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OBJECTIVE An autologous formalin-fixed tumor vaccine (AFTV) derived from resected glioblastoma (GBM) tissue can be used against unidentified tumor antigens. Thus, the authors conducted a multicenter double-blind phase IIb trial to investigate the efficacy of an AFTV. METHODS Eligible patients were adults with supratentorial GBMs, 16–75 years of age, with Karnofsky Performance Scale (KPS) scores ≥ 60%, and no long-term steroid administration. An AFTV comprising fixed paraffin-embedded tumor tissue with immune adjuvants or an identical placebo without fixed tumor tissue was injected intradermally over three courses before and after chemoradiotherapy. The primary and secondary end points were overall survival (OS), progression-free survival (PFS), and 3-year survival rate. RESULTS Sixty-three patients were enrolled. The average patient age was 61 years. The median KPS score was 80%, and the median resection rate was 95%. The full analysis set of 57 patients indicated no significant difference in OS (p = 0.64) for the AFTV group (median OS 25.6 months, 3-year OS rate 38%) compared with the placebo group (31.5 months and 41%, respectively) and no difference in PFS (median PFS 13.3 months in both groups, p = 0.98). For patients with imaging-based total tumor removal, the 3-year PFS rate was 81% in the AFTV group versus 46% in the placebo group (p = 0.067), whereas the 3-year OS rate was 80% versus 54% (p = 0.16), respectively. Similar results were obtained in the p53-negative subgroups. Severe adverse effects were not observed. CONCLUSIONS The AFTV may have potential effects in certain patient subgroups. A phase III study for patients with total tumor removal remains warranted to confirm these findings. Clinical trial registration no.: UMIN000010602 (UMIN Clinical Trials Registry)

Surgical site infections (SSIs) after neurosurgery are common in daily practice. Although numerous reports have described SSIs in neurosurgery, reports specific to gliomas are limited. This study aimed to investigate the relationship between SSIs and glioma treatment characteristics, such as reoperations, radiation therapy, and chemotherapy.We examined 1012 consecutive patients who underwent craniotomy for glioma between November 2013 and March 2022. SSIs were defined as infections requiring reoperation during the observation period, regardless of their location. We retrospectively analyzed SSIs and patient factors.During the observation period, SSIs occurred in 3.1% (31/1012). In the univariate analysis, three or more surgeries (P = 0.007) and radiation therapy (P = 0.03) were associated with SSIs, whereas intraoperative magnetic resonance imaging (MRI) was not significantly associated (P = 0.35). Three or more surgeries and radiation therapy were significantly correlated with each other (P .0001); therefore, they were analyzed separately in the multivariate analysis. Three or more surgeries were an independent factor triggering SSIs (P = 0.02); in contrast, radiation therapy was not an independent factor for SSIs (P = 0.07). Several SSIs localized in the skin occurred more than 1 year after surgery.Undergoing three or more surgeries for glioma is an independent risk factor for SSIs. Glioma SSIs can occur long after surgery. These results are considered characteristic of gliomas. We recommend careful long-term observation of patients at a high risk of SSIs.

Resection of the dominant side of gliomas extending to the frontal operculum has a high-risk of permanent language dysfunction. Here, we report recording cortico-cortical evoked potentials (CCEP) using only two 6-strand strip electrodes to monitor language-related fibers intraoperatively. We examined whether this simple procedure is useful for removing gliomas extending to the dominant side of frontal operculum. This study included five cases of glioma extending to the left frontal operculum. The frontal language area (FLA) was first identified by functional mapping during awake craniotomy. Next, a 6-strand strip electrode was placed just above the FLA, while on the temporal lobe side, an electrode was placed so as to slide parallel to the Sylvian fissure toward the posterior language area. Electrical stimulation was performed using the electrode on the frontal side, and CCEPs were measured from the electrode on the temporal side. CCEPs were detected in all cases. Immediately after surgery, all patients demonstrated language dysfunction to varying degrees. CCEP decreased up to 10% in one patient, who recovered language function after 24 months. CCEP decreased slightly up to 80% in one, and in the three other cases, CCEPs did not change. These four patients soon recovered language function within 2 weeks to 1 month. This study confirmed the utility of CCEP monitoring using only two 6-strand strip electrodes during one-step surgery. We believe this simple method helped in monitoring intraoperative language function and aided predicting its postoperative recovery, in patients with gliomas extending to the dominant side of frontal operculum.

