Effect of Surgical Resection on Jugular Foramen Tumors: A Retrospective Study

The complex anatomical structure of jugular foramen (JF) makes a challenge for the diagnose and treatment of this region’s tumors. The purpose of the study was to investigate the effect of surgical resection in patients with JF tumors. A total of 77 patients with JF tumors treated with surgical resection between 2012 and 2021 were retrospectively reviewed. General characteristics, tumor classication, surgical approach and outcomes were retrospectively analyzed. The mean follow-up period was 4.5 years (ranging 0.5-8.5 years). Of the enrolled patients, 63 patients (81.82%) were diagnosed with JF schwannomas. 67 cases (87.01%) of the total patients received gross-total resection. Preoperatively, hoarseness and/or dysarthria served as the most complained symptoms (n=41, 53.25%), followed by swallowing disturbance (n = 37, 48.05%), hearing disturbance and/or tinnitus (n = 32, 41.56%). Postoperatively, a total of 52 patients (67.53%) were without signicant symptoms. Worsened hoarseness and/or dysarthria symptoms were found in 14 patients (18.18%). Besides, 6 cases (7.79%) of the enrolled patients showed worsened swallowing disturbance. 8 patients (10.39%) presented with facial palsy after operation and 3 of them got improvement during the follow-up. Nine patients (12.68%) had tumor recurrence and there was one death (1.3%) associated with surgery during the perioperative period in the cohort. Therefore, surgical resection was an effective treatment of JF tumors with improvements of symptoms and good control of tumor. However, operation on this region was at the risks of worsening cranial nerve decits and death, which needed advance in skull base surgery and rich experience. # JF: Jugular Foramen; § EA-RS approach: Endoscope assisted–retrosigmoid approach.


Introduction
Jugular foramen (JF), located in the posterior cranial fossa, has a complex anatomy structure. This foramen contains important neurovascular structures (e.g., the jugular bulb, sigmoid sinus and lower cranial nerves (CNs)), which makes a challenge for the diagnose and treatment of the JF tumors. Jugular paragangliomas serve the most frequent lesions involving the JF, followed by jugular foramen schwannomas (JFSs) and meningiomas [9]. Other lesions include chordomas, squamous cell carcinomas and temporal bone malignancies [7]. Arising from CNs IX, X, and XI, JFSs represent about 2.9-4% of all intracranial schwannomas [8,17]. Patients with JF tumors may complain about hearing loss, pulsatile tinnitus and CNs de cits symptoms (including facial palsy/spasm, hoarseness and/or dysarthria, swallowing disturbance, shoulder weakness and shoulder weakness). However, operation on the JF region makes the CNs and vessels at high risk. It was reported that 5.7% patients (3/53) with JFSs had a recurrence of tumor postoperatively [3]. Besides, previous study reported that 3.9% patients (4/102) died after the surgery of removing JF tumors [9]. To achieve total resection without injuring the CNs and vessels, advances in skull base surgery, neurophysiological monitoring technology and rich experience are warranted.
The present study reports the surgical outcomes of 77 patients with JF tumors in out center. All the patients were operated by the senior authors between May 2012 and June 2021. Baseline characteristics, tumor classi cation, surgical approach, surgical complications and follow-up ndings are presented.

Patients
Altogether, 77 patients with JF tumors treated with surgical resection between May 2012 and June 2021 were retrospectively enrolled. These patients were operated by the senior authors (NZ and ZH) at the First A liated Hospital of Sun Yat-sen University, (Guangzhou, Guangdong, China). The collected data (including baseline characteristics, tumor classi cation, surgical approach, postoperative complications and follow-up ndings) were analyzed. Preoperatively, hearing tests, neurological examinations, laryngoscopy, magnetic resonance imaging (MRI) and computed tomography (CT) were performed. Digital subtraction angiography (DSA) was performed in three patients with glomus jugulare tumor and two of them underwent vascular embolism operation before the tumor removal. Lumbar drainage was performed to the total patients preoperatively. Intraoperative monitoring included motor evoked potentials, somatosensory evoked potentials, CNs monitoring (VII, IX, X, XI and XII nerve) and brainstem auditory evoked potentials. A CT scan was applied on the rst postoperative day. Follow-up MRI images were performed at 3 months, one year after operation and annually thereafter. Based on the intraoperative ndings, postoperative rstday CT scan and MRI performed 3 months postoperatively, resection degree was determined. Average follow-up period in the present study was 4.5 years (ranging 0.5-8.5 years) and 5 patients lost follow-up. This study was approved by the Ethics Committee of the First A liated Hospital of Sun Yat-Sen University.

