Photodynamic therapy using talaporfin sodium for non-totally resectable malignant glioma.

BACKGROUND: For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma. METHODS: Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery. RESULTS: In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months. CONCLUSIONS: PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions.

Efficacy of interstitial photodynamic therapy using talaporfin sodium and a semiconductor laser for a mouse allograft glioma model.

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.

A Cerebral Embolism Caused by a Malignant Peripheral Nerve Sheath Tumor in a Patient with Neurofibromatosis Type 1.

A 31-year-old man with neurofibromatosis type 1 (NF-1) had undergone resection of a malignant peripheral nerve sheath tumor (MPNST) on the buttock 3 months previously. He subsequently underwent mechanical thrombectomy for a hyperacute left middle cerebral artery embolism. Histopathologically, the emboli comprised neurofilament-positive pleomorphic tumor cells with geographic necrosis and conspicuous mitosis and were identified as MPNST. The patient died of respiratory failure due to lung MPNST metastasis on day 15 of hospitalization. To our knowledge, this is the first report of a spontaneous cerebral embolism due to MPNST in a NF-1 patient.

Pathology for severe inflammatory PML with PD1/PD-L1 expression of favorable prognosis: What's a prognostic factor for PML-IRIS?

A 72-year-old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1-hypointense area. Multiple T2/FLAIR-hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high-dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR-hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+ /CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti-viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD-1 and PD-L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD-1/PD-L1 immune-checkpoint regulation.

Patient with Diffuse Midline Glioma, H3 K27-altered, Carrying an FGFR1 Mutation Who Experienced Thalamic Hemorrhage: A Case Report and Literature Review.

Diffuse midline glioma (DMG), H3 K27M-altered, is a tumor with a poor prognosis mainly found in children. An adolescent patient presented with thalamic hemorrhage, which initially could not be diagnosed as DMG by pathological analysis. A neoplasm in the lateral ventricle close to the previous thalamic hemorrhagic lesion was detected 12 months after the hemorrhage. Thus, endoscopic resection was performed, and a diagnosis was made. Gene expression profiling demonstrated mutation in genes, such as H3F3A and FGFR1. FGFR1 mutation was associated with intratumoral hemorrhage in low-grade gliomas and contributed to longer survival than wild-type FGFR1 in DMG H3K27M. Our findings suggest that patients with DMG, H3 K27-altered, with FGFR1 mutation may be predisposed to intratumoral hemorrhaging and/or have a longer survival time than patients without FGFR1 mutation.

Trigeminal Schwannoma Surgery: Challenges in Preserving Facial Sensation.

Treatments of schwannoma have dramatically improved in the previous few decades, but preservation of the functions of the originating nerve, such as facial sensation in trigeminal schwannomas, still remains challenging. As the preservation of facial sensation in trigeminal schwannomas has not been analyzed in detail, we here review our surgical experience of more than 50 trigeminal schwannoma patients, particularly focusing on their facial sensation. Since the facial sensation in each trigeminal division showed a different perioperative course even in a single patient, we investigated patient-based outcomes (average of the three divisions in each patient) and division-based outcomes separately. In the evaluation of patient-based outcomes, facial sensation remained postoperatively in 96% of all the patients, and improved in 26% and worsened in 42% of patients with preoperative hypesthesia. Posterior fossa tumors tended to most rarely disrupt facial sensation preoperatively, but were the most difficult to preserve facial sensation postoperatively. Facial pain was relieved in all six patients with preoperative neuralgia. In the division-based evaluation, facial sensation remained postoperatively in 83% of all the trigeminal divisions, and improved in 41% and worsened in 24% of the divisions with preoperative hypesthesia. The V3 region was most favorable before and after surgery, with the most frequent improvement and the least frequent functional loss. To clarify current treatment outcomes of the facial sensation and to achieve more effective preservation, standardized assessment methods of perioperative facial sensation may be required. We also introduce detailed MRI investigation methods for schwannoma, including contrast-enhanced heavily T2-weighted (CISS) imaging, arterial spin labeling (ASL), and susceptibility-weighted imaging (SWI), preoperative embolization for rare vascular-rich tumors, and modified techniques of the transpetrosal approach.

[Intraoperative Neuromonitoring in Vestibular Schwannoma Surgery].

Vestibular schwannoma surgery necessitates intraoperative neuromonitoring to secure long-term tumor control by sufficient tumor removal and preservation of neural function. Therein, facial nerve function can be assessed in real-time and quantitatively by intraoperative continuous facial nerve monitoring with repetitive direct stimulation. The ABR and, further, CNAP, are closely monitored for the continuous assessment of the hearing function. In addition, the evoked masseter and extraocular electromyograms, SEP, MEP, and neuromonitoring of the lower cranial nerves are implemented as needed. In this article, we introduce our neuromonitoring techniques during vestibular schwannoma surgery with an illustrative video.

