the current understanding of the pros and cons of GKRS could provide useful insight into the management of these challenging skull base pathologies. With this background, we present our surgical outcomes of patients treated for lesions in and around CS and attempt to identify the role of surgery in the current era of GKRS.
From 2015 to 2019, we studied the data of 32 patients (15 male, 17 female) who underwent surgery for various pathologies of CS lesions. The mean age of patients was 36.3 years (range, 16 to 59 years). The indications of surgical intervention were progressive neurological deficits. The lesions were either primary CS or those that predominantly involved the CS with origin from the sellar/parasellar/petrous region. Their size ranged from 2.7–8.3 cm (mean, 5.2) of which three were ≤3 cm with progressive symptoms. The lesions were approached through fronto-temporo-orbito-zygomatic (FTOZ) craniotomy and extradural transcavernous route. An anterior petrosectomy was added in cases of posterior extension. After dissecting the meningeal and membranous layer, the tumor was decompressed through the corridor already expanded by the tumor. For lesions such as CS hemangioma (CSH), meningiomas, and chordomas, the Kawase/Hakuba approach was more appropriate, and for pituitary tumors, the approach was through the roof of CS after mobilizing the third nerve (Dolenc's). Early in the series, the surgeries were performed without the assistance of intraoperative neuromonitoring. Of late, we have been utilizing this facility, and therefore, could deploy only in very few patients (n = 3). For most CSH, the dissection was carried out initially between the V2 and V3, and further along the plane surrounding the lesion. In chordomas, the V2 and V3 were mobilized by widening the foramina and a subcavernous approach was taken. For pituitary tumors, the dural layers were initially opened. Subsequently, through an intradural trans-Sylvian route, the suprasellar portion was removed; the 3rd nerve was traced and the roof of the CS was cut open and connected with the previously opened extradural corridor. The meningiomas were removed using an already expanded corridor. Usually, these were adherent to the internal carotid artery (ICA) and CN, and such portions were left behind. In schwannomas, after mobilizing the V2 and V3, the tumor was dissected off the normal nerve fibers and traced into the CS. The histopathology of the lesions confirmed after excision were as follows: CSH (8), meningioma (8), trigeminal schwannoma (6), chordoma (3), residual giant pituitary adenoma with CS extension (3) that included two cases of acromegaly and a case of Cushing disease, fungal granuloma (3), and dysgerminoma (1). The patients' clinical, radiological, and treatment outcomes were analyzed. The patients were followed periodically, initially every 3 months for 1 year and then yearly. During their visits, they were assessed for any change in CN symptoms, improvement in pain, and radiological change in the size of the lesion. The patients had a mean follow-up of 16 months (range, 4–36 months). Magnetic resonance imaging (MRI) was performed at 6 months, 1 year, and as and when the patient's clinical condition dictated.
Clinical presentation The most common presentation was various forms of CN deficits [Table 1]. Commonly, the 5th nerve was involved which was seen in 25 patients. Next in frequency were the symptoms related to a paresis of the 3rd and 6th nerve each of which was seen in 17 patients. Eight patients presented with CN 4 deficit. Five patients also had optic nerve dysfunction.
Perioperative events and follow-up The blood loss ranged from 400 mL to 2 L. Gross total excision was achieved in 17 patients. The resection was near total in seven and subtotal in five patients. The latter were patients with meningioma in whom the tumor was left behind owing to adherence to ICA and CN. In patients with near-total removal, though the intraoperative impression of the surgeon was total excision, follow-up MRI showed small tumor residue. In the other three patients with fungal granulomas, only partial excision or biopsy was performed as the intraoperative frozen sections suggested a fungal etiology. These patients were promptly initiated on antifungal treatment. No patient had wound-related complications and cerebrospinal fluid (CSF) leaks. There was no surgery-related mortality in this series. In the immediate postoperative period, eight patients had new-onset and/or worsening of the preexisting CN deficits. However, the majority of these improved at their latest follow-up. The most common added deficit was noted to be 6th nerve paresis. Overall, improvement in CN function was seen in 23 patients. Of these, 13 showed complete recovery (i.e., improvement in all the CN deficits that were present preoperatively) and the others showed partial improvement (at least one or more of the preexisting deficits). Among six patients, the CN function was the same as that of the preoperative status. The time to recovery ranged from 3–12 months. Even smaller tumors showed rapid and excellent recovery of the CN deficits after surgery. Patients with schwannomas, chordomas, and CSH had better clinical outcomes than those with meningiomas [Table 1] and [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5]. The patient with Cushing's disease had tumor recurrence which required redo-excision. Patients with functioning pituitary tumors did not achieve remission and underwent adjuvant therapy. Overall, five patients needed GKRS as adjuvant treatment and showed stable disease. All three patients with chordoma and one with dysgerminoma underwent postoperative radiotherapy. The single patient with Cushing disease received temozolomide and the acromegalics are currently on gonadotropin-releasing hormone (GnRH) antagonists; however, without much benefit. At present, they are being considered for radiation.
