Endoscopic Third Ventriculostomy and Pineal Biopsy from a Single Entry Point

Abstract

Pineal neoplasms have a significant impact on children although they are relatively uncommon. They account for approximately 3-11% of all childhood brain tumors, which is considerably higher than the <1% seen in adult brain tumors. These tumors can be divided into three main categories: germ cell tumors, parenchymal pineal tumors, and tumors arising from related anatomical structures. Obtaining an accurate and minimally invasive tissue diagnosis is crucial for selecting the most appropriate treatment regimen for patients with pineal gland tumors. This is due to the diverse treatment options available and the potential risks associated with complete resection. In cases where patients present with acute obstructive hydrocephalus caused by a pineal gland tumor, immediate treatment of the hydrocephalus is necessary. The urgency stems from the potential complications of hydrocephalus, including increased intracranial pressure and neurological deficits. To address these challenges, a minimally invasive endoscopic approach provides a valuable opportunity. This technique allows clinicians to promptly relieve hydrocephalus and obtain a histological diagnosis simultaneously. This dual benefit enables a more comprehensive understanding of the tumor and assists in determining the most effective treatment strategy for the patient.

Introduction

The pineal gland is a neuroendocrine gland located in the epithalamus that is responsible for regulating biological rhythms in vertebrates. Its anatomical boundaries include the posterior surface of the wall of the third ventricle, which forms the base of the gland, the splenium of the corpus callosum superiorly, and the thalamus surrounding both sides. It has a pinecone shape and extends posteriorly and inferiorly in the quadrigeminal cistern^1,2.

Pineal neoplasms are relatively rare tumors and are predominantly childhood malignancies, accounting for 3-11% of all childhood brain tumors compared with <1% of adult brain tumors^1,3,4. Age, sex, and ethnicity can modify the relative incidence of pineal neoplasms⁵. Pineal tumors are classified into three types: germ cell tumors, pineal parenchymal tumors, and tumors arising from neighboring anatomical regions. Germinomas are the most frequent pineal tumors, accounting for up to 50% of pineal tumors in Europe^1,3.

Tumors of the pineal gland are pathologically diverse and their optimal management remains controversial⁶. Advances in neuroendoscopy have significantly contributed to treating pineal region tumors. Neuroendoscopic techniques are minimally invasive, effective, and safe in treating these tumors. With this technique, it is possible to treat hydrocephalus and obtain a biopsy simultaneously⁷. In most cases, simultaneous endoscopic third ventriculostomy (ETV) and tumor biopsy is the first-choice surgical procedure for pineal region tumors due to the effectiveness of radiotherapy and chemotherapy in most histopathological subtypes. Various techniques for simultaneous ETV and biopsy have been described, and there is currently no standard technique for performing this procedure⁸.

Protocol

The Institutional Review Committee of the Istanbul Faculty of Medicine approved the study protocol. Before the start of the study, the patient was asked to sign an informed consent form outlining the purpose of use and publication of their data.

1. Preoperative procedures

1. Perform the operations under general anesthesia. Prepare endoscopic and optical equipment in the operating room.
2. Check the instruments before starting the procedure (Figure 1 and Table 1).