First Clinical Report of the Intraoperative Macro- and Micro-Photodiagnosis and Photodynamic Therapy Using Talaporfin Sodium for a Patient with Disseminated Lumbar Medulloblastoma.

Photodiagnosis (PD) and photodynamic therapy (PDT) using the second-generation photosensitizer talaporfin sodium together with an exciting laser for primary intracranial malignant tumors is well recognized in Japan, and many medical institutions are introducing this new therapeutic option. In particular, intraoperative PDT using talaporfin sodium for infiltrating tumor cells in the cavity walls after the resection of malignant glioma is now covered by health insurance after receiving governmental approvement, and this method has been recommended in therapeutic guidelines for primary malignant brain tumors in Japan. On the other hand, experimental and clinical studies on the development of novel therapeutic strategies for malignant spinal cord tumors have not been reported to date, although their histological features are almost identical to those of intracranial malignant tumors. Therefore, the clinical outcomes of malignant spinal cord tumors have been less favorable than those of malignant brain tumors. In this report, we performed the PD and PDT using talaporfin sodium on a patient with a metastatic lumbar lesion that was detected on magnetic resonance image (MRI) 50 months after the resection of cerebellar medulloblastoma who presented with lumbago and sciatica. We were able to detect the target lesion in the conus medullaris using a surgical microscope, and detected the disseminated medulloblastoma cells floating in the cerebrospinal fluid using a compact fluorescence microscope. Furthermore, we performed PDT to the resected lumbar lesion with the adjuvant platinum-based chemotherapy, and the patient survived a meaningful life for more than 2 years after the lumbar surgery. This report describes the first case of a human patient in whom the efficacy of PD and PDT was demonstrated for a malignant spinal cord tumor.

Features of postoperative hearing function changes in patients with cerebellopontine angle and intratemporal tumors other than vestibular schwannomas.

OBJECTIVE: Tumors around the cerebellopontine angle (CPA) and temporal bone can potentially affect hearing function. In patients with such tumors other than vestibular schwannomas (VSs), auditory tests were investigated before and after surgery to characterize the auditory effect of each tumor and to determine prognostic factors. METHODS: A total of 378 patients were retrospectively evaluated for hearing functions before and after surgery. These 378 patients included 168 with CPA meningioma, 40 with trigeminal schwannoma (TS), 55 with facial nerve schwannoma (FNS), 64 with jugular foramen schwannoma (JFS), and 51 with CPA epidermoid cyst (EPD). RESULTS: Preoperative hearing loss was observed in 124 (33%) of the 378 patients. Of these 124 patients, 38 (31%) experienced postoperative hearing improvement. Postoperative hearing deterioration occurred in 67 (18%) of the 378 patients. The prognostic factors for postoperative hearing improvement were younger age and the retrocochlear type of preoperative hearing disturbance. Tumor extension into the internal auditory canal was correlated with preoperative hearing loss and postoperative hearing deterioration. Preoperative hearing loss was observed in patients with FNS (51%), JFS (42%), and MGM (37%), and postoperative hearing improvement was observed in patients with JFS (41%), MGM (31%), and FNS (21%). Postoperative hearing deterioration was observed in patients with FNS (27%), MGM (23%), and EPD (16%). CONCLUSIONS: According to the results of this study in patients with CPA and intratemporal tumors other than VS, preoperative retrocochlear hearing disturbance was found to be a prognostic factor for hearing improvement after surgery. Among the tumor types, JFS and MGM had a particularly favorable hearing prognosis. The translabyrinthine approach and cochlear nerve section should be avoided for these tumors, regardless of the patient's preoperative hearing level.

A Case of Primary Central Nervous System Lymphoma That Developed in a Patient Receiving Fingolimod Therapy for Multiple Sclerosis.

Fingolimod is an oral medication for the prevention of multiple sclerosis relapse, and its efficacy has been demonstrated in several clinical trials. Fingolimod has various side effects, such as arrhythmia and hepatic dysfunction. In addition, there have been rare reports of the development of lymphoproliferative disorders in patients undergoing fingolimod therapy, including primary central nervous system lymphoma (PCNSL). We diagnosed and treated a multiple sclerosis patient who developed PCNSL while undergoing fingolimod therapy. Fourteen months after starting fingolimod therapy, the patient developed aphasia, and underwent biopsy analysis for a lesion displaying a homogeneous gadolinium-enhanced lesion in the left frontal lobe. The lesion was diagnosed as diffuse large B-cell lymphoma by pathological examination. After the diagnosis, the patient received chemotherapy together with methotrexate combination therapy, and the lesion became smaller and the patient's symptoms improved. Although several autopsy cases of PCNSL in patients who received fingolimod therapy have been reported, there have been few reports to date of patients diagnosed by biopsy analysis.