OBJECTIVE Identification of the motor area during awake craniotomy is crucial for preservation of motor function when resecting gliomas located within or close to the motor area or the pyramidal tract. Nevertheless, sometimes the surgeon cannot identify the motor area during awake craniotomy. However, the factors that influence failure to identify the motor area have not been elucidated. The aim of this study was to assess whether tumor localization was correlated with a negative cortical response in motor mapping during awake craniotomy in patients with gliomas located within or close to the motor area or pyramidal tract. METHODS Between April 2000 and May 2019 at Tokyo Women’s Medical University, awake craniotomy was performed to preserve motor function in 137 patients with supratentorial glioma. Ninety-one of these patients underwent intraoperative cortical motor mapping for a primary glioma located within or close to the motor area or pyramidal tract and were enrolled in the study. MRI was used to evaluate whether or not the tumors were localized to or involved the precentral gyrus. The authors performed motor functional mapping with electrical stimulation during awake craniotomy and evaluated the correlation between identification of the motor area and various clinical characteristics, including localization to the precentral gyrus. RESULTS Thirty-four of the 91 patients had tumors that were localized to the precentral gyrus. The mean extent of resection was 89.4%. Univariate analyses revealed that identification of the motor area correlated significantly with age and localization to the precentral gyrus. Multivariate analyses showed that older age (≥ 45 years), larger tumor volume (> 35.5 cm3), and localization to the precentral gyrus were significantly correlated with failure to identify the motor area (p = 0.0021, 0.0484, and 0.0015, respectively). Localization to the precentral gyrus showed the highest odds ratio (14.135) of all regressors. CONCLUSIONS Identification of the motor area can be difficult when a supratentorial glioma is localized to the precentral gyrus. The authors’ findings are important when performing awake craniotomy for glioma located within or close to the motor area or the pyramidal tract. A combination of transcortical motor evoked potential monitoring and awake craniotomy including subcortical motor mapping may be needed for removal of gliomas showing negative responses in the motor area to preserve the motor-related subcortical fibers.

Glioma patients were frequently associated with mucosal thickening of the maxillary sinus (MTMS), which reflects mucosal inflammation. We suspected that MTMS is associated with impaired mucosal immune response and correlated with dysfunction in the anti-tumor immune response in diffuse glioma patients. Therefore, the aim of this study was to determine whether the occurrence of diffuse glioma is correlated with MTMS compared to meningioma and control groups. Furthermore, we investigated whether MTMS is associated with overall survival (OS) in glioblastoma (GBM) patients. This study included 343 patients with newly diagnosed diffuse gliomas and 218 patients with meningioma treated at our institution between 2015 and 2018. As control, 201 patients with headache who did not have an intracranial organic lesion were included. Using three-axis MR images, we evaluated the incidence of MTMS in all patients. Additionally, we investigated the relationship between MTMS and OS. The incidence of MTMS in patients with diffuse glioma was significantly higher than that in the meningioma (p < .0001) and control groups (p < .0001). In 128 patients with GBM, MTMS status correlated significantly with OS (p = .0064). We revealed that the incidence of MTMS is significantly associated with patients with diffuse glioma. This suggests that MTMS is indirectly involved in the occurrence of diffuse gliomas. Furthermore, the presence of MTMS correlated significantly with shorter OS in GBM patients, indicating that MTMS is involved in suppression of anti-tumor immune response. Preoperative recognition of MTMS might be useful for improving the clinical management of GBM patients.

Introduction Glioblastoma has the poorest prognosis among brain tumors, and most cases recur. On the other hand, evidence of prognosis improvement by maximal surgical removal of the tumor is being established, and in recent years, new treatments such as temozolomide (2006), photodynamic therapy (2014), and TTF therapy (2018) were approved by insurance. and patient outcome has improved. In addition, molecular targeted therapy (bevacizumab approved in 2011) and immunotherapy are also used in clinical practice. In this study, we retrospectively analyzed the long-term treatment results of newly diagnosed glioblastoma cases treated at our facility, the correlation with the resection rate, and the treatment results by age and treatment method. Methods We retrospectively analyzed the clinical characteristics, resection rate, and treatment outcomes of adult patients with primary supratentorial glioblastoma who underwent surgery and treatment at our institution during the 20-year period from 2001 to 2021. Results 493 cases, median age 58 years (18-85 years), 293 males and 200 females. The median and mean contrast-enhanced lesion resection rates in resection cases were 98% and 96.6%, respectively. Median PFS and OS for all patients (including biopsies) were 9.4 months and 22.7 months, respectively. The median OS for each age was 12.9 months, 22.9 months, 23 months, and 31.1 months when analyzed separately for 2001-2006, 2007-2010, 2011-2015, and 2016-2021 before TMZ. (p Conclusion Treatment results for glioblastoma improve with age, and the time has come when we can aim for a 5-year survival rate of 50% by combining a high resection rate with multidisciplinary therapy including intraoperative MRI, PDT, AFTV and TTF.

