Yukihiko Sonoda

Impact of gross total resection in patients with WHO grade III glioma harboring the IDH 1/2 mutation without the 1p/19q co-deletion.

The prognosis of patients with WHO grade III gliomas is highly dependent on their genomic status such as the isocitrate dehydrogenase (IDH) 1/2 mutation and1p/19q co-deletion. However, difficulties have been associated with determining which tumors have certain genomic profiles by preoperative radiographical modalities, and the role of surgical resection in achieving better outcomes remains unclear. This retrospective study included 124 consecutive patients with newly diagnosed grade III gliomas. The genomic status of IDH1/2 and 1p/19q was analyzed in these patients. Tumors were then divided into 3 subgroups based on their genomic status; the IDH 1/2 mutation with the 1p/19q co-deletion (1p/19q co-del), the IDH 1/2 mutation without the 1p/19q co-deletion (non-1p/19q co-del), and the IDH 1/2 wild type (IDH wt). Survival times were compared between patients who underwent gross total resection and those who did not (GTR versus non-GTR). The relationships between genomic statuses and MR imaging characteristics such as ring-like or nodular enhancements by gadolinium, and very low intensity on T1-weighted images with blurry enhancements (T1VL) were also examined. Among all patients with grade III gliomas, GTR patients had longer median survival and progression-free times than those of non-GTR patients (undefined versus 87xa0months, pu2009=u20090.097, and 124 versus 34xa0months, pu2009=u20090.059, respectively). No significant differences were observed in survival between GTR and non-GTR patients in the 1p/19q co-del group (pu2009=u20090.14), or between GTR and non-GTR patients in the IDH wt group (26 and 27xa0months, pu2009=u20090.29). On the other hand, in non-1p/19q co-del group, survival was significantly longer in GTR patients than in non-GTR patients (undefined versus 77xa0months, pu2009=u20090.005). Radiographically, T1VL was detected in most tumors in the non-1p/19q co-del group (78.2u2009%), but only 6 (21.4u2009%) and 17 (41.5u2009%) tumors in the 1p/19q co-del and IDH wt groups, respectively. A correlation was not found between other genomic subgroups and MR imaging findings. Strict surgical removal is important to improve the prognosis of patients with grade III gliomas, especially for tumors with the IDH 1/2 mutation without the 1p/19q co-deletion. The MR finding of T1VL can be used to select candidates for more radical resection.

Surgical resection of tumors located in subcortex of language area.

SummaryObject. Although functional mapping facilitates the planning of surgery in and around eloquent areas, the resection of tumors adjacent to language areas remains challenging. In this report, we took notice that the language areas (Broca’s and Wernicke’s) present at the perisylvian fissure. We posit that if there is non-essential language area on the inner surface of the Sylvian fissure, safe tumor resection may be possible even if the tumor is located under the language cortex.n Methods. The study population consisted of 5 patients with intrinsic brain tumors (frontal glioma, n = 3; temporal cavernous angioma, n = 1; primary malignant central nervous system lymphoma, n = 1) located in the perisylvian subcortex, in the language-dominant hemisphere. All patients underwent awake surgery and we performed intra-operative bipolar cortical functional language mapping. When the tumor was located under the language area, the Sylvian fissure was opened and the inner surface of the opercular cortex was exposed with the patient asleep, and additional functional mapping of that cortex was performed. This enabled us to remove the tumor from the non-functioning cortex.In our series, 4 of 5 patients had not language function on the inner surface of the operculum. Only one patient, a 52-year-old man with frontal glioblastoma (Case 3) had language function on the inner surface of the frontal operculum.n Conclusion. We suggest that even perisylvian tumors located in the subcortex of the language area may be resectable via the nonfunctioning intrasylvian cortex by a transopercular approach without resultant language dysfunction.

