How I do it: > 8 Carmustine wafer implantation during supra-marginal resection of a glioblastoma, IDH-wildtype

Abstract

Background

The maximal safe resection of glioblastoma, IDH-wildtype often creates a large resection cavity that can accommodate more than eight Carmustine implants.

Method

We detail the implantation technique of 13 Carmustine wafers within the surgical bed after a right hippocampal formation-sparing anterior temporal lobectomy allowing for the supra-marginal resection of a glioblastoma IDH-wildtype in an adult patient.

Conclusion

Carmustine wafer implantation is a safe and efficient technique following surgical resection of a glioblastoma, IDH-wildtype. Sequential technical steps are required to improve the safety and the efficacy of Carmustine wafer implantation. More than eight Carmustine wafers could be implanted in large surgical cavities with survival benefits for the patients.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00701-025-06675-5.

Relevant surgical anatomyRelevant surgical anatomy

Temporal glioblastoma, IDH-wildtype often presents as large, infiltrative masse that distort the native anatomy of the temporal lobe, complicating surgical orientation and resection planning. In cases where the mesial temporal structures are uninvolved, hippocampal formation preservation may be considered to reduce the risk of postoperative memory impairment, particularly in younger patients or those with dominant hemisphere involvement. The lateral temporal lobe, typically composed of the superior, middle, and inferior temporal gyri, may be significantly displaced or effaced by tumor bulk and associated edema. Key sulcal landmarks such as the Sylvian fissure, collateral sulcus, and parahippocampal gyrus can become difficult to identify intraoperatively, requiring careful correlation with preoperative imaging, intraoperative navigation and ultrasound. Despite anatomical distortion, preservation of the hippocampal formation is still feasible if preoperative imaging demonstrates a clear plane between the tumor and the mesial structures. In such cases, resection involves the temporal pole and lateral neocortex, guided by functional and anatomical boundaries. The posterior extent of the lobectomy must be carefully defined to avoid damage to language-related cortices in the dominant hemisphere. Medially, the hippocampal formation lies beneath the parahippocampal gyrus, adjacent and medial to the temporal horn of the lateral ventricle. When preserved, care must be taken to maintain its vascular supply and anatomical integrity.

Following tumor resection, implantation of biodegradable Carmustine (BCNU) wafers into the resection cavity may be performed to deliver local chemotherapy [1, 5, 10]. Implant placement should avoid direct contact with critical neurovascular structures, such as vascular structures and cerebrospinal fluid (CSF) pathways, to reduce the risk of postoperative toxicity [7]. The irregular shape of the resection cavity requires careful shaping and distribution of the wafers to ensure optimal surface contact without stacking and more than eight wafers can be implanted to cover the whole of the cavity. Moreover, meticulous hemostasis and watertight dural closure are essential to prevent postoperative CSF leakage and wafer migration. Integration of Carmustine wafers into the surgical workflow should be planned preoperatively, considering both the tumor’s anatomical relationships and the feasibility of achieving sufficient resection margins to support local delivery of chemotherapeutic agents.

Description of the technique

Surgical approach

The head is rotated and secured at a 90° angle, positioning the temporal squama in a horizontal plane and aligning the floor of the middle cranial fossa perpendicularly to it (Fig. 1A-B). A reverse question mark–shaped skin incision is made, starting anterior to the tragus and following the superior temporal line (Fig. 1C). The temporal muscle is then reflected anterobasally to the maximum extent to optimize exposure (Fig. 1C).

Fig. 1.