OBJECTIVEResection of gliomas in the precentral gyrus carries a risk of severe motor dysfunction. To prevent permanent, severe postoperative motor dysfunction, reliable intraoperative predictors of postoperative function are required. Since 2005, the authors have removed gliomas in the precentral gyrus with combined functional mapping and estimation of intraoperative voluntary movement (IVM) during awake craniotomy and transcortical motor evoked potentials (MEPs). The purpose of the current study was to evaluate whether intraoperative findings of combined monitoring of IVM during awake craniotomy and transcortical MEP monitoring were useful for predicting postoperative motor function of patients with gliomas in the precentral gyrus.METHODSThe current study included 30 patients who underwent resection of precentral gyrus gliomas during awake craniotomy from April 2000 to January 2018. All tumors were removed with monitoring of IVM during awake craniotomy and transcortical MEPs. Postoperative motor function was classified as stable or declined, with the extent of decline categorized as mild, moderate, or severe. We defined moderate and severe deficits were those that hindered daily life.RESULTSIn 28 of 30 cases, available waveforms were obtained with transcortical MEPs. The mean extent of resection (EOR) was 93%. Relative to preoperative status, motor function 6 months after surgery was considered stable in 20 patients and was considered to show mild decline in 7, moderate decline in 2, and severe decline in 1. Motor function 6 months after surgery was significantly correlated with IVM (p = 0.0096), changes in transcortical MEPs (decline ≤ or > 50%) (p = 0.0163), EOR, and ischemic lesions on postoperative MRI. Six patients with no change in IVM showed stable motor function 6 months after surgery. Only 2 patients with a decline in IVM and a decline in MEPs ≤ 50% had a decline in motor function 6 months after surgery (18%; 2/11 patients), whereas 11 patients with a decline in IVM and a decline in MEPs > 50% had such a decline in motor function (73%; 8/11 patients) including 2 patients with moderate and 1 with severe deficits. Three patients with moderate or severe motor deficits showed the lowest MEP values (< 100 µV).CONCLUSIONSCombined judgment from monitoring of IVM during awake craniotomy and transcortical MEPs is useful for predicting postoperative motor function during removal of gliomas in the precentral gyrus. Maximum resection was achieved with an acceptable morbidity rate. Thus, these tumors should not be considered unresectable.

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.

Purpose Thalamic diffuse glioma is classified as WHO grade 4 as Diffuse midline glioma, H3K27M mutation if H3K27M mutation was found regardless of its histological findings, but the significance of H3K27M mutation is not clear compared with pediatric cases. We aimed to find genetic prognostic factors in adult thalamic diffuse gliomas. METHODS Pathological diagnosis, genetic abnormalities, and clinical course of adult newly diagnosed thalamic gliomas diagnosed and treated at our institution from July 2007 to March 2020 were retrospectively analyzed. RESULTS The number of cases was 41 (24 males, 17 females), median age was 47 years (20-75 years). Tumor localization was 20 cases on the left, 14 cases on the right, and 7 cases on both sides. The pathological diagnosis was GBM 15 cases, DMG 15 cases, AA-IDH WT 7 cases, DA-IDH WT 4 cases, all of which were IDH wild type, and none of them had IDH mutation and 1p/19q co-deletion. H3K27M mutations were found in 15 cases and TERT promoter mutations were found in 12 cases, both of which were completely mutually exclusive. Tumor resection and biopsy was performed in 33 and 8 cases, respectively, and the median removal rate was 95% for those who underwent tumor resection. The median PFS and OS of all cases were 14.3 months and 38 months, respectively, and the median OS by pathological diagnosis was GBM 12.4 months, DMG 47.4 months, AA-IDH WT 37.3 months, DA-IDH WT not reached. The median OS in the H3K27M mutant group (47.4 months) was significantly better (p=0.02) than that in the TERT promoter mutation group (13.5 months). CONCLUSION There was no IDH mutation in adult thalamic gliomas, the H3K27M mutation and the TERT promoter mutation were mutually exclusive. The H3K27M mutation was not a prognostic factor, but the TERT promoter mutation was the strongest prognostic factor.