2. Surgical technique (Figure 2)

1. Place the patient in the supine position under general anesthesia. Support the patient's head with a soft head support and bend it at a 10° angle.
2. Palpate the coronal suture. The Kocher point is just anterior to the coronal suture and approximately 2.5 cm to the right of the midline.
3. Begin the operation by following routine asepsis and antiseptic rules.
   1. Make a 5 cm curvilinear incision in the right frontal region, including Kocher's point, using a #20 blade.
   2. Ensure hemostasis with bipolar cautery and dissect the skin and subcutaneous tissue.
   3. Place the automated skin retractor.
   4. Scrape the periosteum using an Adson periosteal elevator.
   5. Drill a burr hole in the anterior region using a high-speed drill and perforator.
   6. Open the dura in a cruciform shape with a #11 blade and coagulate the underlying pia with bipolar cautery.
   7. Insert the endoscope sheath into the brain parenchyma perpendicular to the burr hole and remove the obturator while holding the endoscope sheath. After entering the lateral ventricle, cerebrospinal fluid is seen to exit the endoscope sheath.
      NOTE: The examination of tumor markers such as alpha-feto-protein and B-Hcg in the cerebrospinal fluid (CSF) sample increases the accuracy of the histological examination.
   8. Insert the 6.1 mm wide endoscope into the endoscope sheath. Visualize the lateral ventricular cavity.
      1. Identify the septal and thalamostriate veins in the lateral ventricle.
      2. Identify the choroid plexus. Follow the choroid plexus anteriorly up to the third ventricle going through the Foramen of Monro (FOM).
   9. Pass the ventriculoscope through the FOM to access the third ventricle.
   10. Find the floor of the third ventricle, which is usually thin due to hydrocephalus.
       1. Identify the mammillary bodies and infundibular recess in the third ventricle.
       2. Ensure that the hole at the base of the third ventricle is located at the most translucent point between the infundibular recess and the mammillary bodies.
   11. Locate the basilar artery and puncture anterior to the arterial complex to prevent damage and hemorrhage during surgery.
   12. Use the tip of the 4F Fogarty catheter to puncture the base of the third ventricle. Then, repeatedly inflate and deflate the balloon of the catheter to widen the opening. See the jet flow of cerebrospinal fluid when the catheter balloon is deflated.
   13. If bleeding occurs during surgery, irrigate with copious amounts of warm fluid until all bleeding has visibly stopped and CSF has cleared.
       NOTE: There are different opinions in the literature about the fluids used to manage bleeding. However, we use Ringer's lactate solution at normal body temperature in our clinic.
   14. Move the endoscope to the posterior region of the third ventricle where the pineal gland tumor is located.
       NOTE: The entry point and angle of the endoscope play a pivotal role in accessing these two structures, which are positioned at different locations. This is essential to avoid damage to the fornix and critical vascular structures.
   15. Identify the massa intermedia and perform dissection to allow better visualization of the posterior third ventricle.
   16. Identify the tumor and examine the growth pattern. Carefully coagulate the surface of the tumor using bipolar cautery.
   17. After complete coagulation of the tumor surface, take a biopsy using biopsy forceps. Send the biopsy to the pathology unit for frozen analysis and resect the tumor according to the histopathological diagnosis.
   18. Control local hemorrhage with irrigation and bipolar cautery.
   19. Remove the Endoscopic System.
   20. Close the wound with sutures without a drain.

3. Postoperative procedures

1. The hospital stay is minimal. Mobilize the patient on the second day following surgery.
2. Perform non-contrast cranial CT and CSF flow MRI to evaluate the patency of the third ventriculostomy and exclude the presence of bleeding.
3. Discharge patients the following day if there are no complaints.
4. Ask the patients to follow the pathology results and attend the outpatient clinic on the tenth day and at the end of the first month.

Representative Results

Preoperative magnetic resonance imaging (MRI) revealed a pineal tumor and triventricular hydrocephalus. Before the surgery, we ensured that our endoscope set, 4F Fogarty balloon catheter (see Figure 1), and all required materials (see Table 1) were checked. The size of the pineal tumor was initially measured at 30 mm x 15 mm x 20 mm. However, on postoperative MRI scans, it was observed that the tumor had increased in size to 35 mm x 52 mm x 45 mm, suggesting a progressive nature of the tumor. Fortunately, after undergoing chemotherapy, there was a positive response to treatment. The tumor size was significantly reduced to 15 mm x 15 mm x 10 mm, indicating a successful outcome.

Additionally, the contrast uptake was also significantly reduced, further supporting the effectiveness of the chemotherapy treatment. Figure 3 provides a visual representation of the reduction in tumor size and hydrocephalus throughout the treatment period. This graphical representation highlights the positive progress made in managing both the tumor and hydrocephalus. During the surgical procedure, continuous irrigation was employed, making it difficult to accurately measure the amount of blood loss. However, it is worth noting that no intraoperative transfusion was required for this patient, indicating that the blood loss was not significant.