Patient positioning and craniotomy. A The patient is positioned in the supine position with a support placed under the ipsilateral shoulder to facilitate a monoaxial rotation of the torso. This setup minimizes excessive head rotation, thereby reducing the risk of internal jugular vein compression. B The head is rotated and secured at a 90° angle, positioning the temporal squama in a horizontal plane and aligning the floor of the middle cranial fossa perpendicularly to it. C A curvilinear “question mark”–shaped skin incision is made, starting from the tragus and extending anteriorly into the frontal region, following the superior temporal line. The incision is placed just beyond the hairline to minimize visible scarring and reduce aesthetic impact. D The temporal craniotomy is centered below the squamous suture to ensure optimal exposure of the superior (T1), middle (T2), and inferior (T3) temporal gyri

A temporal craniotomy is performed, with its superior margin positioned slightly above the squamous suture—approximately 0.5 cm above the Sylvian fissure (Fig. 1D). Then, we extended the craniotomy anteriorly using bone forceps from the temporal bone to the zygoma to allow the entire temporal pole to be exposed. Upon opening the dura, the Sylvian fissure, as well as the superior (T1), middle (T2), and inferior (T3) temporal gyri, should be clearly exposed (Fig. 1D).

Right temporal glioblastoma en-bloc resection

The posterior extent of the anterior temporal lobectomy is marked by coagulation of the pia mater. Particular care is taken to preserve the draining vein of the Sylvian fissure, which may be displaced or stretched by the tumor mass (Fig. 2a-b). Penetration of the pia mater with one branch of the bipolar forceps ensures thorough coagulation of the pia mater and its vascular contents. Pial coagulation over T1 is performed parallel to the Sylvian fissure, maintaining a safety margin of several millimeters to avoid inadvertent injury and subarachnoid bleeding from small arteries supplying adjacent extratemporal structures, which may be more vulnerable due to distortion by the tumor (Fig. 2c-d). The coagulated pia mater is then sharply incised with microscissors. Resection of the lateral neocortical block follows, using ultrasonic aspiration. The tumor mass often alters cortical architecture, but anatomical orientation is restored by identifying first the anterior part of the temporal horn of the lateral ventricle. At the posterior resection limit, the temporal horn is opened in a coronal plane, defining the medial boundary of this surgical step. Even a small CSF outflow confirms successful ventricular entry, serving as a key intraoperative landmark. Once the temporal horn is identified, ultrasonic aspiration is directed anteriorly along T1 toward the temporal pole, following the Sylvian fissure. Posterior resection is then extended basally toward the floor of the middle cranial fossa. The pia mater is coagulated and incised, releasing the posteroinferior portion of the neocortical block. Aspiration continues along the temporal horn, reaching the basal and polar arachnoid, which is carefully opened to allow en bloc removal of the lateral neocortical component of the tumor-bearing temporal lobe.

Fig. 2.

Surgical technique of anterior temporal lobectomy step-by-step. a, b Following elevation of the temporalis muscle and dural opening, the inferior frontal gyrus of the frontal lobe (F), Sylvian fissure (SF), and the superior, middle, and inferior temporal gyri of temporal lobe (T) are exposed; c, d coagulation of the arachnoid plane is performed, followed by progressive subarachnoid dissection of the temporal gyri using bipolar forceps. This dissection is carried out approximately 2.5 cm from the tip of the temporal pole on the left side and up to 3 cm on the right side to avoid damage to neurofunctional connectivity; e, f anteriorly, the subarachnoid dissection of the temporal uncus enables safe identification of the internal carotid artery (ICA) and the third cranial nerve (III); g, h The temporal resection is extended inferiorly toward the floor of the cranial temporal fossa (TF), allowing exposure of the free edge of the tentorium (Te) and, posteromedially, the temporal horn of the lateral ventricle (Th). F: frontal lobe, ICA: internal carotid artery, III: third cranial nerve, SF: Sylvian Fissure, T: temporal lobe, Te: tentorium (Te), TF: temporal fossa, Th: temporal horn of the lateral ventricle