Patients with CS lesions frequently present with CN deficits that involve 3, 4, 5, and 6, and the ideal treatment objective would be to ameliorate symptoms along with safe maximal resection. In this respect, surgery remains the preferred treatment for most symptomatic CS lesions, especially large ones.[1],[2],[3],[4],[5],[6],[7],[10],[17],[18],[19],[20] Nevertheless, the surrounding CN and vascular structures preclude complete excision in a few cases.[6],[10],[19],[21] Hence, subtotal removal of the lesions followed by adjuvant therapy is not an uncommonly seen scenario in these patients.[1],[7],[10],[11],[12],[13],[14],[17],[18],[19],[21] Problems with the current practice of replacing surgery with upfront GKRS for CS lesions GKRS has proven to be a useful adjunct to achieve tumor control after surgery.[1],[10] For smaller lesions with minimal symptoms, GKRS is currently being preferred.[8],[11],[12],[13] Recently, the trend is moving towards upfront GKRS even for larger symptomatic lesions.[14],[15] The reason for this shift may be the surgical challenges involved. However, the efficacy of GKRS in terms of improvement in CN symptoms and significant volume reduction, at present is questionable with a lack of long-term follow-up.[3] Besides, GKRS per se is known to cause new-onset CN deficits such as diplopia, trigeminal nerve dysfunction, radiation-induced vascular injury, and carotid stenosis, and is not considered safe.[11],[22] Furthermore, primary GKRS has been advocated for CS lesions solely based on radiology without any tissue confirmation.[8],[11],[12],[13],[14],[15] This approach can be occasionally detrimental. It has been noted that histologically unproven lesions, radiologically presumed to be typical meningiomas and schwannomas have unexpectedly turn out to be infective lesions with poor clinical outcomes.[16],[23] The present series also included three fungal cases with such intraoperative surprise. However, frozen sections obviated the need for radical excision which could have been detrimental in them.[23] CSH compromised the majority of patients in this series. Most patients (about three-fourths) of CSH present with headache and CN symptoms and a realistic expectation would be the recovery of the same.[3],[8],[13] This includes visual deficits, ophthalmoplegia, and diplopia. An ideal treatment goal would, therefore, be a recovery of the preexisting deficits. Regarding the CSH of CS, the optimal treatment has been controversial.[13] Resection, embolization, radiotherapy, and GKRS have been used, each with its pros and cons.[13] With surgery, the complete excision rate has been reported to be >90% although with the concern for intraoperative hemorrhage and new-onset CN deficits.[1],[4] To circumvent these risks, upfront GKRS has been suggested as an alternative therapy.[8],[13],[15] GKRS has an established role as an adjunct for residual lesion and is effective for the control of primary small to medium-sized CSH. Recently, it has been suggested for large CSH (volume, 64.4 cm3) in the form of hypofractionated therapy.[15] However, the efficacy of GKRS as an upfront therapy to reverse CN symptoms is doubtful. In patients with the visual deficit and for large tumors, GKRS may not be suitable due to the potential risk of secondary optic pathway injury.[3],[8] In a multicentric study, though all patients showed a reduction in tumor volume, CN dysfunction improved in only 25%.[8] A meta-analysis suggests that only 15% of patients with CSH (mean tumor volume, 9.6 cm) showed complete resolution of CN symptoms besides the requirement of a higher dose to effect remarkable shrinkage of the tumor.[13] On the other hand, surgical series (both extradural and intradural transcavernous) describe excellent clinical outcome in more than 90% of CSH patients in terms of tumor removal and improvement in symptoms.[1],[3],[4],[6] Though transient CN paresis occurred in most due to handling, it usually recovers. A recent paper that specifically addresses giant CSH (15 patients) has shown an excellent tumor resection rate of 86.7%.[3] Vision improved in all patients except in two who had long-standing complete vision loss. Although a few developed new-onset CN deficits (6th nerve being most common followed by third), most of these patients recovered at their latest follow-up with residual deficit seen only in 13.3% and 6.7%, respectively. For CS meningiomas, total excision has always proven to be difficult due to the encasement of the cavernous ICA and adherence to the CNs.[10] Reported rates of complete excision are about 60–75% with mostly stabilization of the CN symptoms and worsening in few.[21] Even in our series, three patients showed partial/complete improvement and three remained in the same preoperative status. GKRS in CS meningiomas tend to mostly stabilize the neurological status with the improvement of CN occurring only in 5–6%.[12],[14] Besides, a presentation with CN deficits and tumor volume >14 cm3 have been shown to be independent predictors of unfavorable neurological outcome.[14] These data indicate that CN recovery even after GKRS for large tumors is not very promising. Overall, the existing literature suggests that the approach for CS meningiomas should be multidisciplinary with maximal safe resection followed by adjuvant GKRS.[10],[21] In fact, any treatment should be reserved for symptomatic/progressive lesions. In contrast to meningiomas, post-resection recovery in trigeminal schwannomas has shown excellent rates of total excision (90–100%) with good clinical recovery of CN.