World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: (1) GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; (2) after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; (3) although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; (4) comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45 to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and (7) poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored.
Nonenhancing intrinsic brain tumors have been empirically treated with a strategy that has been adopted for World Health Organization (WHO) grade II gliomas (low-grade gliomas: LGGs), even though small parts of the tumors might have been diagnosed as WHO grade III gliomas after surgery. However, the best surgical strategy for nonenhancing gliomas, including LGGs, is still debatable. LGGs have the following features: slow growth, high possibility of histologically malignant transformation, and no clear border between the tumor and adjacent normal brain. We retrospectively examined 26 consecutive patients with nonenhancing gliomas who were surgically treated at Kanazawa University Hospital between January 2006 and May 2012, with special reference to functional reorganization, extent of resection (EOR), and functional mapping during awake surgery. These categories are closely related with the features of LGG, i.e. functional reorganization due to slow-growing nature, EOR with related malignant transformation, and functional mapping for delineating the unclear tumor border. Finally, we discuss surgical strategies for slow-growing gliomas that are represented by LGGs and nonenhancing gliomas. In conclusion, slow-growing gliomas tend to undergo functional reorganization, and the functional reorganization affects the presurgical evaluation for resectability based on tumor location related to eloquence. In the clinical setting, to definitely identify the reorganized functional regions, awake surgery is recommended. Therefore, awake surgery could increase the extent of the resection of the tumor without deficits, resulting in the delay of malignant transformation and increase in overall survival.
The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm3 (range 0.7-162 cm3) and 1.7 cm3 (range 0-135.7 cm3) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.
We retrospectively analyzed 15 years experience of awake surgeries for neuroepithelial tumors in Tohoku University. Awake surgeries mostly for language mapping were performed for 42 of 681 newly diagnosed cases (6.2%) and 59 of 985 surgeries including for recurrence (6.0%). When the same histologies and locations as cases resected under awake condition are selected from the parent population treated by radical resection, awake surgeries were most frequently performed for 14 of 55 newly diagnosed cases (25.5%) and 14 of 62 surgeries (22.6%) with grade II gliomas. In the results, 8 of 59 surgeries (13.6%) could not achieve complete language monitoring until the final stage of tumor resection, considered as failed awake surgery. Gross total resection was accomplished in 20 of 42 newly diagnosed cases (47.6%) and 32 of 59 surgeries (54.2%). Mortality rate was 0%. Late severe deficits were observed in 2 of 42 newly diagnosed cases (4.8%) and 3 of 59 surgeries (5.1%). Negative language mapping cases did not suffer severe deficits in both early and late stages. In contrast, high incidence of severe deficits, 3 as early and 2 as late of 8 cases, were identified with failed awake surgery. The overall survival of patients treated by awake surgery compared favorably with those treated without stimulation mapping and with stimulation mapping under general anesthesia. Awake surgery may contribute to improve the outcome of gliomas near eloquent areas by maximizing the tumor resection and minimizing the surgical morbidity.
The independent risk factors for venous thromboembolism (VTE) were investigated in patients with neuroepithelial tumor to establish a risk score for VTE. Our prospective study enrolled 395 hospitalized cases with neuroepithelial tumors. All cases underwent measurement of serum D-dimer concentration and neurological examination on admission. Serum D-dimer concentration was measured on days 1, 3, and 7 after surgery and weekly during follow up in patients who underwent surgery, and once a week during follow up in patients without surgery. Fourteen clinical parameters were evaluated as indicators of VTE, and among them, age, body-mass index, chemotherapy, radiation therapy, corticosteroid usage, pretreatment serum D-dimer concentration, paresis of the lower extremity (manual muscle test: MMT), performance status, and World Health Organization grade of the tumor achieved statistical significance. Multivariable logistic regression analysis demonstrated age >65 years, corticosteroid usage, paresis of the lower extremity, and serum D-dimer concentration over 1.0 mg/dl were independent factors. Total risk score was defined as the total of the scores for risk factors assigned based on the adjusted odds ratio: pretreatment serum D-dimer concentration over 1.0 mg/dl (2 points), and age over 65 years old, paresis of the lower extremity of MMT ≤2, and corticosteroid usage (1 point each). Rates of VTE were 2.0% in the low risk (total score 0 or 1), 14.8% in the intermediate risk (total score 2 or 3), and 51.9% in the high risk groups (total score = 4 or 5). This pretreatment risk score for VTE might be useful to identify patients who would benefit from thromboprophylaxis.
Clinically, recurrent glioblastoma multiforme (GBM) is often associated with communicating hydrocephalus. We hypothesized that there are specific magnetic resonance (MR) imaging findings at the diagnosis of recurrent GBM that predict subsequent hydrocephalus. Various clinical characteristics were investigated including outcome and MR imaging findings in 12 patients with recurrent GBM followed by hydrocephalus (Hydro group) and 21 patients with recurrent GBM without hydrocephalus (Non-hydro group). Patient age and presence of communicating hydrocephalus were significantly associated with poor outcome. Median survival with recurrent GBM was longer in the Non-hydro group than in the Hydro group. Low Karnofsky performance status (KPS) and poor recursive partitioning analysis (RPA) class (RPA class 3, 5, 6, or 7) at the diagnosis of recurrent GBM were associated with the presence of hydrocephalus. The incidence of leptomeningeal dissemination after recurrent GBM was higher in the Hydro group than in the Non-hydro group. Evans index and fractional anisotropy value showed no difference at the diagnosis of recurrent GBM, but some MR imaging findings indicated that lesion attached to the basal cistern and/or ventricle was closely associated with subsequent hydrocephalus. We recommend careful monitoring of the ventricle size and leptomeningeal dissemination, especially in patients with low KPS and/or poor RPA class, if MR imaging indicates that the lesion is attached to the basal cistern and/or ventricle at recurrence of GBM.