The following anatomical landmarks assist in orientation during the resection of a temporal glioblastoma: the hippocampal formation, ependyma, and choroid plexus of the temporal horn, the choroidal fissure, and the collateral eminence (Fig. 2e-f). The glioblastoma, which often infiltrates the surrounding structures, can distort these landmarks, making identification challenging but essential. The uncus, which contains the amygdalar nuclei and the head of the hippocampal formation, protrudes into the ventricle anteriorly and superiorly to the choroidal point. It can be displaced and herniated towards the tentorial notch and can be difficult to distinguish due to tumor involvement, is the structure. To release masse effect and herniation, uncus is carefully resected subpially using ultrasonic aspiration to minimize damage to adjacent structures. At this step, the pia mater is the only structure that prevent damaging internal carotid artery, posterior cerebral artery, anterior choroid artery, third cranial nerves, and cerebral peduncle that are visible through pial mater (Fig. 2e-f). The resection of parahippocampal structures (parahippocampal and fusiform gyri) and temporo-basal cortex can be guided by the intraventricular identification of the collateral eminence, which is lateral and parallel to the hippocampal formation. The ultrasonic aspiration towards the collateral eminence down to the tentorium and middle skull base allows joining the collateral sulcus (Fig. 2g-h).

Carmustine wafer implantation

After achieving maximal safe resection of the glioblastoma, IDH-wildtype, careful haemostasis with cotonoid dabbing is performed to ensure a dry surgical field without interposition of any layer of cellulose hemostat (Video 1). Carmustine wafers, previously kept at the recommended temperature, are opened right at the time of implantation. After gloves change, they are manipulated in a surgical tray with tools dedicated to Carmustine wafer implantation. They are implanted directly onto the walls of the resection cavity, without any interposing material. The wafers are secured using a large layer of absorbable cellulose hemostat, and then covered with biological glue (2cm³ at least). Finally, a watertight dural closure covered by absorbable cellulose hemostat and biological glue (2cm³ at least) is performed to prevent CSF leakage and minimize the risk of postoperative complications.

Indications [3, 7]

Treatment of newly diagnosed [10] and suspected glioblastoma, IDH-wildtype when a subtotal, total or supratotal resection of the contrast enhancement appears achievable.

• highly recommended for “glioblastoma-like” gliomas with ring-like contrast enhancement and necrosis on preoperative MRI;

• not recommended for non-enhancing and non-necrotic diffuse glioma on MRI;

• to be discussed for other cases.

Treatment of recurrent [1] glioblastomas, IDH-wildtype in whom a subtotal, total or supratotal resection of the contrast enhancement appears achievable:

• highly recommended for MGMT-methylated glioblastomas, IDH-wildtype [4];

• to be discussed for MGMT-unmethylated glioblastomas, IDH-wildtype.

Carmustine wafer implantation is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50 [6].

The number of Carmustine wafers should be adapted to the size of the resection cavity to improve survival without increasing postoperative overall complication rates. Up to 24 implanted wafers have been reported to be safe [6].

Limitations

Main contraindications are:

• Lack of preoperative informed consent by the patient;

• Partial surgical resection (i.e. < 90% of the contrast enhancement) expected based on preoperative brain MRI;

• Intraoperative frozen section diagnosis of a tumor other than a high-grade glioma;

• Expected difficulties in achieving a watertight dural closure;

• Known allergy to Carmustine;

How to avoid complications [7]

• Ventricular opening is not considered a contraindication. However, in cases of extensive opening, the risk of obstructive hydrocephalus should be carefully considered and controlled by ventricle closing with layers of cellulose absorbable hemostat followed by the application of biological glue.

• In cases of Carmustine wafer migration without hydrocephalus, we suggest considering a conservative medical treatment with close clinic-radiological monitoring. In cases of Carmustine wafer migration associated with obstructive hydrocephalus, we suggest to perform a new surgical procedure to treat the hydrocephalus and remove all the wafers.

• Carmustine wafers should be handled and stored at the recommended temperature as per the manufacturer's guidelines, with the package being opened only immediately prior to implantation.

• Haemostasis must be performed prior Carmustine wafer implantation to avoid interposition of blood between the wafers and the brain parenchyma.