[2],[5] All the patients in this series showed clinical improvement in their preexisting neurology with no added postoperative deficits. For chordomas, primary surgical resection remains the treatment of choice.[7],[17],[18],[19] The recurrence-free survival is better with the extent of resection, and aggressive tumor removal has been advocated with reported rates of 65–70%.[7],[17],[18],[19] Improvement in CN symptoms occurs after surgical resection, as evident in our series. The existing literature supports a multimodal approach for CS chordomas that includes aggressive resection without compromising the patients' neurological status followed by adjuvant therapy in the form of the proton beam, GKRS, or radiotherapy.[7],[17],[18],[19] The tumor control rate varies from 62–75% after excision followed by GKRS.[7] Surgery remains the first-line management of functional pituitary tumors.[20] As such, the remission rate of functional pituitary macroadenomas with parasellar extension remains relatively less as compared to that of microadenomas (63% vs 81%), and gross total removal has shown better remission rates.[20] Hence, surgical excision appears to be the preferred treatment for functioning macroadenomas with CS extension. Though the CN symptoms improved in our patients, none achieved remission. Principal surgical considerations in CS For CS pathologies, a skull base approach, usually FTOZ and its modifications that provide direct access along with shorter operating distance is fundamental. Given a choice between the extradural and intradural approaches, we would opt for an extradural corridor considering its lack of risks related to temporal lobe retraction and venous contusions. Intraoperative monitoring should be utilized whenever feasible. Besides, understanding certain characteristics of a specific pathology can effectively assist excision with favorable clinical and radiological outcomes. For instance, CSH although a true CS lesion has a pseudo capsule with a potential plane between the lesion and overlying neural structures; the CN are usually displaced and stretched over the tumor.[1],[4],[6] Respecting this plane maximizes the chance of preservation of the CN. The risk of bleeding is a predominant concern in these pathologies and, in fact, a commonly cited reason for non-preference of surgery in CSH. Early identification and coagulation of the feeders from the meningo-hypophyseal trunk of ICA and middle meningeal artery can effectively reduce tumor vascularity. Techniques such as intraoperative hypotension and hypothermia have also been described to lessen the risk of bleeding.[1] Rapid tumor decompression is preferred over en bloc resection by some authors to avoid excessive retraction on the CN. Concerning the CS meningiomas, these are notorious for engulfing the ICA and CN.[10],[21] We practice radical excision of the extracavernous portion; however, with only safe maximal removal of the intracavernous part. By contrast, schwannomas usually displace the neurovascular structures without invasion providing a good plane of dissection, and therefore, at most times are amenable for total excision with excellent clinical outcome.[2],[5] Summary of the major surgical series of common CS pathologies is provided in [Table 2].[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34]
In brief, the approach to a CS lesion should be largely based on the characteristics of the pathology. Rather than subjecting the patients with CS lesions to blanket upfront GKRS, an attempt to establish the definitive diagnosis is suggested. The clinical outcomes, particularly the CN improvement is possibly better and rapid with surgical excision offering a chance of cure rather than a mere lesion control in a substantial variety of CS pathologies. For this reason, we prefer surgical excision for all patients with progressive neurological complaints irrespective of the size of the lesion. For chordomas and schwannomas of CS, surgery remains the management of choice and can be completely excised with very good patient outcomes. Again, for CSH, especially the larger ones and functioning pituitary tumors, excision should be the preferred treatment. In the case of meningiomas, the primary role of resection is safe maximal debulking such that it becomes amenable for adjuvant therapy. This surgical series has a few limitations. Although not the purpose, the study lacks a comparative arm evaluating the effectiveness of GKRS for CS lesions. Most lesions presented here are large. An ideal scenario would be to compare outcomes between similar-sized tumors of the same pathology. However, in our institutional practice, we do not favor upfront GKRS even for smaller lesions unless they are incidental along with characteristic imaging. Hence, the results were not compared. Another study limitation is that our patient cohort is heterogeneous with a relatively fewer number of cases in each pathological category.
We present our surgical outcome of various pathologies involving the CS. Despite the emergence of GKRS as an easy way out, surgery has an unequivocal role in bringing about clinical improvement in many CS pathologies. This spectrum comprises schwannomas, chordomas, large CSH, and functioning pituitary tumors. Most importantly, surgery not only establishes the histopathological diagnosis but may also be curative. Compliance with ethical requirements Informed consent was obtained. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]
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