The principles of echo-shifting with a train of observations (PRESTO) magnetic resonance (MR) imaging technique employs an MR sequence that sensitively detects susceptibility changes in the brain. The effectiveness of PRESTO MR imaging was examined for distinguishing between cerebellopontine angle (CPA) schwannomas and meningiomas in 24 patients with CPA tumors, 12 with vestibular schwannomas, and 12 with meningiomas. Histopathological study of surgical specimens showed that 11 of the 12 schwannomas contained hemosiderin deposits and all had microhemorrhages. One meningioma contained hemosiderin deposits and two involved microhemorrhages. Abnormal vessel proliferation, and dilated and thrombosed vessels were observed in all schwannomas and in 4 meningiomas. In addition to MR imaging with all basic sequences, PRESTO MR imaging and computed tomography were performed. PRESTO imaging showed significantly more schwannomas (n = 12) than meningiomas (n = 2) exhibited intratumoral spotty signal voids which were isointense to air in the mastoid air cells (p < 0.001). These spotty signal voids were significantly associated with histopathologically demonstrated hemosiderin deposits (p < 0.001), microhemorrhages (p < 0.01), and abnormal vessels (p < 0.04). The visualization of spotty signal voids on PRESTO images is useful to distinguish schwannomas from meningiomas.
The present detailed radiological study investigated the relationship between petroclival meningiomas and petrosal veins with contrast-enhanced (CE) principles of echo-shifting with a train of observations (PRESTO) imaging to assess the potential contribution of the findings to the surgical strategy. Fourteen patients (13 women and 1 man) with unilateral petroclival meningiomas underwent microsurgical resection at Osaka City University Hospital between April 2009 and February 2011. Preoperatively, patients were examined using computed tomography (CT) and magnetic resonance (MR) imaging, including CE PRESTO imaging, focusing on the relationship between the tumor and the petrosal vein, and compared to the sensitivity of three-dimensional CT (3D-CT) venography or conventional MR imaging, including CE MR venography and constructive interference in steady-state (CISS) MR imaging. In 11 of 14 cases, we could identify the petrosal veins with intraoperative findings. In 10 of these 14 cases, the anatomical relationship between the tumor and the petrosal vein was detected preoperatively with CE PRESTO imaging, compared to 5 of 14 cases with 3D-CT venography, 5 of 14 cases with CE MR venography, and only 4 of 14 cases using CISS MR imaging. CE PRESTO imaging compares favorably to other approaches. There was no venous complication related to the surgery in any of the cases. CE PRESTO imaging is a non-invasive and useful method to assess the status of the petrosal vein in patients with petroclival meningiomas.
Increased signal intensity (SI) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images in the resection cavity is sometimes observed after partial resection of gliomas. SI in the resection cavity of 44 high-grade gliomas was retrospectively investigated. Twelve of 35 patients with progressive disease (PD) showed SI increase in the resection cavity, and SI increase preceded PD in 6 of these 12 patients. None of nine patients without PD showed SI increase during the follow-up period. The analysis of SI on FLAIR images in the resection cavity had a specificity of 100% and a sensitivity of 34%. Higher sensitivity was found in grade IV tumors than in grade III tumors. SI increase is thus considered as a potent highly specific hallmark for subsequent or coincident tumor progression, which is clinically useful since MR imaging is easily performed during routine clinical examinations.
The usefulness of 1.5-T high-field intraoperative magnetic resonance (iMR) imaging during transsphenoidal surgery for functioning pituitary adenomas was retrospectively evaluated based on long-term endocrine remission from the records of 14 patients who underwent transsphenoidal surgery with iMR imaging for functioning pituitary microadenomas and small adenomas located in the intrasellar region. The maximum tumor diameter was 9.3 ± 2.6 mm. Patients were diagnosed with acromegaly (n = 7), prolactinoma (n = 4), and Cushing's disease (n = 3). If iMR imaging detected tumor remnants after resection, the resection cavity was reexamined and further resection was performed. Postoperative endocrine follow-up period was mean 33.7 ± 13.3 months. Tumor remnants were detected after the first resection in seven patients. Further resection was performed in five of these patients, and three achieved long-term endocrine remission. As a result, the overall long-term endocrine remission rate was 78.5% (11/14), instead of the 57.1% (8/14) that would be expected if iMR imaging had not been performed. Long-term endocrine remission had a tendency to be associated with the absence of tumor remnants on the final iMR images, but this was not significant (p = 0.09). Long-term endocrine remission was associated with presence of tumor remnants in the cavernous sinus on the final iMR images (p = 0.03). High-field iMR imaging is useful for depicting tumor remnants after resection, and increased the long-term endocrine remission rate for patients with functioning pituitary microadenomas and small adenomas.