Furthermore, there was no significant decrease in hemoglobin levels after the surgery, suggesting that the patient's blood levels remained stable throughout the procedure. Overall, the combination of chemotherapy and surgical intervention has proven to be effective in reducing the size of the pineal tumor and managing the triventricular hydrocephalus. The positive response to treatment is evident in the reduction of tumor size and contrast uptake, providing hope for the patient's recovery.

Figure 1: Karl-Storz endoscope set and 4F Fogarty balloon catheter. 1: Biopsy Forceps; 2: Endoscope sheath; 3: Obturator; 4: Ventriculoscope; 5: Bipolar coagulation electrode; 6: 4F Balloon catheter. Please click here to view a larger version of this figure.

Figure 2: A schematic illustration of endoscopic third ventriculostomy and pineal biopsy with a rigid endoscope, utilizing Kocher's point. Please click here to view a larger version of this figure.

Figure 3: A magnetic resonance imaging scan performed on a patient with a pineal gland tumor and triventricular hydrocephalus. (A) Preoperative contrast-enhanced T1 sequence sagittal; (B) preoperative contrast-enhanced T1 sequence axial; (C) preoperative T2 sequence sagittal; (D) preoperative T2 sequence axial. (E) Contrast-enhanced T1-sequence sagittal MRI before chemotherapy and 1 month after surgery; (F) contrast-enhanced T1-sequence axial MRI before chemotherapy and 1 month after surgery.(G) T2 sequence sagittal MRI before chemotherapy and 1 month after surgery; (H) T2 sequence axial MRI before chemotherapy and 1 month after surgery. (I) Contrast-enhanced T1-sequence sagittal MRI at the second month after chemotherapy; (J) Contrast-enhanced T1-sequence axial MRI at the second month after chemotherapy and axial.(K) T2 sequence sagittal MRI at the second month after chemotherapy and axial; (L) T2 sequence axial MRI at the second month after chemotherapy. Please click here to view a larger version of this figure.

Discussion

The description of the ETV and biopsy for pineal tumors was first described in the 1970s. Historically, the fear of uncontrolled hemorrhage has always existed. However, owing to advances in endoscopic surgery techniques, bleeding control is not a major complication for experienced surgeons nowawadays^9,10. According to several cases in the literature, endoscopic management has been found to be effective as an initial step for pineal region tumors presenting with hydrocephalus. The primary aims of endoscopic management are both CSF drainage and tissue diagnosis for further management⁸.

Pineal tumors are a diverse group of tumors with different histological characteristics. The tumors can be classified into four main groups: germ cell tumors, tumors of pineal origin, tumors of neuroepithelial origin, and a variety of other tumors, including metastases. Considering the wide range of treatment options available for these tumors and the potential risks associated with complete resection, it is important to diagnose the tumor accurately at the time of diagnosis using minimally invasive tissue sampling. Patients presenting with acute hydrocephalus secondary to pineal gland tumors require immediate treatment of the hydrocephalus and minimally invasive endoscopic surgery offers the opportunity to simultaneously diagnose the histology^1,7.

ETV with simultaneous biopsy of a pineal gland lesion has been adopted as a management strategy for these rare tumors^6,11,12,13. This approach has several advantages, including biopsy sampling in addition to CSF drainage, CSF sampling for the study of tumor markers such as alpha-fetoprotein and human chorionic gonadotropin, and the ability to minimize bleeding from the rich vascular tissue under direct visualisation^7,14,15. The tumor types in this region exhibit a wide range of diversity, and within each tumor, there may be heterogeneity, such as teratoma, pineocytoma, and glioma. Therefore, to determine a formal treatment strategy, an accurate diagnosis is essential^1,6,16.

