J Neurosurg 115:1147–1157, 2011
Nationwide investigation of the current status of therapeutic neuroendoscopy for ventricular and paraventricular tumors in Japan Clinical article
Nakamasa Hayashi, M.D., Ph.D.,1 Hisayuki Murai, M.D., Ph.D., 2 Shoichiro Ishihara, M.D., Ph.D., 3 Takayuki Kitamura, M.D., Ph.D., 4 Tamotsu Miki, M.D., Ph.D., 5 Tomoru Miwa, M.D., Ph.D., 6 Masakazu Miyajima, M.D., Ph.D.,7 Kenichi Nishiyama, M.D., Ph.D., 8 Takayuki Ohira, M.D., Ph.D.,9 Shigeki Ono, M.D., Ph.D.,10 Tomonari Suzuki, M.D., 3 Shingo Takano, M.D.,11 Ph.D., Isao Date, M.D., Ph.D.,10 Naokatsu Saeki, M.D., Ph.D., 2 and Shunro Endo, M.D., Ph.D.1 1 Department of Neurosurgery, University of Toyama; 2Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba; 3Department of Neurosurgery, Saitama Medical University International Medical Center, Hidaka; 4Department of Neurosurgery, Nippon Medical School, Tokyo; 5 Department of Neurosurgery, Tokyo Medical University, Tokyo; 6Department of Neurosurgery, The Jikei University School of Medicine, Tokyo; 7Department of Neurosurgery, Juntendo University, Tokyo; 8Brain Research Institute, University of Niigata; 9Department of Neurosurgery, Keio University School of Medicine, Tokyo; 10Department of Neurosurgery, Okayama University Graduate School of Medicine, Okayama; and 11 Department of Neurosurgery, University of Tsukuba, Japan
Object. The authors report their investigation on the current status of neuroendoscopic biopsy for ventricular and paraventricular tumors as well as treatment for associated hydrocephalus in Japan. Methods. Patients who had undergone therapeutic neuroendoscopy between 2005 and 2009 were included in this study. The main items examined were age; sex; localization of tumor; pathological diagnosis using biopsy; the presence, treatment, and efficacy of treatment of associated hydrocephalus; perioperative complications; activities of daily living (ADL) before and after therapeutic neuroendoscopy; and the presence of dissemination during the postoperative course. Results. Seven hundred fourteen patients from 123 sites (462 male and 252 female patients, mean age 33.3 years) were enrolled. Localization of the tumor was mainly classified into the lateral ventricle in 91 patients, the third ventricle in 339, the fourth ventricle in 18, the suprasellar region in 75, and other paraventricular areas in 191 patients. The most commonly observed tumors were germ cell tumors in the third ventricle (177 cases [39%]), cystic lesions in the suprasellar region (56 cases [75%]), and astrocytic tumors in the thalamus-basal ganglia (71 cases [38%]). Although 641 (92.8%) of 691 patients could receive neuroendoscopic diagnosis using biopsy, the diagnosis obtained with endoscopic biopsy differed from the final diagnosis based on subsequent craniotomy in 18 patients and clinical course in 3 patients. Of these 21 patients, 7 had astrocytic tumors, 4 had pineal tumors, 6 had germ cell tumors, and 4 had other tumors. The final diagnostic accuracy rate was 89.7%. Associated hydrocephalus was observed in 517 patients (72.4%), of whom 316 and 39 underwent third ventriculostomy and fenestration of the septum, respectively. The response rates were 96.2% and 89.7%, respectively. Third ventriculostomy was required for recurrence of hydrocephalus in 41 patients (13.0%), and the long-term response rate was therefore 83.2% (263 of 316 patients). Perioperative complications other than fever, such as new onset of or progressive hydrocephalus, infection due to CSF leakage, and bleeding in the ventricle or tumor, were found in 81 patients (11.3%). The median Karnofsky Performance Scale score before endoscopic surgery was 80, but it increased to 90 after surgery. The score was thus significantly increased after surgery (p < 0.0001, Mann-Whitney U-test). Activities of daily living after surgery decreased due to perioperative complications in 15 patients (2.1%). The incidence of new dissemination after endoscopic biopsy was 6.8% and not high compared with routine surgical treatment. Conclusions. The authors concluded that neuroendoscopic diagnosis using biopsy for ventricular and paraventricular tumors is adequately accurate and safe. It was demonstrated that endoscopic procedures play important roles not only in the treatment of hydrocephalus associated with intra- and paraventricular tumors but also in significantly improving ADL. Furthermore, the long-term outcome of endoscopic third ventriculostomy was clearly favorable. (DOI: 10.3171/2011.7.JNS101976)
Key Words • brain tumor • endoscopic biopsy • hydrocephalus • septostomy • third ventriculostomy • vascular disorders Abbreviations used in this paper: ADL = activities of daily living; KPS = Karnofsky Performance Scale; VP = ventriculoperitoneal.
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advances in optical technology and surgical instrumentation in neuroendoscopy, the efficacy of neuroendoscopy has come to be widely acknowledged in the field of neurosurgery, particularly for ith
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N. Hayashi et al. intra- and paraventricular lesions.10 Neuroendoscopy is very useful for biopsies, especially of tumors responding to chemotherapy or radiotherapy and in the treatment of associated hydrocephalus, in yielding remarkable efficacy with minimal invasion, and its roles will increase in the future.34,37 While intra- and paraventricular tumors occur infrequently, treatment of them with therapeutic neuroendoscopy is becoming more popular at various institutions in Japan. Especially for cases of noncommunicating hydrocephalus due to tumor, neuroendoscopy has been used for relief of hydrocephalus with tumor biopsy in a single procedure.10,14,26,37 It is sociomedically important to investigate indications and techniques of therapeutic neuroendoscopy as well as treatment-associated complications and clinical results at various institutions, and to demonstrate its contribution to improvement of ADL in patients with intra- and paraventricular tumors. A nationwide investigation by the case registration method has therefore been planned to investigate cases of intra- and paraventricular tumors in which endoscopic biopsy was performed. We attempted to obtain evidence of the diagnostic accuracy and safety of endoscopic tumor biopsy as well as the usefulness of neuroendoscopy for associated hydrocephalus.
