Mikhail Chernov, Yoshihiro Muragaki and Hiroshi Iseki
Mikhail Chernov, Yoshihiro Muragaki and Hiroshi Iseki
Fujun Liu, Wei Chen and Jing Chen
Takahiro Shioyama, Yoshihiro Muragaki, Takashi Maruyama, Takashi Komori and Hiroshi Iseki
Intraoperative histopathological investigation plays an important role during surgery for gliomas. To facilitate the rapid characterization of resected tissue, an original technique of intraoperative flow cytometry (iFC) was established. The objective in this study was evaluation of this technique's efficacy for rapidly determining tumor presence in the surgical biopsy sample and WHO histopathological grade of the neoplasm.
In total, 328 separate biopsy specimens obtained during the resection of 81 intracranial gliomas were analyzed with iFC. The evaluated malignancy index (MI) was defined as the ratio of the number of cells with greater than normal DNA content to the total number of cells. The duration of iFC in all cases was approximately 10 minutes. Each sample was additionally investigated histopathologically on frozen and permanent formalin-fixed paraffin-embedded tissue sections. The latter process was used as a “gold standard” control for evaluation of the diagnostic efficacy of iFC analysis.
The MI differed significantly between neoplastic and perilesional brain tissue (25.3% ± 22.0% vs 4.6% ± 2.6%, p < 0.01). Receiver operating characteristic curve analysis revealed a corresponding area under the curve value of 0.941. The optimal cutoff level of the MI for identification of tumor in the biopsy specimen was 6.8%, which provided 0.88 sensitivity, 0.88 specificity, 0.97 positive predictive value, 0.60 negative predictive value, and 0.88 diagnostic accuracy. Additionally, the MI showed a significant association with WHO histopathological grades of glioma (p < 0.01), but its values in Grade II, III, and IV tumors overlapped prominently and were on average 13.3% ± 11.0%, 35.0% ± 21.8%, and 46.6% ± 23.1%, respectively.
Results of this study demonstrate that iFC with the determination of the MI may be feasible for rapidly determining glioma presence in a surgical biopsy sample.
Hiroki Hori, Toshio Yamaguchi, Yoshiyuki Konishi, Takaomi Taira and Yoshihiro Muragaki
This study evaluated changes of fractional anisotropy (FA) in the ventral intermediate nucleus (VIM) of the thalamus after transcranial MR-guided focused ultrasound (TcMRgFUS) thalamotomy and their associations with clinical outcome.
Clinical and radiological data of 12 patients with medically refractory essential tremor (mean age 76.5 years) who underwent TcMRgFUS thalamotomy with VIM targeting were analyzed retrospectively. The Clinical Rating Scale for Tremor (CRST) score was calculated before and at 1 year after treatment. Measurements of the relative FA (rFA) values, defined as ratio of the FA value in the targeted VIM to the FA value in the contralateral VIM, were performed before thalamotomy, and 1 day and 1 year thereafter.
TcMRgFUS thalamotomy was well tolerated and no long-term complications were noted. At 1-year follow-up, 8 patients demonstrated relief of tremor (improvement group), whereas in 4 others persistent tremor was noted (recurrence group). In the entire cohort, mean rFA values in the targeted VIM before treatment, and at 1 day and 1 year after treatment, were 1.12 ± 0.15, 0.44 ± 0.13, and 0.82 ± 0.22, respectively (p < 0.001). rFA values were consistently higher in the recurrence group compared with the improvement group, and the difference reached statistical significance at 1 day (p < 0.05) and 1 year (p < 0.01) after treatment. There was a statistically significant (p < 0.01) positive correlation between rFA values in the targeted VIM at 1 day after thalamotomy and CRST score at 1 year after treatment. Receiver operating characteristic curve analysis revealed that the optimal cutoff value of rFA at 1 day after thalamotomy for prediction of symptomatic improvement at 1-year follow-up is 0.54.