• Implant the Carmustine wafer directly onto the surgical bed without interposing cellulose absorbable hemostat between the wafer and the tissue.

• Carmustine wafers can be stabilized and secured using biological glue and cellulose absorbable hemostat to ensure proper adhesion.

• Watertight dural closure is essential to minimize the risk of cerebrospinal fluid leaks and to reduce the potential for postoperative wound defects and infection.

• If a perfect seal is not achieved, dural closure can be obtained through duraplasty, using primarily autologous pericranium or synthetic dura mater as a graft.

• A dedicated postoperative systemic corticosteroid therapy should be initiated and maintained to reduce inflammation and support recovery.

Specific perioperative considerations

• Informed consent before surgery is mandatory.

• Extent of surgical resection assessment based on preoperative brain MRI.

• MGMT promoter methylation status available for recurrent glioblastomas, IDH-wildtype.

Specific information for the patient

• Informed consent of the patient before surgery is mandatory.

• Intraoperative frozen section diagnosis of a high-grade glioma allows Carmustine wafer implantation.

• Clinical trials [1, 10] demonstrated a survival benefit of the Carmustine wafer implantation in high-grade glioma patients but before the Stupp era.

• Most of the cohort studies [2, 5, 8] showed a survival benefit of the Carmustine wafer implantation in glioblastomas, IDH-wildtype after the Stupp era.

• Carmustine wafer implantation is associated with potential risks, including surgical site infection and reoperation.

• The benefit-risk ratio allows Carmustine wafer implantation [3, 7].

• Serial changes on postoperative brain MRI are induced by Carmustine wafer implantation [9] and benign surgical bed cyst occurs approximatively in 18% of cases.

Key points summary

• Carmustine wafer implantation is an optional treatment for glioblastoma, IDH-wildtype which is more efficient for MGMT-methylated tumors

• Carmustine wafers must be implanted one by one after a complete hemostasis without superposition, and then stabilized

• Carmustine wafers must be implanted one by one after a complete hemostasis without superposition, and then stabilized

• We suggest to cover all the brain parenchyma with Carmustine wafers in order to improve survival. Based on our experience, up to 24 Carmustine wafers can be safely implanted within the surgical cavity.

• Carmustine wafer implantation is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50 with the same indications, intraoperative administration technique, and peri-operative protocols.

• A dedicated implantation sequential protocol must be respected to prevent postoperative complications

• In our experience, large ventricular opening is not a contraindication of Carmustine wafer implantation but we recommend a ventricle closing technique in order to prevent post-operative hydrocephalus.

• A dedicated postoperative systemic corticosteroid therapy should be initiated and maintained until radiotherapy after Carmustine wafer implantation

• Serial changes on postoperative MRI follow-up are induced by Carmustine wafer implantation and benign surgical bed cyst occurs in about 20% of cases, which could be manage conservatively in all cases.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contribution

Alexandre ROUX, Conception and design of the study, Acquisition and analysis of data, Performed surgical procedure, Drafting a significant portion of the manuscript, figures and video.Angela ELIA, Acquisition and analysis of data, Drafting a significant portion of the manuscript, figures and video.Marc ZANELLO, Acquisition and analysis of data, Drafting a significant portion of the manuscript, figures and video.Johan PALLUD, Conception and design of the study, Acquisition and analysis of data, Drafting a significant portion of the manuscript, figures and video.

Funding

None.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Ethical Approval

The requirement to obtain informed consent was waived according to French legislation.

Competing interests

The authors declare no competing interests.

Disclosure

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Alexandre ROUX, Angela ELIA, Marc ZANELLO, and Johan PALLUD have received honoraria for consultancy from Kyowa Hakko Kirin Co. Alexandre ROUX and Johan PALLUD have received honoraria for speaking engagements (including travel and accommodation) from Kyowa Hakko Kirin Co.