Methods
This was an observational study by retrospective investigation of relevant cases, and it was approved by the administrative committee of the Japanese Society of Neuroendoscopy. All patients in the study underwent therapeutic endoscopy between January 2005 and the end of December 2009. Items concerning clinical characteristics and endoscopic procedures were examined in registered patients with ventricular tumors (tumors in the lateral ventricle, third ventricle, or fourth ventricle) and in those with paraventricular tumors that were treatable through the ventricle (Table 1). Histology of brain tumors was classified according to the General Rules for Clinical and Pathological Studies on Brain Tumors established and used in Japan
in accordance with the WHO classification of tumors of the CNS.5 “Accurate diagnosis of biopsy” was assigned when the pathological diagnosis corresponded to the final diagnosis based on the patient’s clinical course and/ or pathological diagnosis on subsequent craniotomy. Presence of hydrocephalus was assessed by clinical symptoms and radiological findings such as ventriculomegaly and obstruction of the CSF pathway by the tumor. “Response to treatment of hydrocephalus” was assessed when the patient’s symptoms and the radiological findings related to hydrocephalus were relieved by treatment. Activities of daily living before and after surgery were assessed using the KPS based on performance status. Accumulation and analysis of cases were performed by the administrative office (Department of Neurosurgery, University of Toyama) after the end of the case registration period. Statistical analysis was performed using the chisquare test and Mann-Whitney U-test.
Results
Seven hundred fourteen patients (462 male and 252 female patients) from 123 institutions were registered in this study. Age ranged from 0 to 85 years (mean 33.3 years). There were 221 children who were younger than 15 years and 84 elderly individuals who were 70 years of age or older. The number of registered patients by institution ranged from 1 to 36, with 20 patients or more registered at 6 institutions, 10–19 patients at 15, and 1–9 patients at 102 institutions. The most common number of registered patients per institution was 1 (33 institutions), and the median of patients per institution was 4. Endoscopy
A flexible scope alone was used in 368 patients (51.5%), a rigid scope alone in 93 (13.0%), and a videoscope (that is, a flexible endoscope with a miniature charge-coupled device at the distal end29) alone in 183 (25.6%). Multiple endoscopes were used in 70 patients.
TABLE 1: Items examined items concerning clinical characteristics of registered patients age, sex, baseline ADL major tumor sites: lat ventricle, 3rd ventricle (including pineal body), 4th ventricle, paraventricular region, & parasellar region pathological diagnosis by endoscopic biopsy presence/absence of hydrocephalic complication & its treatment ADL in period after therapeutic endoscopy & before any additional treatment additional treatment after biopsy: craniotomy, radiotherapy, chemotherapy presence/absence of findings indicative of new dissemination in follow-up & observation periods items concerning endoscopic procedures endoscope used: flexible endoscope, rigid endoscope, or videoscope ventriculoscopic findings: presence/absence of dissemination, findings of tumor hemorrhage intraop issues: hemorrhage control, damage to ventricular structures complications in postbiopsy periop period & patient’s treatment
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Endoscopic tumor biopsy and treatment of associated hydrocephalus Classification by Tumor Location
TABLE 3: Diagnostic success rate by tumor site
Classification by main tumor location was as follows: lateral ventricle (in 91 patients), third ventricle (in 339), fourth ventricle (in 18), suprasellar region (in 75), and other paraventricular areas (in 191 patients) (Table 2). Pineal region tumors are included under the heading of “3rd Ventricle.” The most frequently observed tumors in the lateral ventricle among intraventricular tumors were astrocytic tumors (23.1%) followed by primary malignant lymphomas (18.7%), while germ cell tumors accounted for more than half of the intraventricular tumors (in 177 patients [52.2%]) in the third ventricle. Among tumors in the suprasellar region, there were 56 cystic lesions (74.7%), of which 52 were craniopharyngiomas. Among paraventricular tumors, astrocytic tumors in the basal ganglia were found in 71 cases (37.2%).
No. of Endoscopic Cases Biopsy
Site lat ventricle 3rd ventricle 4th ventricle paraventricular parasellar total
91 339 18 191 75 714
Diagnostic Success & Rate (%)
87 337 10 187 70 691
82 (94.3) 319 (94.7) 9 (90.0) 163 (87.2) 68 (97.1) 641 (92.8)
tricle. The rate of histological diagnosis was high overall: 82 tumors (94.3%) in the lateral ventricle, 319 tumors (94.7%) in the third ventricle, and 9 tumors (90.0%) in the fourth ventricle. It was also high (68 [97.1%] of 70 tumors) in the parasellar region, but lower (163 [87.2%] of 187 tumors) in cases of endoscopic tumor biopsy in the paraventricular region (p < 0.001, chi-square test). Reasons for inability to obtain a diagnosis in 50 patients were as follows: insufficient sampling due to hardness of tumor or bleeding in 22 patients, insufficient sampling of unclear cause in 14 patients, and failure to access the tumor in 14 patients. Endoscopic biopsy was performed in 206 of 221 children younger than 15 years of age; histological diagnosis
Endoscopic Tumor Biopsy
Endoscopic tumor biopsy was performed in 691 patients, while endoscopic observation or treatment for associated hydrocephalus alone was performed in another 23 patients. Histological diagnosis could be performed in 641 (92.8%) of these 691 patients (Table 3). By tumor location, endoscopic biopsy was performed in 87 of 91 tumors in the lateral ventricle, in 337 of 339 tumors in the third ventricle, and in 10 of 18 tumors in the fourth venTABLE 2: Pathological diagnosis and tumor sites
Location Paraventricular
Intraventricular Pathological Diagnosis
Lat 3rd 4th Ventricle Ventricle Ventricle
astrocytic tumor oligodendroglial tumor ependymal tumor choroid plexus tumor glial tumor of uncertain origin neuronal & mixed neuronal-glial tumors pineal tumor embryonal tumor meningeal tumor vascular tumor primary malignant lymphoma & related disorders germ cell tumor cystic lesion pituitary tumor local extension from regional tumor metastatic tumor unclassified tumor vascular malformation & hamartomatous lesion unknown inspection* total
21
29
1 7
11 1 1 2
1 7 2 1 1 39 8 1
17 10 9
16 177 19
3
11 2 2 20 3 339
1 1 1
CerBasal HypoWhite ebel- BrainParaGanglia thalamus Matter lum stem Other sellar Total 71
4
4 1 1 1
1 1 1 2
1
5
10
1
2 1
1
1
1 1 1
17 8 2
5
2
9 1 2
1
4
1 1
2 2 56 2
1
4 4 91
1
2 2
4 1 1
1 8 18
12 2 124
9
1
2
20
3
7 2 31
2 4
1 4 75
146 8 18 3 3 13 40 13 4 3 62 201 95 2 1 21 5 3 50 23 714
* Endoscopic observation or treatment of hydrocephalus alone was performed.