Multimodal strategy for managing meningiomas in the elderly

SummaryBackground. The incidence of brain tumors in elderly patients is increasing. It has become possible to treat meningiomas in the elderly by several modalities. We developed a successful multimodal strategy to treat these patients.Methods. We registered 35 patients with meningiomas. Symptomatic meningiomas were treated surgically at the time of diagnosis (n=19). Of the 16 asymptomatic meningiomas, 5 were removed at the time of diagnosis. The other asymptomatic meningiomas (n=11) were treated conservatively and when the tumors increased in size, surgical treatment was considered. “Operated” patients with residual or recurrent tumors underwent radiosurgery with a gamma knife.Findings. Surgical mortality and morbidity were 4% and 16%, respectively. Of the 25 “operated” patients, 21 (84.0%) had a good Karnofsky scale (≥80%) at discharge. In all but two of the 11 patients with asymptomatic, conservatively treated meningiomas, the tumors did not increase during the follow-up period. Gamma knife radiosurgery, performed to treat 3 residual and 1 recurrent tumor, resulted in very good tumor control and none of the tumors increased after gamma knife surgery.Conclusions. Meningiomas in elderly patients require a multimodal approach. Our strategy, which includes surgery, radiosurgery, and conservative treatment, resulted in good tumor control and made it possible for patients to pursue their activities of daily life.

Analysis of the extent of astrocytic tumour resection evaluated by magnetic resonance images

One of the most important prognostic factors in brain tumours is the extent of tumour resection. Its evaluation has been difficult on computed tomography (CT); however, magnetic resonance imaging (MRI) can clearly determine the extent of tumour resection. Using MRI, we analyzed 77 patients with astrocytic tumours that were surgically treated at our department from 1994 to 2001. The tumours were classified into the following types: (a) well-circumscribed: single lesions that can be distinguished from normal brain; (b) localised: single lesions that are localised in one gyrus; and (c) diffuse: other tumours. Our treatment of glioma resection is to use sulcus opening and gyrectomy, a technique based on identification and dissection of the sulcus adjacent to the tumour followed by en bloc tumour resection. Almost total tumour resection (≥95% resection) was achieved in 76.8% in the well-circumscribed type, 100% in the localised type, and only 10.5% in the diffuse type. Nearly total resection was achieved in 61%, which is considerably more than in the literature of the CT era (10.4–23.5%). The sulcus opening and gyrectomy technique based on MRI achieved radical glioma removal in cases which could be identified by MRI, resulting in a better tumour removal rate than that based on CT.

Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; pu2009=u20090.0039 and 26.9 vs. 18.6 months; pu2009=u20090.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

A segmental copy number loss of the sfmbt1 gene is a genetic risk for shunt-responsive, idiopathic normal pressure hydrocephalus (inph): A case-control study

Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82–23.79, p = 1.8 x 10−5) and 6.3% of patients with Parkinson’s disease (n = 32) (OR = 5.18, 95%CI: 1.1–50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.

Correlation between hypoxic area in primary brain tumors and WHO grade: differentiation from malignancy using 18F-fluoromisonidazole positron emission tomography

Background 18F-fluoromisonidazole positron emission tomography (FMISO-PET) has been used for identification of hypoxic areas in tumors, and since hypoxia causes hypoxia-inducible factor-1 and enhancement of tumor growth, identifying the hypoxic area in the tumor tissue is important. Purpose To evaluate the usefulness of FMISO-PET in the grading of primary brain tumors. Material and Methods FMISO-PET was performed preoperatively on 41 consecutive patients with pathologically confirmed brain tumor. A neuroradiologist retrospectively measured both maximum standardized uptake value (SUVmax) and mean SUV (SUVmean) in the tumor and normal cerebellar parenchyma. Maximum tumor/normal control ratio (T/Nmax) and mean tumor/normal control ratio (T/Nmean) were calculated and analyzed. Results There was a positive correlation between World Health Organization (WHO) grade and both T/Nmax and T/Nmean (ru2009=u20090.731 and 0.713, respectively). When all cases were divided into benign (WHO grade II) and malignant groups (III and IV), there were significant differences between the two groups in both T/Nmax and T/Nmean (Pu2009<u20090.001). If the cutoff value was defined as T/Nmaxu2009=u20091.25 and T/Nmeanu2009=u20091.23, T/Nmax had a sensitivity of 90.0% and a specificity of 90.9% while T/Nmean had a sensitivity of 93.3% and a specificity of 90.9% in differentiating the benign group from the malignant group. Conclusion Both T/Nmax and T/Nmean in FMISO-PET have a positive correlation with primary brain tumor grading, making FMISO-PET useful in diagnosing the malignancy of primary brain tumors.