Resection of petroclival clear cell meningioma by the anterior transpetrosal approach: diagnosis of rare pathology and improvement of preoperative hearing disturbance.

Clear cell meningioma is a rare histological variant of meningioma, which often recurs aggressively. This video demonstrates a patient with a petroclival clear cell meningioma, which was resected completely through the anterior transpetrosal approach. The absence of intratumoral spotty signal voids on preoperative susceptibility-weighted imaging (SWI) suggested that the tumor was a meningioma rather than a schwannoma, although typical imaging features of meningioma were not observed. After surgery, the patient's preoperative hearing disturbance improved from class D to class A, which the authors had sometimes experienced in cerebellopontine angle meningioma surgeries. Careful observation over a 2.5-year period revealed no tumor recurrence, without additional treatment. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21219.

[Lateral Suboccipital Retrosigmoid and Far Lateral Approaches:Various Extensions for Schwannoma, Meningioma, and Epidermoid Cyst Surgery].

The lateral suboccipital retrosigmoid approach is one of the most established approaches for accessing the posterior cranial fossa. In order to expand the surgical field, several extensions, including(1)extended craniotomy(e.g., far lateral, transcondylar, and transsigmoid approaches), (2)additional intradural osseous or bony drilling(e.g., transmeatal and suprajugular approaches), and (3)fissure dissection(e.g., suprafloccular and infrafloccular approaches), have been described. In this report, we introduce our technique for the retrosigmoid approach and review several extensions as illustrated by schwannoma, meningioma, and epidermoid cyst surgeries.

[Bleeding Control and Dissection in Skull Base Surgery].

Adequate control of bleeding and precise dissection techniques are required at every step of skull base surgery. Prompt identification of bleeding points, appropriate selection of hemostasis technique, and accuracy of the procedure are mandatory. Semi-sharp dissection is a multipurpose technique, while the use of sharp and blunt dissection techniques is based on each situation. In this report, we introduce our hemostasis and dissection techniques, including fibrin glue-soaked hemostatic fabric, Gore-Tex patching, and SS forceps dissection.

Pediatric vestibular schwannoma without evidence of neurofibromatosis: consecutive 18 microsurgical experiences.

PURPOSE: Sporadic vestibular schwannoma (VS) is rare in children in contrast to adults, and detailed investigations of case series of these patients using a single fixed protocol are scarce. This study presents our surgical experience of pediatric VSs without clinical evidence of neurofibromatosis type 2 (NF2) at the initial diagnosis. METHODS: Among 1385 consecutive sporadic VS surgeries, 18 pediatric patients (1.3%; 11-18 years old) were retrospectively investigated. RESULTS: The most common initial symptom was hearing disturbance (72.2%), and 6 patients (33.3%) experienced a delayed diagnosis (over 2 years after initial symptom onset). Preoperative image characteristics of these tumors included a solid tumor, hypervascularity, and significant extension into the internal acoustic meatus, when compared with adults. Preoperative embolization was successfully accomplished for 2 recent hypervascular tumors. The tumor resection rate was 95-100% under sufficient intraoperative neuromonitoring, and no additional surgery was required during the follow-up period (average: 57.9 months). No patients experienced permanent facial nerve palsy, and serviceable hearing function was preserved in 6 of 11 patients. Signs of NF2, such as bilateral VSs, were not identified in any patients during the follow-up. CONCLUSION: Safe and sufficient tumor resection was achieved under detailed neuromonitoring in pediatric patients with sporadic VS, although this tends to be difficult owing to hypervascularity, a small cranium, and significant meatal extension. Preoperative embolization may help safe resection of hypervascular tumors. Subsequent development of NF2 has not been observed up to the most recent follow-up, but careful observation is essential for these younger patients.

Radio-pathological characteristics of malignant transformation of an epidermoid cyst in the cerebellopontine angle: A case report.