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N. Hayashi et al. had been obtained in 195 (94.7%) of these patients. Commonly observed tumor histologies in children included germ cell tumors in 81 patients (41.5%), astrocytic tumors in 47 patients (24.1%), and cystic lesions in 31 patients (15.9%) (Fig. 1). Histological diagnosis was made with endoscopic biopsy in 74 (88.1%) of 84 elderly patients 70 years of age or older. Commonly observed tumor histologies in the elderly patients included primary malignant lymphomas in 30 patients (40.5%), astrocytic tumors in 14 (18.9%), cystic lesions in 11 (14.9%), and metastatic tumors in 10 patients (13.5%) (Fig. 1). Primary malignant lymphoma, which occurred in 62 cases across all ages, was more common in elderly patients (48.4%); there was only 1 case in a child. The diagnosis obtained with endoscopic biopsy differed from the final diagnosis based on subsequent craniotomy (18 patients) and clinical course (3 patients). The final diagnostic accuracy was 89.7% (Table 4). The time interval between the endoscopic biopsy and craniotomy ranged from 7 days to 39 months. Chemotherapy was administered to 7 patients with (Cases 4 and 5) or without (Cases 1, 3, 6, 8, and 20) radiotherapy prior to the craniotomy. In 1 patient (Case 19), stereotactic radiosurgery was performed. Histologies of tumors with a diagnostic accuracy of 100% were as follows: cystic lesions (95 patients), malignant lymphomas (62 patients), and metastatic tumors (21 patients) among tumors affecting at least 20 patients. In particular, malignant lymphoma and metastatic tumor more commonly occurred in the elderly, suggesting the importance of less-invasive endoscopic biopsy. Outcome of Treatment of Associated Hydrocephalus
Associated hydrocephalus was found in 517 cases (72.4%). By main tumor location, hydrocephalus occurred in 43 (47.3%) of 91 tumors in the lateral ventricle, 284 (83.5%) of 339 tumors in the third ventricle, 18 (100%) of 18 tumors in the fourth ventricle, 48 (64.0%) of 75 suprasellar tumors, and 124 (64.9%) of 191 other paraventricular tumors. The frequency of associated hydrocephalus was higher in the third and fourth ventricles (p < 0.05, chisquare test). Of these 517 patients, third ventriculostomy and fenestration of the septum were performed in 316 and 39 pa-
tients, respectively. Response was obtained in 304 (96.2%) and 35 patients (89.7%), respectively. Other treatment options for associated hydrocephalus included placement of an Ommaya reservoir (35 patients), shunt placement (56 patients), external ventricular drainage (47 patients), and removal of the tumor/cyst (45 patients). The mean follow-up period was 22.7 months in 316 patients who underwent third ventriculostomy. Retreatment of the third ventriculostomy was required for recurrence of hydrocephalus in 41 (13.0%) of 316 patients, and the long-term response rate was therefore 83.2% (263 of 316 patients). The range of time to recurrence was 1 week to 31 months (mean 5.0 months). Treatment for recurrent hydrocephalus involved VP shunt placement (33 patients), ventricular drainage (1 patient), and placement of an Ommaya reservoir (3 patients). Additional fenestration of the floor of the third ventricle was performed in only 4 patients. Complications of Endoscopic Procedures
Complications of endoscopic procedures and the numbers of patients affected are shown in Table 5. Postoperative complications were found in 177 (24.8%) of 714 patients. Patients in whom only fever (defined as body temperature higher than 38°C) occurred as a postoperative complication accounted for 13.6% of cases. Other complications included new onset of or progression of hydrocephalus (2.4%), intraventricular hemorrhage (2.0%), CSF leakage (1.8%), intratumoral hemorrhage (1.4%), seizures (1.0%), eye movement disorder (1.0%), intracerebral hemorrhage along the endoscopic insertion route (0.8%), diabetes insipidus (0.8%), hyponatremia (0.6%), chronic subdural hematoma (0.6%), memory disturbance (0.4%), transient hemiparesis (0.3%), cerebellar hemorrhage (0.1%), prolonged disturbance of consciousness (0.1%), cerebral infarction (0.1%), speech disturbance (0.1%), and confusion (0.1%). Perioperative complications other than fever were found in 81 patients (11.3%). Complications of intratumoral and intraventricular hemorrhage are sometimes clinically silent. The rate of surgical intervention was high for hydrocephalus, at 14 (93.3%) of 15 patients, and for CSF leakage, at 6 (46.2%) of 13 patients. Surgery was performed for intraventricular hemorrhage, intratumoral hemorrhage, and
Fig. 1. Incidence of tumor histologies in 206 children younger than 15 years of age (left), and in 74 elderly patients 70 years of age or older (right) from whom an endoscopic biopsy sample was obtained.
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Endoscopic tumor biopsy and treatment of associated hydrocephalus TABLE 4: Summary of cases with a change in histological diagnosis Case No.