Clinical Features of Precocious, Synchronous, and Metachronous Brain Metastases and the Role of Tumor Resection

OBJECTIVEnThe purpose of this study was to clarify clinical features, outcomes, and the role of tumor resection in precocious, synchronous, and metachronous brain metastases.nnnMETHODSnBrain metastases were found before primary cancer detection in the precocious group, within 2 months after primary cancer detection in the synchronous group, and 2 months or later after primary cancer detection in the metachronous group.nnnRESULTSnOf 471 patients with brain metastases, 93 (20%) were included in the precocious group, 76 (16%) in the synchronous group, and 302 (64%) in the metachronous group. The precocious group tended to be symptomatic, show a low Karnofsky Performance Status, and have a large single tumor, infrequent extracranial metastases, and frequent tumor resection compared with the other 2 groups. There were no differences in overall survival from the detection of brain metastases among the 3 groups in univariate and multivariate analyses. Of 471 cases, 97 (21%) underwent surgeries. Among this surgical cohort, overall survival from surgery was significantly shorter in the precocious group than in the metachronous group (Pxa0= 0.039). After adjustment for age, sex, tumor size, primary cancer, and the Graded Prognostic Assessment score, the hazard ratio for metachronous metastases was 0.52 (confidence interval, 0.29-0.95; Pxa0= 0.035).nnnCONCLUSIONSnThe timing of brain metastasis diagnosis is not a modifiable factor but affects patient demographics and treatment strategies. In particular, the precocious group is a unique subset of brain metastases that require special consideration during clinical decision making.

A case report: C2 radiculopathy induced by neck flexion due to the cord compression of C2 segmental type vertebral artery relieved by microvascular decompression

Background: Decompression of an anomalous vertebral artery (VA) may effectively treat cervical myelopathy/radiculopathy due to resultant spinal cord or nerve compression. Here we report a case of C2 radiculopathy induced by neck flexion due to cord compression of the C2 segmental type VA relieved by microvascular decompression. Case Description: A 30-year-old female presented with left occipitalgia, sensory abnormalities in the left upper and lower extremities, and neck pain induced by neck flexion. The magnetic resonance imaging (MRI) revealed an abnormal flow void, confirming that the VA was compressing the spinal cord at the C1 level. Three-dimensional computed tomography (3D-CT) showed an anomalous course of the left VA, which entered the spinal canal between the axis and atlas. Microvascular decompression was performed by transposing the artery (e.g., anchoring it to the dura using PTEF): this effectively relieved cord compression. Conclusion: An anomalous VA rarely causes cervical radiculopathy induced by neck flexion. When it occurs, microvascular decompression effectively relieves pressure resulting in a resolution of symptoms.

Indications for salvage surgery during treatment for intracranial germ cell tumors

This study retrospectively reviewed our single institute experience to clarify the optimal indication and timing of salvage surgery. Retrospective analysis of 159 consecutive cases with germ cell tumors identified 20 cases with salvage surgery. These cases were classified based on the radiological response to neoadjuvant treatment before salvage surgery into increase (growing group, five cases), no change (stable group, seven cases), and decrease (shrinkage group, eight cases) in tumor size. Changes in tumor markers, histological findings, and the pattern of failure after salvage surgery were reviewed. Growing teratoma syndrome (GTS) is defined as enlargement of tumor consisting of mature teratoma after chemotherapy with normalization of tumor markers. In growing group, two cases presented GTS, whereas other three cases did not fulfill the criteria for GTS. All cases in stable and shrinkage group had elevated levels of tumor markers at presentation and decreased levels after neoadjuvant treatment. Histologically, sparse components of mature teratoma with extensive fibrosis were found in cases with GTS and seven of eight cases in shrinkage group, whereas mature teratoma without fibrosis was found in six of seven cases in stable group. Six cases recurred after salvage surgery. We identified three factors as risks for recurrence after salvage surgery, as follows: (1) growing lesion which did not fulfill the criteria for GTS, (2) non-normalized level of tumor marker before salvage surgery, and (3) residual germinoma component. In conclusion, salvage surgery is recommended for patients with GTS, or with normalized tumor markers in stable or shrinkage group.