Combined Endoscopic and Exoscopic Resection of Intracranial Epidermoid Cysts

Li Chuzhong Capital Medical University Li Zhenye Capital Medical University Gui Songbai Capital Medical University Zhao Peng Capital Medical University Bai Jiwei Capital Medical University Cao Lei Capital Medical University Cheng Sen Capital Medical University Liu Chunhui Capital Medical University Zhu Haibo Capital Medical University Yazhuo Zhang (  zyz2004520@163.com ) Beijing Neurosurgical Institute https://orcid.org/0000-0002-8583-2580


Introduction
Intracranial epidermoid cysts are congenital, slow-growing and histologically benign tumors, representing about 1% of all intracranial tumors [4,10,7].They are commonly known to arise from misplaced strati ed squamous epithelium during neural tube formation and separation. Epidermoid tumors generally occur in the cerebellopontine angle (CPA) and parasellar regions. They tend to break through the subarachnoid space, and extend into multiple compartments and encase surrounding critical neurovascular structures which make radical surgery di cult to perform.
Traditionally, the epidermoid cysts resection was performed with the aid of an operating microscope.
Later on, the endoscope has been considered to be a more effective tool to improve tumor resection and decrease the incidence of complications for epidermoid cysts [1,15,6,20,19]. Endoscopes have been used as an assisting tool to microscope in resection of epidermoid cysts for the past two decades in our institution. Combined microscopic-endoscopic technique was also used for epidermoid cysts resection in other similar institutions [13,21,16,1,8,14,17]. However, when such technique is used, it is technically infeasible to use microscope and endoscope concurrently, because the speci cations and the size of the microscope does not allow surgeons to use both microscope and endoscope simultaneously [12]. This has limited the application of microscopic-endoscopic technique in epidermoid cysts resection.
In the past ten years, a fully endoscopic technique has also been widely used [4,3,19,6]. When endoscope was used alone, we found it possible that the neurovascular structures cannot be seen through the endoscope when endoscope passes the neurovascular structures. As a result, in fully endoscopic operations, there was a risk of damage to neurovascular structures that were out of the scope of endoscope.
Exoscope has been developed for microneurosurgery which offers quality image and convenient manipulation [9]. Our institution has performed an observational study with combined endoscopic and exoscopic resection of intracranial epidermoid cysts. This article aims at introducing an endoscopicexoscopic technique for the resection of epidermoid cysts. We retrospectively analyzed the patients with intracranial epidermoid cysts who underwent combined endoscopic and exoscopic resection, to explore the bene t of combined endoscopic and exoscopic resection of intracranial epidermoid cysts and evaluated the clinical utility of endoscopic-exoscopic technique.

Patients
Patients with intracranial epidermoid cysts who received whole course combined endoscopic and exoscopic resection between 2017 and 2020 at our institution were analyzed. The diagnosis of epidermoid cysts was con rmed based on MRI information, intraoperative nding and histopathological analysis. Patients' clinical characteristics including demographic data, symptoms, cyst location and surgical information were reviewed. Cyst volume was calculated by the formula V= (A × B × C/2), where A, B, and C represent the maximum diameters of the cyst in each of 3 dimensions[18]. The study protocol was approved by the Ethics Committee of Beijing Tiantan Hospital, and informed consent was obtained from all patients.

Surgical Procedure
Intraoperative neurophysiological monitoring was conducted for safely removing the tumor. After craniotomy, a 90° exoscope (Karl Storz, Tuttlingen, Germany) and a 0°rigid endoscope (Karl Storz, Tuttlingen, Germany) were combinedly used for tumor resection. Both exoscope and endoscope were xed with pneumatic holding arms (Karl Storz, Tuttlingen, Germany) respectively( Figure 1A). The surgical procedures were conducted as follows: rstly, cerebrospinal uid was fully released under exoscope. Subsequently, endoscope was introduced for tumor resection. As the keratin contents continues to be evacuated, endoscope needs to get close to or cross cranial nerve and vascular structures to view the tumors hidden around the corner. At the same time, exoscope was used to see what is around the endoscope. The images of endoscope and exoscope can be displayed on the same screen in parallel or separately ( Figure 1B). Tumor capsule was removed with bimanual technique by sharp dissection. However, if the tumor capsule adhered closely to critical neurovascular structures, the adhesive part of the tumor capsule was left in place. If the scope of 0°rigid endoscope was limited, a 30°rigid endoscope (Karl Storz, Tuttlingen, Germany) was used for further inspecting and resection. After the tumor was removed, multi-angle endoscopic-assisted irrigation was performed to clear the residual irritant contents.

Surgical Outcome Measurements
Surgical Outcome Measurements Total resection was de ned as complete removal of the tumor capsule during surgery and postoperative MRI showed no remnant tumor. Subtotal resection was de ned as incomplete resection of cyst contents (residual cyst content volume ≤10%) and/or residual capsule. Partial resection was de ned as residual cyst content volume >10%. After surgery, outpatient review and MRI scan were conducted at 3, 6 months and then annually.

Statistical Analysis
Statistical analysis was performed using the SPSS v21.0 software (IBM Corp, Armonk, NY, USA). The gross total resection rates within different groups were determined by Fisher exact tests. P<0.05 was considered statistically signi cant.
To explore the factors affecting resection, we analyzed the relevance between total resection rates and the distributions and volumes of cysts. We found that epidermoid cysts spread into the contralateral side was signi cantly associated with nontotal resection(P<0.05) ( Table 2). However, cyst volume and number of areas invaded by the cysts were not associated with total resection rates ( Table 2).