Age (yrs), Sex
Location
Diagnosis by Endoscopic Biopsy
Craniotomy
Interval Btwn Biopsy & Craniotomy
1 2
13, F basal ganglia astrocytoma 35, M 3rd ventricle pineocytoma
yes yes
19 days 12 days
3 4
22, M 3rd ventricle 9, M 3rd ventricle
germinoma germinoma
yes yes
6 mos 3 mos
5 6 7
7, M 3rd ventricle 18, M 3rd ventricle 59, F 3rd ventricle
teratoma germinoma pineocytoma
yes yes yes
3 mos 6 mos 14 mos
8 9 10 11 12 13 14 15 16
23, M 66, F 40, M 19, M 25, M 9, M 66, M 70, F 7, F
3rd ventricle lat ventricle 3rd ventricle 3rd ventricle 3rd ventricle basal ganglia basal ganglia basal ganglia 3rd ventricle
yes yes no yes yes yes no no yes
23 days 19 days 20 days 2 mos 7 days
17 18 19 20 21
63, M 31, F 56, M 5, F 45, M
parasellar 3rd ventricle lat ventricle 3rd ventricle lat ventricle
germinoma anaplastic oligoastrocytoma pilocytic astrocytoma glioblastoma teratoma anaplastic astrocytoma anaplastic astrocytoma anaplastic astrocytoma pineal parenchymal tumor of intermediate differentiation pituitary adenoma pineocytoma astrocytoma choroid plexus papilloma central neurocytoma
yes yes yes yes yes
22 mos 1 mo 39 mos 4 mos 20 days
cerebral hemorrhage in 3 (21.4%) of 14 patients, 2 (20%) of 10 patients, and 1 (16.7%) of 6 patients, respectively. Changes in ADL From Before to After Endoscopic Procedures
Performance status was assessed in 694 patients, excluding those without KPS scores before and after surgery because they were infants or for other reasons. Changes in KPS scores from before to after surgery are shown in Fig. 2. The median KPS score before surgery was 80, which increased to 90 after surgery. The score was thus significantly increased after surgery (p < 0.0001, Mann-Whitney U-test). The KPS score increased after surgery in 348 patients. Associated hydrocephalus occurred in 324 of these patients. It was improved with treatment in 317 patients (Table 6). Endoscopic third ventriculostomy, septostomy, endoscopic partial removal of the tumor, and cystectomy accounted for 83.9% of cases of hydrocephalus treatment. It was thus shown that neuroendoscopy contributes to treatment of hydrocephalus associated with intra- and paraventricular tumors as well as improvement in ADL. Activities of daily living after surgery decreased due to perioperative complications in 15 cases (2.1%; Table 7). Classification by main tumor location was as follows: tumors in the lateral ventricle (6 cases), third ventricle (3 cases), fourth ventricle (1 case), and paraventricular basal
J Neurosurg / Volume 115 / December 2011
9 days
Change in Diagnosis supratentorial primitive neuroectodermal tumors pineal parenchymal tumor of intermediate differentiation mixed germ cell tumor mixed germ cell tumor mixed germ cell tumor teratoma pineal parenchymal tumor of intermediate differentiation embryonal carcinoma anaplastic ependymoma Langerhans cell histiocytosis pilocytic astrocytoma mixed germ cell tumor glioblastoma glioblastoma glioblastoma pineoblastoma pituitary carcinoma pineoblastoma glioblastoma choroid plexus carcinoma ependymoma
ganglia (5 cases). The most frequently observed tumor histology was astrocytic tumor (6 cases), followed by ependymal tumor (3 cases), germinoma (3 cases), craniopharyngioma (1 case), malignant lymphoma (1 case), and unknown (1 case). Complications resulting in decreased ADL were as follows: intratumoral hemorrhage (4 cases), followed by intraparenchymal hemorrhage (2 cases), hydrocephalus (2 cases), memory disturbance (2 cases), intraventricular hemorrhage (1 case), eye movement disorder (1 case), speech disturbance (1 case), diabetes insipidus (1 case), and chronic subdural hematoma (1 case). Dissemination in the CSF Space
Dissemination was found in the CSF space on imaging before surgery in 127 (17.8%) of 714 patients (Table 8). Intraventricular dissemination was observed during endoscopic procedures in 86 (67.7%) of these patients. Endoscopic observation of dissemination was found in 29 (4.9%) of 587 patients with no documented metastasis preoperatively. Dissemination in the CSF space before endoscopic surgeries was found in 156 (21.8%) of 714 cases of intra- and paraventricular tumors. The proportions were higher for embryonal tumors (46.1%) and primary malignant lymphomas (48.3%). In this study, new occurrence of dissemination after endoscopic procedures was reported in 38 patients, cor1151
N. Hayashi et al. TABLE 6: Operative procedures for hydrocephalus in patients whose KPS score was higher after surgery
TABLE 5: Total number of complications Complication
No. of Complications (%)
high fever w/o infection new hydrocephalus intraventricular hemorrhage CSF leakage intratumoral hemorrhage epilepsy eye movement disorder intraparenchymal hemorrhage along the endoscopic approach diabetes insipidus hyponatremia chronic subdural hematoma memory disturbance hemiparesis cerebellar hemorrhage persistent low level of consciousness cerebral infarction speech disturbance confusion
97 (13.6) 17 (2.4) 14 (2) 13 (1.8) 10 (1.4) 7 (1) 7 (1) 6 (0.8) 6 (0.8) 4 (0.6) 4 (0.6) 3 (0.4) 2 (0.3) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1) 1 (0.1)
responding to 6.8% of 558 cases without dissemination before surgery. New occurrence of dissemination after biopsy was most frequently observed with astrocytic tumors (44.7%, 17 cases), followed by malignant lymphomas (5 cases), and germ cell tumors (5 cases). The incidences of this were not high, at 13.9%, 15.6%, and 3.5%, respectively.
Discussion
We investigated the reliability and safety of histological diagnosis with neuroendoscopic biopsy for intra- and paraventricular tumors in Japan by multicenter survey of the current status of therapeutic neuroendoscopy. Registered variables concerning clinical features and endoscopic procedures were retrospectively analyzed for patients with intra- or paraventricular tumors who underwent endoscopic procedures during the preceding 5-year period (2005–2009). In particular, we attempted to show that endoscopic procedures contribute to improvement of
Fig. 2. Graph showing the changes in KPS scores from before to after surgery. 40- indicates a KPS score of 40 or less.