The two most common intraoperative complications during endoscopic pineal region biopsy are intraventricular hemorrhage due to venous bleeding and iatrogenic contusion of the fornix due to rigid endoscope use in patients with narrow foramen Monro¹⁷. The incidence of these complications decreases significantly with increasing experience in endoscopic surgery, preoperative planning, and appropriate patient selection. When a single access site is used for ETV and pineal biopsy, the use of a ventriculoscope with a 30° angled lens provides a wider field of view and less fornix ecartation, resulting in fewer complications¹⁸.

There is no consensus on the optimal approach to performing ETV before tumor biopsy in a single-port procedure. The rationale for choosing ventriculostomy as the first step is that the potential for visual blurring may complicate ETV due to the risk of tumor hemorrhage after biopsy. In patients with critically high intracranial pressure and obstructive hydrocephalus, treatment of hydrocephalus should be prioritized¹⁷.

Various techniques such as ETV and ventriculoperitoneal shunt placement have been used in the treatment of obstructive hydrocephalus associated with pineal region tumors¹⁹. Many patients may not need CSF diversion after the lesion is removed or reduced in size with chemotherapy and radiotherapy²⁰. For obstructive hydrocephalus associated with lesions in the pineal region, ETV is a widely used minimally invasive technique. Furthermore, tumor biopsies obtained with ETV, especially those used to diagnose germ cell tumors, may avoid surgical resection due to their high radiosensitivity²¹.

Endoscopic biopsy and third ventriculostomy can be performed with both rigid and flexible endoscopes in a single session using the monoportal technique¹¹. However, the inferior optical quality of the flexible endoscopic system has become a significant limitation, potentially hindering the ability to detect tumor spread²². In addition, the smaller size of the flexible forceps compared to the rigid endoscope forceps may affect the size of the biopsy sample, resulting in inconsistent histology results¹⁰. Moreover, it may be difficult to maneuver the flexible ventriculoscope through the Foramen of Monro and toward the massa intermedia of the third ventricle. Furthermore, the tumor should be biopsied and coagulated without irrigation. More importantly, a lot of bleeding from the biopsy site could lead to total loss of vision^10,11.

In conclusion, treatment regimens for these tumors vary. Complete resection carries a high risk of morbidity and mortality due to its close location to important anatomical structures. In cases where patients present with acute obstructive hydrocephalus caused by a pineal gland tumor, it is imperative to treat the hydrocephalus promptly. The endoscopic approach provides the possibility of simultaneous histological diagnosis²³.

Materials

Name	Company	Catalog Number	Comments
Adson periosteal elevator	Ruggles-Redmond	RO263	Semi-sharp, 5 mm, curved 6-3/8, length 164 mm
Automatic skin retractors	Integra	3,72,245	Heiss Automatic Skin Retractor Length - Overall (mm): 102 Length 1 - Tip/Jaw (mm): 8
Balloon catheter	Edwards Fogarty	120804FP	Length (cm): 80, Catheter size (F): 4,  Inflated balloon diameter (mm): 9
Biopsy Forceps	Karl Storz LOTTA CLICKLINE Grasping Forceps	28164 LE	Rotating, dismantling, single action jaws, diameter 2.7 mm, working length 30 cm
Bipolar coagulation electrode	Karl Storz LOTTA	28161 SF	Diameter 1.3 mm, working length 30 cm
Bisture	Beybi	24,02,502	Beybi Bisture Tip. No: 20 and No: 11
High-speed drill	Medtronic Midas Rex MR8	MR8™ Electric Plus EM850	Perforator tip used
Obturator	Karl Storz LOTTA	28164 LLO	Use with Operating Sheaths for ventricular puncture
Operating sheath	Karl Storz LOTTA	28164 LSB	Graduated, rotating, outer diameter 6.8 mm, working length 13 cm
Ventriculoscope	Karl Storz LOTTA Ventriculoscope with HOPKINS	28164 LAB	Wide angle telescope 30°, angled eyepiece, outer diameter 6.1 mm, length 18 cm, working channel diameter 2.9 mm, irrigation/suction channel diameter 1.6 mm