Background In the course of treatment of malignant gliomas, the appearance of contrast-enhanced lesions and surrounding T2/FLAIR high-signal after treatment is often experienced. There is no modality that can reliably diagnose whether the lesion is a recurrence or a response to treatment, including radiation necrosis. Furthermore, the choice of treatment modality is often difficult, such as reexcision, stereotactic irradiation, Avastin. Very few reports have examined the relationship between the irradiation field and histology. Methods Thirty-seven lesions in 30 patients who underwent repeat resection of malignant gliomas at our institution from October 2019 to December 2021 were analyzed retrospectively. Based on postoperative pathology, the patients were classified into two groups: recurrence group and radiation necrosis group.In each group, age, gender, histology at initial surgery, IDH status, radiation and chemotherapy, TNR of Methionine-PET, and the number of days after the end of treatment until the appearance of contrast lesions were considered. Results The recurrence group consisted of 20 patients with 26 lesions, mean age 48 years, male/female = 13/7, pathology was GBM 13, DA 1, AA 3, AO 2, AE 1, TNR 3.33 (1.41-6.32), and time to contrast appearance 547 (14-2427) days. PDT in combination with initial surgery was seen in 9 patients.The necrosis group consisted of 10 patients with 11 lesions, mean age 47 years, male/female = 4/6, pathology GBM 5, AA 2, AO 1, PXA 2. TNR 2.51 (1.20-3.75), 318 (24-678) days to contrast appearance, 2 patients had PDT. Conclusions Radiation necrosis tended to have lower TNR and shorter time to lesion appearance than recurrence, but no significant difference was observed. Improvement of diagnostic accuracy with modalities is desirable, and unnecessary irradiation is highly likely to contribute to ADL deterioration such as leukoencephalopathy and higher functional impairment.

Purpose Intraoperative magnetic resonance imaging (MRI) update navigation is performed in all cases to preserve neurological function and remove the tumor as much as possible, and to prevent recurrence and improve prognosis. And under awake craniotomy, we supported operators by integrating preoperative functional images with intraoperative MRI. We report our usefulness of image superimposition between medium magnetic field intraoperative MRI and preoperative position emission tomography (PET) and preoperative diffusion tensor imaging (DTI) color-map. Method Of more than 2,200 cases using intraoperative MRI since 2000, 58 preoperative PET (57 methionine and 1 FDG nuclides) superimposed cases (32 left-sided, 35 males, 15 under awake craniotomy, mean 44.8 y.o.) were evaluated. The tumor was located to 34 frontal-, 12 temporal-, 10 parietal lobes, 1 insular gyrus, 1 thalamus. Color-map image superimposition of preoperative DTI (3T, 6-axis application) anisotropic indices in 12 cases (localized in 8 frontal-, 2 insular-, 2 parietal lobes, 7 left-sided, 7 females, mean 35 y.o.). Neurophysiological monitoring was combined (5 under general, 7 awake anesthesia). Results The preoperative TN ratio was 3.8 (in 57 methionine-PET cases), and pathological results (Grade 3-4 in 15-31 cases respectively, out of 54 cases) were used for reliable and preferential removal of sites with higher malignancy and recurrence-prone sites. Recurrent cases (41/58) had altered brain structures that were too difficult to identify without the navigation. In the DTI cases, intraoperative MRI, DTI color-map, and microscopic surgical images were displayed on one screen, and white matter tracts information as a reference is quickly conveyed to operators, and helped to reduce perioperative neurological complications. Conclusion Co-registering an effective superimposition of medium magnetic field intraoperative MRI with high positional accuracy, and preoperative PET- and DTI- images according to the patient's characteristics is currently the most practical navigation application method for intraoperative prediction of important functional information.