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Procedure
No. of Patients (%)
endoscopic 3rd ventriculostomy 3rd ventriculostomy + septostomy septostomy septostomy + VP shunt resection of tumor/cyst VP shunt Ommaya resovoir external drainage total
266 (83.9) 208 5 15 13 25 20 (6.3) 14 (4.4) 17 (5.4) 317
ADL based on the frequency and treatments of associated hydrocephalus as well as changes in ADL from before to after treatment. Diagnostic Accuracy With Endoscopic Biopsy
Recent studies have reported histological diagnostic accuracies with endoscopic biopsy ranging from 61% to 100% for intra- and paraventricular tumors.2,4,9,10,21,26, 30,31,36,37 These studies included reports on relatively small numbers of patients, from 6 to 47; no reports on large numbers of patients were found. This study used the case registration method and included 123 institutions in Japan. The number of patients per institution was not large, at 1 to 36, over 5 years, although the total number of patients was large (714). The histological diagnostic accuracy in this study was 92.8%, which is comparable to that in previous reports. The histological diagnostic accuracy with endoscopic biopsy was 94.7% in children younger than 15 years of age, which corresponded to 70%–100% in previously reported studies.1,29,34 By location, diagnostic accuracy with endoscopic biopsy was significantly lower for paraventricular tumors. Diagnosis could not be made due to technical problems in endoscopic procedures such as tumor hardness or insufficient sampling due to bleeding in 22 of 50 patients and failure to access the tumor in 14 patients. Fiorindi and Longatti9 reported that endoscopic biopsy yielded a pathological diagnosis in 19 (82.6%) of 23 patients. They noted that insufficient specimens were the main factor in the 4 patients in whom a diagnosis was not obtained. Furthermore, one major problem in endoscopic management of tumors is hemostasis. Small hemorrhages occur during nearly all tumor biopsies, and even a small amount of bleeding can completely obscure the operative view. In many cases, it can be controlled by irrigation, although biopsy is sometimes interrupted due to difficulties with hemostasis when arterial bleeding occurs. The development of a reliable means of hemostasis is required. The diagnosis obtained with endoscopic biopsy differed from the final diagnosis on subsequent craniotomy or based on clinical course in 21 (3.3%) of 641 patients with a diagnostic biopsy. Final diagnostic accuracy was thus decreased to 89.7%. Depreitere et al.6 also indicated J Neurosurg / Volume 115 / December 2011
Endoscopic tumor biopsy and treatment of associated hydrocephalus TABLE 7: Summary of cases with decreased KPS score Case Age (yrs), No. Sex 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
29, F 29, M 51, F 77, F 26, F 29, M 24, M 74, M 51, F 42, M 59, M 45, M 21, M 65, F 11, F
KPS Score Location
Pathological Diagnosis
Preop
Postop*
Complication
lat ventricle basal ganglia 3rd ventricle lat ventricle 3rd ventricle basal ganglia basal ganglia 4th ventricle lat ventricle 3rd ventricle lat ventricle lat ventricle lat ventricle basal ganglia basal ganglia
glioblastoma astrocytoma craniopharyngioma subependymoma astrocytoma germinoma unknown malignant lymphoma anaplastic astrocytoma germinoma subependymoma ependymoma germinoma astrocytoma glioblastoma
50 80 50 70 100 80 90 50 60 90 90 100 90 80 80
40− 40− 40− 60 40− 70 60 40− 40− 80 80 70 80 40− 70
intraparenchymal hemorrhage intratumoral hemorrhage diabetes insipidus chronic subdural hematoma intratumoral hemorrhage memory disturbance memory disturbance intraventricular hemorrhge intratumoral hemorrhage eye movement disorder speech disturbance hydrocephalus intraparenchymal hemorrhage intratumoral hemorrhage hydrocephalus
* A score of 40− indicates a KPS score of 40 or less.
that the histological diagnosis obtained with endoscopic biopsy may differ from that obtained with subsequent craniotomy. They suggested various reasons for this, such as small biopsy size and crushing artifacts in samples. Moreover, they stated that it is desirable to obtain large,
numerous, and intact samples for accurate histological diagnosis, and that it is important to use large biopsy forceps with a rigid endoscope.6 In our study, the time interval between the endoscopic biopsy and the craniotomy ranged from 7 days to 39 months, and chemo- and radio-
TABLE 8: Case numbers and incidence of dissemination Pathological Diagnosis astrocytic tumor oligodendroglial tumor ependymal tumor choroid plexus tumor glial tumor of uncertain origin neuronal & mixed neuronal-glial tumors pineal tumor embryonal tumor meningeal tumor vascular tumor primary malignant lymphoma & related disorders germ cell tumor cystic lesion pituitary tumor local extension from regional tumor metastatic tumor unclassified tumor vascular malformation & hamartomatous lesion unknown inspection total
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No. of Preprocedural Suspected Unsuspected Cases w/o New Dissemination Cases Dissemination (%) Preop Preop Dissemination After Procedure (%) 146 8 18 3 3 13 40 13 4 3 62 201 95 2 1 21 5 3 50 23 714
24 (16.4) 1 (12.5) 6 (33.3)
18 1 5
6 1
1 (7.7) 8 (20.0) 6 (46.1)
1 7 6
1
30 (48.3) 57 (28.4) 3 (3.2)
25 46 2
5 11 1
1 (100) 7 (33.3)
1 4
8 (16.0) 4 (17.4) 156 (21.8)
7 4 127
3
1 29
122 7 12 3 3 12 32 7 4 3 32 144 92 2
17 (13.9)
14 5 3 42 19 558
1 (7.1)
1 (33.3) 1 (8.3) 2 (6.3) 2 (28.6)
5 (15.6) 5 (3.5) 1 (50)
3 (7.1) 38 (6.8)
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N. Hayashi et al. therapy were performed in 8 of 18 patients following the endoscopic biopsy and prior to craniotomy. The second specimen obtained by craniotomy might have been affected by chemo- and radiotherapy and therefore may not truly be representative of tumor histology. There were 21 patients whose initial endoscopic biopsy diagnosis differed from the final diagnosis (which was based on subsequent craniotomy or clinical course); the final diagnosis in 7 of these patients was astrocytic tumor, which accounts for 4.8% of the 146 astrocytic tumors. The cause was variation in grade in 5 of 7 cases. The rate of change in final diagnosis was high even for pineal region tumors. The final diagnosis with endoscopic biopsy differed from endoscopic results in 6 (3.0%) of 201 patients with germ cell tumor and in 4 (10%) of 40 patients with pineal tumor. O’Brien et al.26 reported that of 33 patients in whom an endoscopic tumor biopsy was performed, histological findings for the specimens were nondiagnostic in 8 (24%), and of these, 7 involved pineal region tumors. They noted that endoscopic tumor biopsy is probably less accurate than frame-based stereotactic biopsy in establishing a histological diagnosis for tumors in the pineal region, since the diagnostic accuracy obtained with stereotactic frame-based biopsy is reported to be 97%.17 Yamini et al.36 also reviewed the literature on endoscopic biopsy for pineal region tumors and reported that a positive tissue diagnosis was established in 89% of 54 cases. Treatment for a pineal region tumor may involve aggressive resection, radiotherapy, chemotherapy, or a combination of these based on tumor histology.7,16,23,24,27 Obtaining an adequate tissue sample for histological diagnosis is an important part of treatment planning. Some types of tumors may not require microsurgical resection. In the treatment of pineal parenchymal tumors, stereotactic radiosurgery yields a high tumor control rate and is a valuable primary management modality.13 Germinoma is one of the most radiosensitive tumors of the CNS, and obtaining tumor specimens with minimal invasion and pathological diagnosis are thus of great importance before radiotherapy.26–28,37 Initial endoscopic management of pineal region tumors and associated hydrocephalus is becoming more standard.8,12,28,31,32,36 Neuroendoscopy is a minimally invasive way of meeting the following objectives with onestep surgery in the management of pineal region tumors: 1) CSF sampling for analysis of tumor markers, 2) treatment of hydrocephalus by third ventriculostomy, and 3) tumor biopsy for histological diagnosis. Biopsy specimens can be obtained to identify tumors that will require further open surgery or adjuvant radiation and/or chemotherapy, since pineal region tumors are very likely to be chemo- or radiosensitive.8,12,28 In the present study, histological diagnosis was not obtained by endoscopic biopsy in 2 of 177 germ cell tumors in the pineal region, and the final diagnosis differed from endoscopic results in 6 of 175 cases whose histological diagnosis was obtained by endoscopic biopsy. Although the diagnostic accuracy for germ cell tumors was 96.6% (169 of 175 tumors), comparable to that of stereotactic frame-based biopsy, the final diagnosis differed from endoscopic results in 3.4% (6 of 175 tumors) of cases of germ cell tumor in the pineal region. Effort to obtain 1154