Background: Intracranial epidermoid cysts are rare congenital neoplasms that are clinically indolent and histologically benign. They rarely show malignant transformation, and several such cases have been reported. Some radiological features that suggest malignant transformation have been reported. However, histopathological features that indicate a high risk of malignant transformation have not been reported to date. Case Description: We report a 59-year-old woman with a benign epidermoid cyst in the cerebellopontine angle that showed malignant transformation after 6 years. Magnetic resonance imaging (MRI) at the time of initial onset displayed a high-intensity signal on diffusion-weighted imaging (DWI), no peritumoral edema, and no enhancement on contrast-enhanced T1-weighted imaging. On the other hand, MRI at the time of malignant transformation showed a low-intensity signal on DWI, peritumoral edema, and enhancement of the tumor capsule on contrast-enhanced T1-weighted imaging. Pathological findings at the time of the first surgery differed from normal benign epidermoid cysts, in that stratified squamous epithelial metaplasia was observed, and immunohistochemical (IHC) analysis showed positive p53 staining. In addition, IHC analysis at the time of malignant transformation demonstrated positive p16 staining. Conclusion: In benign epidermoid cysts, it is considered to cause malignant transformation when squamous metaplasia or p53 mutation is observed. Therefore, strict follow-up is required while paying attention to the characteristic changes in MRI for early detection and timely treatment of malignant transformation.

Embolization of Skull Base Meningiomas with Embosphere Microspheres: Factors Predicting Treatment Response and Evaluation of Complications.

OBJECTIVE: Preoperative embolization for intracranial meningiomas can cause tumor necrosis, reduce intraoperative blood loss, and facilitate surgery. This study aimed to evaluate the efficacy of tumor embolization using Embosphere microspheres for skull base meningiomas and analyze postembolization plain computed tomography (CT) and magnetic resonance imaging (MRI) scans to identify findings that could potentially predict treatment response. METHODS: Between April 2014 and April 2020, 80 patients with skull base meningiomas presenting at our medical center underwent embolization with Embosphere microspheres. The effects of tumor embolization were evaluated through a comparison of postembolization plain CT and contrast-enhanced MRI. RESULTS: A total of 143 vessels (102 of 108 external carotid artery branches and 41 of 65 internal carotid artery branches) from 80 skull base meningiomas were embolized with Embosphere microspheres. Microspheres 100-300 µm in size were used in 2 cases, microspheres 300-500 µm in size were used in 12 cases, and microspheres 500-700 µm in size were used in 66 cases. Postembolization contrast-enhanced MRI showed reductions in enhancing lesions within the tumor in 55 of 80 cases. Postembolization plain CT scans showed high-density lesions within the tumor in 41 of 55 cases. Thus, reductions in enhancing lesions on postembolization contrast-enhanced MRI were statistically significantly associated with the presence of high-density lesions on postembolization plain CT (P < 0.001). Embolization-related neurological complications occurred in 3 cases. CONCLUSIONS: Embosphere microspheres are user friendly and effective embolic materials for the embolization of skull base meningiomas. Postembolization contrast-enhanced MRI and plain CT findings may be useful for evaluating the effects of tumor embolization.

Preoperative Facial Nerve Palsy in Patients With Vestibular Schwannoma: Clinical Features and Postoperative Functional Prognosis in a Case Series of 34 Among 1228 Consecutive Patients.

BACKGROUND: Facial nerve palsy is a rare presenting symptom of vestibular schwannomas and has not been investigated in detail. OBJECTIVE: To investigate the incidence, clinical features, and postoperative long-term outcomes of facial nerve function in patients with vestibular schwannomas causing preoperative facial nerve palsy. METHODS: After excluding patients with neurofibromatosis type 2 and those with prior treatment, 1228 consecutive patients who underwent vestibular schwannoma surgery were retrospectively investigated. Patients with and without preoperative facial nerve palsy were compared statistically to clarify their clinical features. RESULTS: Preoperative tumoral facial nerve palsy was seen in 34 patients (2.8%). Their clinical features included older age, having large cystic tumors with significant meatal extension, and showing abnormal electrogustometric responses, compared with patients without preoperative facial nerve palsy. Owing to the frequent insufficient intraoperative responses on facial nerve electromyography, the tumor resection rate was lower in the group with preoperative facial nerve palsy (mean: 95.2%). Among the 33 patients with sufficient follow-up data (mean: 63.9 mo), additional treatment was required only in 1 patient and facial nerve function improved in 25 patients (75.8%) within 2 yr postoperatively. CONCLUSION: Facial nerve palsy is a rare preoperative symptom that occurs in less than 3% of patients with vestibular schwannoma. Tumor resection in such patients tends to be challenging owing to their advanced age, having large cystic tumors with significant meatal extension, and difficulties in intraoperative facial nerve monitoring, but surgical decompression of the facial nerve can assist in the improvement of their long-term functions.

Intraoperative Continuous Neuromonitoring for Vestibular Schwannoma Surgery: Real-Time, Quantitative, and Functional Evaluation.