Introduction Acquisition of somatic mutations is essential for the development of malignant tumors such as diffuse gliomas. Recent single-cell analyses have pointed out the importance of somatic mosaicism in the pathogenesis of cancer. Here we report a case of IDH (isocitrate dehydrogenase)-mutant astrocytoma that has relapsed after intensive chemoradiation with somatic mosaicism for the IDH1 R132H mutation. Clinical and Pathological Findings A 36-year-old male presented with epileptic symptoms and a mass lesion in the right frontal lobe. A needle biopsy demonstrated IDH-mutant astrocytoma (grade 2). At the age of 41, relapsed tumor was completely resected, and the tumor cells were diffusely positive for IDH1 R132H with grade 4 morphology. Chemoradiotherapy (PAV + IMRT 60Gy/30fr) was added, but contrast-enhanced lesions reappeared 5 months after the initial surgery. The re-excised specimen was grade 4 astrocytoma, and the number of IDH1 R132H-positive tumor cells was very small compared to the total number of tumor cells, suggesting somatic mosaicism for IDH mutations. Conclusion It is imperative to clarify the induction mechanism and significance of somatic cell mosaicism in cancer, and molecular genetic assessment with sequencing and digital PCR would be necessary in addition to immunostaining for accurate molecular diagnoses of the brain tumors.

INTRODUCTION Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. METHODS To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery of maximal resection with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery of maximal resection alone (control group). RESULTS The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. PDT was well tolerated by all patients and in no case did treatment-related severe adverse effects. There was also no significant difference in TS accumulation in the tumor between these two groups. CONCLUSION According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.

BACKGROUND Surgical site infection(SSI) in neurosurgery can increase mortality and worsen functional outcome. There are few reports on risk factors for SSI in glioma surgery. In this study, we investigated the risk factors for SSI in glioma surgery at our institution. METHODS We included 1013 patients with gliomas who underwent craniotomy between November 2013 and March 2022 at our institution. SSI was defined as requiring surgical treatment. Various factors including age, gender, number of operations, prior radiology, prior chemotherapy, use of intraoperative MRI, operation time, tumor WHO grade were investigated. RESULTS Among 1013 craniotomies, 31 (3.06%) cases of SSI required surgical procedure. In univariate analysis, the most significant factors were multiple prior craniotomy (p = 0.0067) and prior radiation therapy ( p = 0.0286). Among these factors, multivariate analysis revealed the number of surgeries ( p = 0.0151) as a significant independent factor for infection.Discussion and CONCLUSION Patients with gliomas often requires multiple craniotomy due to tumor recurrence. Although there have been reported the reoperation is an independent risk factor for postoperative infection, the is the first time that a specific number of prior surgeries ( 2 or more) has been reported. Radiotherapy is said to cause skin damage at a threshold of 10 Gy or less. Since radiation therapy for gliomas is given a dose of 50 Gy or more and irradiated scalp causes radiation dermatitis, and patients who have undergone prior radiotherapy must be carefully monitored.

INTRODUCTION Glioblastoma has the worst prognosis of brain tumors. Evidence for improving prognosis by maximal tumor removal is being established, and in recent years, new treatments such as photodynamic therapy (PDT, 2014 in Japan), and TTF therapy (2018) have been approved, the treatment results are improving. In principle, our facility performs maximum tumor removal using intraoperative MRI (iMRI) follow by the standard chemoradiation. Intraoperative PDT and autologous tumor vaccine (AFTV) will be given to desired patients. We retrospectively analyzed the long-term clinical results of the patients with newly diagnosed glioblastoma who underwent surgical treatment at our facility, and the treatment results by era and treatment method. METHODS The clinical features, extent of removal (EOR), OS and PFS of the adult patients with newly diagnosed glioblastoma treated from 2001 to 2021 were analyzed retrospectively. Clinical results of those patients who received PDT and AFTV treatment was also investigated. RESULTS The number of cases was 493, median age 58 years (18-85 years), 293 males, 200 females. The median and average EOR of contrast-enhanced lesions were 98% and 96.6%, respectively. The median PFS and OS of all cases (including biopsy) were 9.4 months and 22.7 months, respectively. When the cases were analyzed separately for 2001-2006 (before TMZ), 2007-2010, 2011-2015, and 2016-2021, the median OS for each age group was 12.9 months, 22.9 months, 23 months, and 31.1 months. The treatment results improved with age ( p < 0.0001). In particular, the median OS of 23 cases treated with PDT and AFTV was 63.1 months. The efficacy of AFTV for newly diagnosed glioblastoma is currently being verified in a multicenter Investigator-led clinical trial. CONCLUSION The treatment results for glioblastoma have improved over the years. The combination of maximal tumor removal using iMRI, PDT and AFTV may aim for a 5-year survival rate of 50%.