higher diagnostic accuracy by endoscopic biopsy is thus required. In contrast, the types of tumor histology with high diagnostic accuracies were cystic lesions, malignant lymphomas, and metastatic tumors. These tumors more frequently occurred in elderly patients in this study, with incidences of primary malignant lymphoma, cystic lesions, and metastatic tumor in 40.5%, 14.9%, and 13.5%, respectively. Malignant lymphomas occurred more commonly in the paraventricular region, although in all such cases the histology could be determined with endoscopic biopsy. Moreover, no tumors were found in which the diagnosis differed from that on endoscopic diagnosis, suggesting that reliable histological diagnosis is possible. The diagnostic accuracy was also 100% with endoscopic biopsy of metastatic tumors. Many of these tumors were radio- and chemosensitive, indicating the importance of less-invasive endoscopic biopsy. Treatment for Associated Hydrocephalus and its Outcome
For cases of noncommunicating hydrocephalus in particular, neuroendoscopy enables combining relief of hydrocephalus with tumor biopsy and CSF sampling in a single procedure.10,14,26,32,37 It has been reported that the incidence of associated hydrocephalus is high, particularly with pineal tumors.8,12,28 In this study, associated hydrocephalus was found in 517 (72.4%) of 714 patients with intra- and paraventricular tumors. Its frequency was significantly higher in tumors in the third or fourth ventricle. Certain endoscopic procedures including fenestration of the floor of the third ventricle or septum pellucidum may be selected on the basis of the reason for impairment of CSF circulation. It has been reported that one-trajectory procedures performed using a flexible scope are useful in treating tumors.9,26 In the present study, more than half of the patients underwent treatment using a flexible scope alone. In Japan, a Japanese-made videoscope (VEF-V, Olympus Medical Systems) has been used in many institutions. This videoscope is steerable and has good operational characteristics as a flexible scope, and onetrajectory procedures are possible with it. Furthermore, the quality of the images obtained with the videoscope are quite excellent.29 The response rate has been reported to be 85%–96% with third ventriculostomy for associated hydrocephalus.12,18,21 On long-term follow-up, the response rate was somewhat lower, at 68%–83%, although adequate, suggesting a satisfactory long-term outcome.18,21,26 The response rate was also satisfactory in the short term, at 96.2%, and long term (mean follow-up period 22.7 months), at 83.2%, in the present study. This outcome is comparable to previously reported long-term outcomes (74%–86.4%) of third ventriculostomy for noncommunicating hydrocephalus,11,15,33,35 demonstrating the long-term usefulness of endoscopic fenestration of the third ventricle for neoplastic lesions. However, some occurrences of late-onset obstruction of the region of fenestration due to extension of tumor have recently been reported in patients with tumors in the third ventricle, indicating that careful follow-up is needed.22,25 In the present study, retreatment for recurrence J Neurosurg / Volume 115 / December 2011
Endoscopic tumor biopsy and treatment of associated hydrocephalus of hydrocephalus after third ventriculostomy was required in 13% of cases. These cases were usually treated by shunt placement and endoscopic observation of the previously treated floor of the third ventricle in 4 cases. In all cases, membranous occlusion of the stoma was found and additional fenestration of the floor of the third ventricle was performed. Complications of Endoscopic Procedures
There have been some reports on types of complications and their incidence with endoscopic biopsy for intra- and paraventricular tumors in addition to endoscopic procedures for associated hydrocephalus. Gaab and Schroeder10 reported that among 30 such patients, there was 1 case of meningitis, 1 of mutism, 2 of memory loss attributed to injury of the fornix, 1 of transient trochlear palsy after a biopsy specimen of an aqueductal tumor was obtained, and 1 of transient confusion after a biopsy specimen of a germinoma was obtained. They also reported that there were no endoscopy-related deaths.10 Beems and Grotenhuis3 reported that they observed complications related to endoscopic procedures in 8 of 41 patients with noncommunicating hydrocephalus caused by intra- or paraventricular tumor, including 1 case of ventriculitis, 1 of late arousal, 1 of hemiparesis, 2 of Parinaud syndrome, 2 of intraventricular hematoma, and 1 of intratumoral hematoma. Yamini et al.36 reported a rate of transient complications of 15%, with no deaths. It has also been reported that the incidence of complications including cardiovascular complications (for example, interruption of surgical procedures due to bleeding during endoscopic biopsy of tumors or bradycardia during surgery) and various adverse events (for example, endocrine function disorders) was 31%. The incidence of complications was high, at 24.8%, including intraventricular hemorrhage and intratumoral hemorrhage not requiring operative treatment, intracerebral hemorrhage along the insertion route, eye movement disorder, electrolyte abnormality, and fever without sign of infection in the present study. Many of the complications associated with endoscopic procedures were transient and often improved spontaneously or with appropriate treatment.3 It has been reported that the incidence of clinically apparent complications with such procedures was 7%.1 Recently, a low rate of hemorrhagic complications (3.5%) after endoscopic biopsy of the intraventricular tumor has been reported.19 Complications resulting in a decrease in ADL after surgery were clinically observed in 15 patients (2.1%), suggesting that endoscopic procedures could have been safely performed in this study. Decreases in ADL were more common in the case of lateral ventricular or paraventricular basal ganglia tumors as well as astrocytic tumors and were often caused by hemorrhagic complications associated with endoscopic tumor biopsy. Intratumoral hemorrhage in addition to intraventricular hemorrhage was found in 5 of 15 patients. Moreover, memory disturbance due to injury of the fornix, an important intraventricular structure, was found in 2 patients. Attention should be focused most on one of the complications, namely bleeding associated with tumor biopsy J Neurosurg / Volume 115 / December 2011
during surgery.8,10 The intraventricular CSF becomes opacified after bleeding and obscures the operative view even with repeated rinsing. This may result in injury of intraventricular structures. The best control of hemorrhage is prevention.4 Detailed preoperative evaluation of the tumor vasculature, based on the type of contrast enhancement on CT scans and MR images, and/or digital subtraction angiograms, should be considered. Change in Performance Status From Before to After Endoscopic Procedures
In this study, we investigated the change in performance status before endoscopic procedures, as well as before additional treatment after endoscopic tumor biopsy and treatment of associated hydrocephalus. Statistically significant improvement in performance status after endoscopic procedures was observed compared with that before them. The main reason for this was improvement of associated hydrocephalus, and the proportion of endoscopic procedures was therefore 83.9%. It was shown that neuroendoscopy contributes to the treatment of hydrocephalus associated with intra- and paraventricular tumors as well as improvement in ADL.