In vestibular schwannoma surgery, neuromonitoring is essential to accomplish sufficient tumor resection while avoiding neurologic damage.1-3 An ideal neuromonitoring method should include a real-time alert system, quantitative evaluation, and functional (not mechanical) assessment.4Video 1 demonstrates facial and hearing preservation surgery for vestibular schwannoma by the retrosigmoid transmeatal approach, under intraoperative continuous facial nerve monitoring and auditory brainstem response. Using a ball-type stimulating electrode placed on the proximal facial nerve, the evoked facial nerve electromyograms were continuously monitored by direct 1-Hz stimulation throughout the near-total tumor resection. The patient had no postoperative facial or hearing deterioration. The patient consented to the procedure before the surgery.

Electronystagmography in 166 patients with acoustic neuroma before and after surgery.

OBJECTIVE: To analyze the preoperative patterns of caloric test, eye tracking test (ETT), and optokinetic pattern (OKP) in patients with acoustic neuroma (AN) and compare them with the postoperative patterns of ETT and OKP results METHODS: A total of 166 patients with AN (102 women; mean age: 41 years, range: 11-79 years) who were being treated at our hospital between 2013 and 2016 were enrolled. Preoperatively, a detailed history was taken regarding the presence of subjective symptoms of equilibrium dysfunction, and the patients underwent caloric test, ETT, and OKP. They were classified into three groups based on the preoperative ETT and OKP results as follows: Group A, normal ETT and OKP; Group B, either ETT or OKP was abnormal; and Group C, both ETT and OKP were abnormal. All patients were evaluated for subjective symptoms of vestibular dysfunction and were also grouped based on the tumor size on imaging. All surgeries were performed by a neurosurgeon using the lateral suboccipital retrosigmoid approach. About one month later after surgery, postoperatively ETT was performed on 150 patients and OKP was performed on 148 patients. The preoperative and postoperative ETT and OKP results were compared. The same two specialists analyzed the postoperative ETT and OKP findings as improved, unchanged, or worse. Student t-test was used for statistical analysis and a P-value of <0.05 was considered to indicate a statistically significant difference. RESULTS: The average canal paresis(CP) % was 65.8%. No correlation was found between tumor size and CP%. The other side, the average tumor size in each group was 26.6 mm, 28.7 mm, and 37.8 mm in the Group A, B, and C, respectively. The average tumor size in Group C was significantly greater than those of Group A and B (P<0.01). The presence of gait disturbance in Group C was significantly higher than the other groups (P<0.01). The other side, abnormal ETT and OKP were seen in 32.5% and 31.9% of all patients, respectively. ETT and OKP results improved postoperatively in 67.4% and 68.9% of these patients. CONCLUSIONS: Abnormal ETT and OKP results showed positive correlations with the tumor size and presence of subjective symptoms. Further, dysfunction of cerebellum and brain stem owing to tumor compression was observed to recover in many cases after surgery.

Preliminary Report: Rapid Intraoperative Detection of Residual Glioma Cell in Resection Cavity Walls Using a Compact Fluorescence Microscope.

OBJECTIVE: The surgical eradication of malignant glioma cells is theoretically impossible. Therefore, reducing the number of remaining tumor cells around the brain-tumor interface (BTI) is crucial for achieving satisfactory clinical results. The usefulness of fluorescence-guided resection for the treatment of malignant glioma was recently reported, but the detection of infiltrating tumor cells in the BTI using a surgical microscope is not realistic. Therefore, we have developed an intraoperative rapid fluorescence cytology system, and exploratorily evaluated its clinical feasibility for the management of malignant glioma. MATERIALS AND METHODS: A total of 25 selected patients with malignant glioma (newly diagnosed: 17; recurrent: 8) underwent surgical resection under photodiagnosis using photosensitizer Talaporfin sodium and a semiconductor laser. Intraoperatively, a crush smear preparation was made from a tiny amount of tumor tissue, and the fluorescence emitted upon 620/660 nm excitation was evaluated rapidly using a compact fluorescence microscope in the operating theater. RESULTS: Fluorescence intensities of tumor tissues measured using a surgical microscope correlated with the tumor cell densities of tissues evaluated by measuring the red fluorescence emitted from the cytoplasm of tumor cells using a fluorescence microscope. A "weak fluorescence" indicated a reduction in the tumor cell density, whereas "no fluorescence" did not indicate the complete eradication of the tumor cells, but indicated that few tumor cells were emitting fluorescence. CONCLUSION: The rapid intraoperative detection of fluorescence from glioma cells using a compact fluorescence microscope was probably useful to evaluate the presence of tumor cells in the resection cavity walls, and could provide surgical implications for the more complete resection of malignant gliomas.