Introduction: Awake craniotomy (AC) with intraoperative mapping is the best approach to preserve neurological function for glioma surgery in eloquent or near eloquent areas, but whether AC improves the extent of resection (EOR) is controversial. Furthermore, there is less evidence of improved overall survival (OS) in glioma patients. This study aimed to compare the long-term clinical outcomes of glioma resection under AC with those under general anesthesia (GA).Methods: Data of 335 patients who underwent surgery with intraoperative magnetic resonance imaging for newly diagnosed gliomas of World Health Organization (WHO) grades II-IV between 2000 and 2013 were reviewed. EOR and OS were quantitatively compared between the AC and GA groups after 1:1 propensity score matching. The two groups were matched for age, preoperative Karnofsky performance status, tumor location, and pathology based on the WHO 2007 classification.Results: After propensity score matching, 91 pairs were obtained. The median EOR were 96.1% (interquartile range [IQR] 7.3) and 97.4% (IQR 14.4) in the AC and GA groups, respectively (p=0.31). The median survival times were 163.3 months (95% confidence interval [CI] 77.9-248.7) and 143.5 months (95% CI 94.4-192.7) in the AC and GA groups, respectively (p=0.585).Conclusions: Even if the glioma was within or close to the eloquent area, AC was comparable with GA in terms of EOR and OS. In case of difficulties in randomizing patients with eloquent or near eloquent glioma, our propensity score-matched analysis provides retrospective evidence that AC can obtain EOR and OS equivalent to removing glioma under GA.

Professor Masahiro Nakajima and Assistant Professor Masayuki Nitta are collaborating on a project that focuses on the reconstruction of a system that utilises and manages agricultural irrigation water stocks through maintenance and innovation. Their focus for the project is Japanese communities.

OBJECTIVEIn this study on the effectiveness and safety of photodynamic therapy (PDT) using talaporfin sodium and a semiconductor laser, the long-term follow-up results of 11 patients with glioblastoma enrolled in the authors’ previous phase II clinical trial (March 2009–2012) and the clinical results of 19 consecutive patients with newly diagnosed glioblastoma prospectively enrolled in a postmarket surveillance (March 2014–December 2016) were analyzed and compared with those of 164 patients treated without PDT during the same period.METHODSThe main outcome measures were the median overall survival (OS) and progression-free survival (PFS) times. Moreover, the adverse events and radiological changes after PDT, as well as the patterns of recurrence, were analyzed and compared between the groups. Kaplan-Meier curves were created to assess the differences in OS and PFS between the groups. Univariate and multivariate analyses were performed to identify the prognostic factors, including PDT, among patients with newly diagnosed glioblastoma.RESULTSThe median PFS times of the PDT and control groups were 19.6 and 9.0 months, with 6-month PFS rates of 86.3% and 64.9%, respectively (p = 0.016). The median OS times were 27.4 and 22.1 months, with 1-year OS rates of 95.7% and 72.5%, respectively (p = 0.0327). Multivariate analyses found PDT, preoperative Karnofsky Performance Scale score, and IDH mutation to be significant independent prognostic factors for both OS and PFS. Eighteen of 30 patients in the PDT group experienced tumor recurrence, including local recurrence, distant recurrence, and dissemination in 10, 3, and 4 patients, respectively. Conversely, 141 of 164 patients in the control group experienced tumor recurrence, including 101 cases of local recurrence. The rate of local recurrence tended to be lower in the PDT group (p = 0.06).CONCLUSIONSThe results of the present study suggest that PDT with talaporfin sodium and a semiconductor laser provides excellent local control, with few adverse effects even in cases of multiple laser irradiations, as well as potential survival benefits for patients with newly diagnosed glioblastoma.