Tumor classi cation and surgical approach
Based on the lesion locations, tumors involving the JF were classi ed into four types (type A, B, C, and D), as proposed by Samii, et al (Table 1, Fig. 1) [11]. The most frequent type of JF tumor in this study was type D (40 cases, 51.95%), followed by type A (27 cases, 35.06%), type B (7 cases, 9.09%) and type C (3 cases, 3.9%). We used the transjugular approach and endoscope assistedretrosigmoid approach (EA-RS approach) to remove the JF tumors (Table 1), which were described detailly in previous literatures [2,5,10,16]. In total, sixty-seven patients (87.01%) underwent the transjugular approach for the tumor removal. Ten JF lesions (12.99%) were approached via an EA-RS approach. To reconstruct the cranial base, a technique with three-layers vascularized aps ( rst layer: dura mater (or temporalis fascia and brin glue); second layer: temporalis fascia; third layer: cervical fascia, sternocleidomastoid muscle and temporalis muscle) indicated by Ramina et al [9] was used.

Baseline characteristics
Altogether seventy-seven patients with JF tumors were included in the present study. Baseline characteristics of these patients are listed in Table 2 and/or tinnitus (n = 32, 41.56%), headache and/or dizziness (n = 11,14.29%). Furthermore, there were ve (6.49%) and four (5.19%) patients presented with gait disturbance and hypoglossal nerve palsy, respectively. Facial palsy/spasm and shoulder weakness were respectively found in 3 cases (3.9%) and 2 cases (2.6%) of total patients.

Surgical Outcomes
Postoperatively, 67 cases (87.01%) of the total patients received gross-total resection and 10 patients (12.99%) remained residual ( Table 3). The mean follow-up in the present study was 4.5 years (ranging 0.5-8.5 years) and there were 5 patients losing the follow-up. There were no mortalities during the follow-up. In total, 9 patients (   This was a 68-years old women with a type D JFSs (Fig. 2). Chief complains were right tinnitus and dizziness for one year.
Preoperative MRI showed a right dumbbell-shaped jugular foramen tumor with a size of 22 mm x 38 mm x 49 mm ( Fig. 2A, 2B); Postoperatively, this patient presented pneumonia and newly developed hoarseness. MRI of 3 months after operation demonstrated that the tumor was under gross-total resection (Fig. 2C); MRI images of 1 year after operation showed the tumor was without recurrence (Fig. 2D).

Patient with low-grade malignant tumor of unknown origin
This was a 21-years old man with low-grade malignant tumor of unknown origin involving the JF (Fig. 3). Chief complains were right tinnitus for one year, hearing disturbance and pain in the right ear for 3 months. Preoperative MRI showed a right dumbbellshaped JF tumor with a size of 34 mm x 40 mm x 47 mm (Fig. 3A, 3B); The patient presented CSF leakage, newly developed hoarseness and swallowing disturbance postoperatively. MRI of 3 months after operation showed the tumor had residual (Fig. 3C); MRI of 1 year after operation showed the residue tumor didn't enlarge signi cantly (Fig. 3D).

Patient with malignant solitary brous tumor
This was a 57-years old man with JF malignant solitary brous tumor, WHO III (Fig. 4). Chief complains were hypoglossal nerve palsy for one year, hoarseness for 20 days and swallowing disturbance for 10 days. Preoperative MRI showed a right dumbbellshaped JF tumor with a size of 35 mm x 95 mm (Fig. 4A, 4B); Postoperatively, the patient presented CSF leakage and stable symptoms of hypoglossal nerve palsy, hoarseness and swallowing disturbance. MRI of 3 months after operation showed the tumor was removed totally (Fig. 4C); MRI of 1 year after operation showed tumor had a recurrence (Fig. 4D).