Dissemination
Neuroendoscopic surgery allows direct visualization of the ependymal surface for diagnosis of unsuspected metastases.34 Unsuspected metastases were found in 4.9% of patients even in our research study. Imaging and endoscopic findings revealed that dissemination prior to biopsy was more common in the case of embryonal tumors and primary malignant lymphomas. It has been pointed out that endoscopic biopsy may cause dissemination in the CSF space.4,20 Literature reviews have shown that the incidence of dissemination in the CSF space after surgery is 5%–10% in the case of pilocytic astrocytoma, 15%–20% in that of high-grade glioma, and 10%–15% in the case of pineal parenchymal tumors.20 In this study, the incidence of new dissemination after endoscopic biopsy was 6.8%. Newly occurring dissemination was more common in the case of astrocytic tumors, followed by malignant lymphomas and germ cell tumors, although the incidences of this were only 13.9%, 15.6%, and 3.5%, respectively, and not high compared with routine surgical treatment. However, the determination of whether dissemination existed before and after surgery depended on imaging findings alone, and the incidence observed may not accurately reflect that of new dissemination after surgery. Since radiological examination of the spinal axis was not required in this study, dissemination along the spinal axis after endoscopic biopsy might have been overlooked. A prospective study of the involvement of endoscopic biopsy in dissemination is required, with use of a detailed protocol. Limitations of the present study include its vague definition of hydrocephalus and of success of treatment of hydrocephalus without objective assessment, a limited follow-up period after endoscopic treatment, and the small number of patients enrolled at most institutions. 1155
N. Hayashi et al. Conclusions
In this study, we investigated the accuracy and safety of histological diagnosis with neuroendoscopic biopsy for intra- and paraventricular tumors in Japan as well as the usefulness of treatments for associated noncommunicating hydrocephalus. Endoscopic biopsy may permit differentiation of cases requiring a microsurgical approach from those to be treated with irradiation and/or chemotherapy alone. Endoscopic tumor biopsy is most strongly indicated for tumors for which postsurgical treatments such as chemotherapy or radiotherapy are effective. Among such tumors, the final diagnosis differed from endoscopic results in about 3% of germ cell tumors in the pineal region, and effort to obtain higher diagnostic accuracy by endoscopic biopsy is required. Chemotherapy or radiotherapy is also effective for metastatic brain tumors and malignant lymphomas. These tumors are more frequent and less invasive, with a low incidence of complications, allowing safe performance of biopsy in elderly patients. The diagnostic accuracy of endoscopic biopsy was high for these tumors. It was demonstrated that endoscopic procedures play important roles not only in the treatment of hydrocephalus associated with intra- and paraventricular tumors but also in significantly improving ADL. Furthermore, the long-term outcome of endoscopic third ventriculostomy was clearly favorable. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Hayashi, Ohira, Endo. Acquisition of data: Hayashi, Murai, Ishihara, Kitamura, Miki, Miwa, Miyajima, Nishiyama, Ohira, Ono, Suzuki, Takano. Analysis and interpretation of data: Hayashi. Drafting the article: Hayashi. Study supervision: Date, Saeki, Endo. References 1. Ahn ES, Goumnerova L: Endoscopic biopsy of brain tumors in children: diagnostic success and utility in guiding treatment strategies. Clinical article. J Neurosurg Pediatr 5:255–262, 2010 2. Badie B, Brooks N, Souweidane MM: Endoscopic and minimally invasive microsurgical approaches for treating brain tumor patients. J Neurooncol 69:209–219, 2004 3. Beems T, Grotenhuis JA: Long-term complications and definition of failure of neuroendoscopic procedures. Childs Nerv Syst 20:868–877, 2004 4. Chernov MF, Kamikawa S, Yamane F, Ishihara S, Kubo O, Hori T: Neurofiberscopic biopsy of tumors of the pineal region and posterior third ventricle: indications, technique, complications, and results. Neurosurgery 59:267–277, 2006 5. Committee of Brain Tumor Registry of Japan, Japanese Pathological Society (eds): General Rules for Clinical and Pathological Studies on Brain Tumors. Tokyo: Kanehara, 1995 6. Depreitere B, Dasi N, Rutka J, Dirks P, Drake J: Endoscopic biopsy for intraventricular tumors in children. J Neurosurg (5 Suppl) 106:340–346, 2007 7. Edwards MS, Hudgins RJ, Wilson CB, Levin VA, Wara WM: Pineal region tumors in children. J Neurosurg 68:689–697, 1988