TcMRgFUS thalamotomy results in significant decrease of rFA in the targeted VIM, at both 1 day and 1 year after treatment. Relative FA values at 1 day after treatment showed significant correlation with CRST score at 1-year follow-up. Therefore, FA may be considered a possible imaging biomarker for early prediction of clinical outcome after TcMRgFUS thalamotomy for essential tremor.
Kotoe Kamata, Satoshi Hagihira, Takashi Maruyama, Yoshihiro Muragaki and Makoto Ozaki
Tomokazu Takakura, Yoshihiro Muragaki, Manabu Tamura, Takashi Maruyama, Masayuki Nitta, Chiharu Niki and Takakazu Kawamata
The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits.
Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (DHS-L) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between DHS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change.
From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (DHS-L < 10 mm, n = 6), the nonadjacent group (DHS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between DHS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively).
Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer DHS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.
Our failure to advance new treatments for glioma to market
John H. Sampson, Thomas J. Kaminski and Kevin A. Schulman
Yu Fujii, Yoshihiro Muragaki, Takashi Maruyama, Masayuki Nitta, Taiichi Saito, Soko Ikuta, Hiroshi Iseki, Kazuhiro Hongo and Takakazu Kawamata
WHO Grade III gliomas are relatively rare and treated with multiple modalities such as surgery, chemotherapy, and radiotherapy. The impact of the extent of resection (EOR) on improving survival in patients with this tumor type is unclear. Moreover, because of the heterogeneous radiological appearance of Grade III gliomas, the MRI sequence that best correlates with tumor volume is unknown. In the present retrospective study, the authors evaluated the prognostic significance of EOR.
Clinical and radiological data from 122 patients with newly diagnosed WHO Grade III gliomas who had undergone intraoperative MRI–guided resection at a single institution between March 2000 and December 2011 were analyzed retrospectively. Patients were divided into 2 groups by histological subtype: 81 patients had anaplastic astrocytoma (AA) or anaplastic oligoastrocytoma (AOA), and 41 patients had anaplastic oligodendroglioma (AO). EOR was calculated using pre- and postoperative T2-weighted and contrast-enhanced T1-weighted MR images. Univariate and multivariate analyses were performed to evaluate the prognostic significance of EOR on overall survival (OS).
The 5-, 8-, and 10-year OS rates for all patients were 74.28%, 70.59%, and 65.88%, respectively. The 5- and 8-year OS rates for patients with AA and AOA were 72.2% and 67.2%, respectively, and the 10-year OS rate was 62.0%. On the other hand, the 5- and 8-year OS rates for patients with AO were 79.0% and 79.0%; the 10-year OS rate is not yet available. The median pre- and postoperative T2-weighted high–signal intensity volumes were 56.1 cm3 (range 1.3–268 cm3) and 5.9 cm3 (range 0–180 cm3), respectively. The median EOR of T2-weighted high–signal intensity lesions (T2-EOR) and contrast-enhanced T1-weighted lesions were 88.8% (range 0.3%–100%) and 100% (range 34.0%–100%), respectively. A significant survival advantage was associated with resection of 53% or more of the preoperative T2-weighted high–signal intensity volume in patients with AA and AOA, but not in patients with AO. Univariate analysis showed that preoperative Karnofsky Performance Scale score (p = 0.0019), isocitrate dehydrogenase 1 (IDH1) mutation (p = 0.0008), and T2-EOR (p = 0.0208) were significant prognostic factors for survival in patients with AA and AOA. Multivariate analysis demonstrated that T2-EOR (HR 3.28; 95% CI 1.22–8.81; p = 0.0192) and IDH1 mutation (HR 3.90; 95% CI 1.53–10.75; p = 0.0044) were predictive of survival in patients with AA and AOA.
T2-EOR was one of the most important prognostic factors for patients with AA and AOA. A significant survival advantage was associated with resection of 53% or more of the preoperative T2-weighted high–signal intensity volume in patients with AA and AOA.