Clinical Outcome And Complications
The clinical symptoms are observed postoperatively. Pain caused by trigeminal neuralgia disappeared in all of the 9 patients. 2 of 3 patients who presented with gait ataxia showed signi cant improvement in their symptoms. Pain relieved in the patient who presented with headache. Hemifacial spasm disappeared for the only patient with the symptom, while the patient's hearing impairment still remained.
No improvement of symptoms was found for the 3 patients with diplopia.
Postoperative surgical complications were seen in 3 patients (3/17, 17.6%), including intracranial infection in 2 patients (2/17, 11.8%), and a delayed postoperative hematoma observed in the seventh day after operation for 1 patient (1/17, 5.9%), who was treated in a conservative manner and recovered smoothly from the hemorrhage.
The median follow-up time was 33.3 months (range 14.5-54.5 months). During the follow-up period, there was no recurrence of the tumors that received total resection. 2 patients developed residual tumor regrowth but did not show any symptom therefore no further surgery was required.

Discussion
The advantages and disadvantages of endoscope It is well known that a complete resection of epidermoid cysts provides a cure for the patients [2] but there are two main di culties when surgeons perform the resection: (1) the cyst wall is very thin and often extends widely into distant corners and cisterns; (2) the wall of epidermoid cysts often adheres to blood vessels and nerves. Both di culties can be effectively solved if there is a way to provide surgeons with a direct visualization of the epidermoid cysts. Operating microscope has been used for epidermoid cysts resection in the past, but the straight-line vision of microscope causes blind areas in the deep structures, the surgeon cannot see into the spaces outside of the view of microscopes, which signi cantly limits the surgeon's ability to perform the total resection of epidermoid cysts. Surgeons need to be able to see into the spaces outside of the view of microscopes during surgery.
Nowadays, it is evident that endoscopes can help nd and resect epidermoid cysts in remote areas that are outside of the scopes of the microscopes, which facilitate maximum epidermoid cysts resection. Coupled with high de nition camera system, endoscopes offer advantage of higher magni cation and wider views. Angled endoscopes permit the surgeon to look around surgical corners, and bimanual operation can be achieved through a xing device. With the recent development of neuroendoscope, whole course neuroendoscopic resection of epidermoid cysts has become feasible. Fully endoscopic surgery for neuroendoscopic resection of epidermoid cysts could decrease traction on the brain, improve total resection rates, and decrease postoperative complications [18,3,19,11]. However, there is one disadvantage in such fully endoscopic surgery. Moving in and out of either side of operation area may result in a collision between the shaft and the neurovascular structures that endoscope is unable to visualize when looking forward at the tumor. Therefore, exoscope has been introduced in association with the endoscopes in order to overcome this limitation.

The Advantages Of Endoscopic-exoscopic Technique
Exoscope works outside of the body cavity and is therefore more similar to the operating microscope than a traditional endoscope. Because exoscope is lighter than microscope, the combination of endoscope and exoscope renders much more convenience during surgery. In the present study, we described our experience with 17 patients who had removal of intracranial tumors with a combined endoscopic and exoscopic approach. The advantages of endoscopic-exoscopic technique can be described as follows: (1) the exoscope can compensate the defect of endoscope's visual eld. (2) because exoscope is lighter than the operating microscope, the combining endoscopic and exoscopic technique provide a higher degree of maneuverability and the exoscope and endoscope can be used concurrently. Considering the lack of stereopsis compared with operating microscope, an initial learning curve period was necessary for neurosurgeons. Based on our study, in spite of the presence of large recurrent epidermoid cysts among all patients and the criteria for the de ning total resection was strict, the total resection rates and postoperative surgical complications of our study were compatible with previous studies [21,5]. Consequently, the endoscopic-exoscopic technique is safe and e cient in the resection of intracranial epidermoid cysts.

Limitations
The ndings of this study have to be seen in light of some limitations. Firstly, the small sample size may introduce some selection bias which may compromise the conclusion drawn from the study. A larger sample size is necessary to accurately evaluate the effectiveness of endoscopic-exoscopic technique. Secondly, there is no certainty that the capsule of giant epidermoid cysts was completely removed, which made it challenging to con rm the total removal of the epidermoid cysts. The third limitation concerns the limited follow-up time. Given a longer follow-up period, the study will generate more accurate conclusions in further study.
In conclusion, endoscopic-exoscopic technique is safe and e cient in the resection of intracranial epidermoid cysts with panoramic views and superior maneuverability. With further development and accumulation of practical experiences, the endoscopic-exoscopic technique can also be applied in the resection of other intracranial tumors.

Declarations
Funding This work was supported by the National Natural Science Foundation of China (82072804).Con icts of interestThe authors declare that they have no con ict of interest.
Availability of data and material The research data is available upon a request.
Code availability Not applicable.
Ethics approval The study protocol was approved by the Ethics Committee of Beijing Tiantan Hospital.
Consent to participate Informed consent was obtained from all patients.
Consent for publication This manuscript is approved by all authors for the submission.

Authors' contributions
Li Chuzhong Conceptualization, methodology, formal analysis, writing-original draft, and writing-review and editing.
Li Zhenye Methodology, acquisition of data, formal analysis, writing-original draft, and writing-review and editing.
Gui Songbai Acquisition of data, supervision and formal analysis. Legend not included with this version Figure 2 Legend not included with this version Page 13/13

Figure 3
Legend not included with this version