Discussion
It is well known to us that the rst-line treatment for JF tumors is surgical resection. Due to the complex anatomical structure of JF, the optimal result of the surgery in the JF tumors is to remove the tumor completely without any cranial nerve and vessel injuries. With advances in intraoperative monitoring, surgical techniques and rich experience of skull base surgery, these tumors could be removed safely. A previous study enrolled 53 patients with JFSs indicated that vague nerve de cit served the most common presentation, followed by VIII nerve and IX nerve de cits. Besides, 5.7% of the total cases experienced tumor recurrence postoperatively [3]. Sedney et al. manifested that hearing loss was the most common complaint in patients with JFSs (51/81, 63%), followed by vagal nerve de cit (46/81, 56.8%) and glossopharyngeal nerve de cit (30/81, 37%) [15]. In the present study, hoarseness and/or dysarthria were the most common symptoms preoperatively (41/77, 53.25%), followed by swallowing disturbance (37/77, 48.05%), hearing disturbance and/or tinnitus (32/77, 41.56%).
The surgical approach for the tumor removal is based on the surgeon's experience, location and extension of the tumor. It was reported that the infratemporal fossa type A (IFT-A) approach was an optimal approach for removing the JF vascular tumors [7,14]. Petro-occipital transsigmoid (POTS) approach was applied to remove the intra-and extracranial extension lesions effectively, offering well exposure of the JF region [12,13]. Besides, retromastoid approach remained an optical approach for intracranial JF lesions without osseous invasion. Extreme lateral infrajugular transtubercular (ELITE) approach could be used to the intracranial JF lesions with osseous invasion or dumbbell-shaped JF lesions. An intradural and transjugular approach was used to remove the dumbbell-shaped JF lesions with involving the internal jugular vein and jugular bulb [1,3]. Another previous study performed the surgery on Samii classi cation [11] type A and B tumors through suboccipital approach, and used transjugular approach for type C and D tumors [16]. In our center, most patients with JF tumors underwent the transjugular approach for the tumor removal except ten cases (including 8 type A tumors and 2 type D tumors) via an EA-RS approach. Among the nine patients with recurrent tumor, two of them were treated with EA-RS approach and the rest were via a transjugular approach. Through these two approaches and the vascularized aps indicated by Ramina et al [9], only 9 patients (11.69%) occurred with postoperative CSF leakage in the present study. Furthermore, just 10 cases (12.99%) remained residual.
Recently, increasing studies have showed that radiosurgery could effectively control the growth of residual or recurrent JFSs. A multiinstitutional study reviewed the outcomes of 117 JFSs patients underwent Gamma Knife surgery and showed that 53% of the patients had partial remission and 36% had stable tumors. Tumor progression was found in 11% of the patients. The 3-year progression-free survival (PFS) rates was 91% and the 5-year' was 89% [4]. Another retrospective study indicated that 51% of the 92 enrolled patients underwent Stereotactic radiosurgery had a regressed tumor and 13% presented with progressed tumor.
Besides, dumbbell-shaped JFSs were at higher risk of progression [6]. In the present study, a total of 77 patients with JF tumors experienced surgical resection in our center. The most frequent type of JF tumor was type D (51.95%), followed by type A (35.06%), type B (9.09%) and type C (3.9%). Postoperatively, 67.53% cases were without signi cant symptoms postoperatively.
Except one patient (1/77, 1.3%) with type D JFSs dying for the surgery, there were no mortalities during the follow-up. Nine patients (12.68%) occurred with tumor recurrence. Therefore, surgical resection was an effective treatment of JF tumors with improvements of symptoms and good control of tumor. For patients with residual/recurrent tumors, postoperative radiosurgery serves as an optical treatment for the long-term control of tumor.

Limitations
Many limitations existed in this study. First of all, this is a single-center study and the sample size is limited, which is necessary to enlarge to decrease the bias. Besides, our study is a retrospective study and bias may exist during the follow-up. What's more, due to the low incidence of tumor recurrence rate, the factors affecting the tumor recurrence hasn't been analyzed. Lastly, this study didn't compare the difference between the e cacy of radiosurgery and surgical resection.

Conclusion
A total of 77 patients with JF tumors treated with surgical resection in our center were retrospectively reviewed. Our results manifested that surgical resection was an effective treatment of JF tumors with improvements of symptoms and good control of tumor. However, operation on the JF region was at the risks of CNs de cits and death, which needed advance in skull base surgery and rich experience. Data availability The data of this study are available on request due to local (academic) restrictions.

Declarations
Code availability Not applicable.
Ethics approval This study is approved by the Ethics Committee for Clinical Research and Animal Trials of the First A liated Hospital of Sun Yat-Sen University (Guangzhou, China).
Consent to participate Not applicable.
Consent to publication All authors are consent to publish in Neurosurgical Review.
Con icts of interest The authors declare that they have no con ict of interest.    year after operation showed tumor had a recurrence (white arrow).