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8. Ferrer E, Santamarta D, Garcia-Fructuoso G, Caral L, Rumià J: Neuroendoscopic management of pineal region tumours. Acta Neurochir (Wien) 139:12–21, 1997 9. Fiorindi A, Longatti P: A restricted neuroendoscopic approach for pathological diagnosis of intraventricular and paraventricular tumours. Acta Neurochir (Wien) 150:1235–1239, 2008 10. Gaab MR, Schroeder HW: Neuroendoscopic approach to intraventricular lesions. J Neurosurg 88:496–505, 1998 11. Gangemi M, Donati P, Maiuri F, Longatti P, Godano U, Mascari C: Endoscopic third ventriculostomy for hydrocephalus. Minim Invasive Neurosurg 42:128–132, 1999 12. Gangemi M, Maiuri F, Colella G, Buonamassa S: Endoscopic surgery for pineal region tumors. Minim Invasive Neurosurg 44:70–73, 2001 13. Hasegawa T, Kondziolka D, Hadjipanayis CG, Flickinger JC, Lunsford LD: The role of radiosurgery for the treatment of pineal parenchymal tumors. Neurosurgery 51:880–889, 2002 14. Hellwig D, Grotenhuis JA, Tirakotai W, Riegel T, Schulte DM, Bauer BL, et al: Endoscopic third ventriculostomy for obstructive hydrocephalus. Neurosurg Rev 28:1–38, 2005 15. Hopf NJ, Grunert P, Fries G, Resch KD, Perneczky A: Endoscopic third ventriculostomy: outcome analysis of 100 consecutive procedures. Neurosurgery 44:795–806, 1999 16. Jooma R, Kendall BE: Diagnosis and management of pineal tumors. J Neurosurg 58:654–665, 1983 17. Kreth FW, Schätz CR, Pagenstecher A, Faist M, Volk B, Ostertag CB: Stereotactic management of lesions of the pineal region. Neurosurgery 39:280–291, 1996 18. Kwiek SJ, Mandera M, Baowski P, Luszawski J, Duda I, Wolwender A, et al: Endoscopic third ventriculostomy for hydrocephalus: early and late efficacy in relation to aetiology. Acta Neurochir (Wien) 145:181–184, 2003 19. Luther N, Cohen A, Souweidane MM: Hemorrhagic sequelae from intracranial neuroendoscopic procedures for intraventricular tumors. Neurosurg Focus 19(1):E9, 2005 20. Luther N, Stetler WR Jr, Dunkel IJ, Christos PJ, Wellons JC III, Souweidane MM: Subarachnoid dissemination of intraventricular tumors following simultaneous endoscopic biopsy and third ventriculostomy. Clinical article. J Neurosurg Pediatr 5:61–67, 2010 21. Macarthur DC, Buxton N, Punt J, Vloeberghs M, Robertson IJ: The role of neuroendoscopy in the management of brain tumours. Br J Neurosurg 16:465–470, 2002 22. Massimi L, Tamburrini G, Caldarelli M, Di Rocco F, Federica N, Di Rocco C: Late closure of the stoma by spreading of a periaqueductal glioma: an unusual failure of endoscopic third ventriculostomy. Case report. J Neurosurg 104 (3 Suppl): 197–201, 2006 23. Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, et al: Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86:446–455, 1997 24. Nicholson JC, Punt J, Hale J, Saran F, Calaminus G: Neurosurgical management of paediatric germ cell tumours of the central nervous system—a multi-disciplinary team approach for the new millennium. Br J Neurosurg 16:93–95, 2002 25. Nigri F, Telles C, Acioly MA: Late obstruction of an endoscopic third ventriculostomy stoma by metastatic seeding of a recurrent medulloblastoma. Case report. J Neurosurg Pediatr 5:641–644, 2010 26. O’Brien DF, Hayhurst C, Pizer B, Mallucci CL: Outcome in patients undergoing single-trajectory endoscopic third ventriculostomy and endoscopic biopsy for midline tumors presenting with obstructive hydrocephalus. J Neurosurg 105 (3 Suppl):219–226, 2006 27. Oi S, Matsumoto S: Controversy pertaining to therapeutic modalities for tumors of the pineal region: a worldwide survey of different patient populations. Childs Nerv Syst 8:332–336, 1992
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Endoscopic tumor biopsy and treatment of associated hydrocephalus 28. Oi S, Shibata M, Tominaga J, Honda Y, Shinoda M, Takei F, et al: Efficacy of neuroendoscopic procedures in minimally invasive preferential management of pineal region tumors: a prospective study. J Neurosurg 93:245–253, 2000 29. Oka K: Introduction of the videoscope in neurosurgery. Neurosurgery 62 (5 Suppl 2):ONS337–ONS341, 2008 30. Oka K, Kin Y, Go Y, Ueno Y, Hirakawa K, Tomonaga M, et al: Neuroendoscopic approach to tectal tumors: a consecutive series. J Neurosurg 91:964–970, 1999 31. Pople IK, Athanasiou TC, Sandeman DR, Coakham HB: The role of endoscopic biopsy and third ventriculostomy in the management of pineal region tumours. Br J Neurosurg 15:305–311, 2001 32. Robinson S, Cohen AR: The role of neuroendoscopy in the treatment of pineal region tumors. Surg Neurol 48:360–367, 1997 33. Scarrow AM, Levy EI, Pascucci L, Albright AL: Outcome analysis of endoscopic III ventriculostomy. Childs Nerv Syst 16:442–445, 2000 34. Song JH, Kong DS, Shin HJ: Feasibility of neuroendoscopic biopsy of pediatric brain tumor. Childs Nerv Syst 26:1593–1598, 2010
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35. Teo C, Rahman S, Boop FA, Cherny B: Complications of endoscopic neurosurgery. Childs Nerv Syst 12:248–253, 1996 36. Yamini B, Refai D, Rubin CM, Frim DM: Initial endoscopic management of pineal region tumors and associated hydrocephalus: clinical series and literature review. J Neurosurg 100 (5 Suppl Pediatrics):437–441, 2004 37. Yurtseven T, Erşahin Y, Demirtaş E, Mutluer S: Neuroendoscopic biopsy for intraventricular tumors. Minim Invasive Neurosurg 46:293–299, 2003
Manuscript submitted November 23, 2010. Accepted July 18, 2011. Please include this information when citing this paper: published online August 12, 2011; DOI: 10.3171/2011.7.JNS101976. Address correspondence to: Nakamasa Hayashi, M.D., Ph.D., Department of Neurosurgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. email: nakamasa @med.u-toyama.ac.jp.
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