Tumor recurrence patterns after resection of intracranial low-grade gliomas (LGG) generally remain obscured. The objective of the present retrospective study was their multifaceted analysis, evaluation of associated factors, and assessment of impact on prognosis. Study group comprised 81 consecutive adult patients (46 men and 35 women; median age, 37 years) with recurrent diffuse astrocytomas (DA; 51 cases) and oligodendrogliomas (OD; 30 cases). The median length of follow-up after primary surgery was 6.7 years. Early (within 2 years after primary surgery) and non-early (> 2 years after primary surgery) recurrence was noted in 23 (28%) and 58 (72%) cases, respectively. Fast (≤ 6 months) and slow ( > 6 months) radiological progression of relapse was noted in 31 (38%) and 48 (59%) cases, respectively. Tumor recurrence was local and non-local in 71 (88%) and 10 (12%) cases, respectively. Recurrence patterns have differed in OD, IDH1-mutant DA, and IDH wild-type DA. Early onset, fast radiological progression, and non-local site of relapse had statistically significant negative impact on overall survival of patients and were often associated with malignant transformation of the tumor (38 cases). However, in subgroup with extent of resection ≥ 90% (56 cases) no differences in recurrence characteristics were found between 3 molecularly defined groups of LGG. Recurrence patterns after resection of LGG show significant variability, differ in distinct molecularly defined types of tumors, and demonstrate definitive impact on prognosis. Aggressive resection at the time of primary surgery may result in more favorable characteristics of recurrence at the time of its development.

Antiseizure drug (ASD)-induced skin rash remains the main side effect of seizure management in patients with glioma. New generations of ASDs, such as levetiracetam (LEV) and lacosamide (LCM) are associated with less frequent skin rashes than conventional ASDs. However, there are few reports regarding the incidence of skin rashes by LEV and LCM in patients with glioma. Therefore, the aim of this study was to investigate the incidence and risk factors of LEV- and LCM-associated skin rashes in patients with glioma. We compared the incidence of ASD-associated skin rash between 353 patients with glioma and 125 patients with meningioma, who received LEV or LCM and underwent surgery between 2017 and 2019 at our institution. Furthermore, to evaluate the association between potential risk factors and ASD-associated skin rashes, univariate and multivariate analyses were performed. The incidence of ASD-associated skin rash in patients with glioma was higher (11%) than in those with meningiomas (1.6%). The multivariate regression analysis showed that adjuvant treatment with radiotherapy (p = 0.023) and a history of drug allergy (p = 0.023) were significant risk factors for ASD-associated skin rash. The rate of ASD-related skin rashes in patients with glioma was also higher than the previously reported rates of 1-3% in patients with epilepsy. Our results indicate that adjuvant treatment with radiotherapy and a history of drug allergy correlated with a high incidence of ASD-related skin rashes in patients with patients who receive LEV and LCM. Patients with these two factors should be carefully checked for skin rashes.

OBJECTIVE The authors previously showed that combined evaluation of changes in intraoperative voluntary movement (IVM) during awake craniotomy and transcortical motor evoked potentials (MEPs) was useful for predicting postoperative motor function in 30 patients with precentral gyrus glioma. However, the validity of the previous report is limited to precentral gyrus gliomas. Therefore, the current study aimed to validate whether the combined findings of IVM during awake craniotomy and transcortical MEPs were useful for predicting postoperative motor function of patients with a glioma within or close to motor-related areas and not limited to the precentral gyrus. METHODS The authors included 95 patients with gliomas within or close to motor-related areas who were treated between April 2000 and May 2020. All tumors were resected with IVM monitoring during awake craniotomy and transcortical MEP monitoring. Postoperative motor function was classified into four categories: “no change” or “declined,” the latter of which was further categorization as “mild,” “moderate,” or “severe.” The authors defined moderate and severe deficits as those that impact daily life. RESULTS Motor function 6 months after surgery was classified as no change in 71 patients, mild in 18, moderate in 5, and severe in 1. Motor function at 6 months after surgery significantly correlated with IVM (p < 0.0001), transcortical MEPs (decline ≤ or > 50%) (p < 0.0001), age, preoperative motor dysfunction, extent of resection, and ischemic change on postoperative MRI. Thirty-two patients with no change in IVM showed no change in motor function at 6 months after surgery. Five of 34 patients (15%) with a decline in IVM and a decline in MEPs ≤ 50% had motor dysfunction with mild deficits 6 months after surgery. Furthermore, 19 of 23 patients (83%) with a decline in IVM and decline in MEPs > 50% had a decline in motor function, including 13 patients with mild, 5 with moderate, and 1 with severe deficits. Six patients with moderate or severe deficits had the lowest MEP values, at < 100 µV. CONCLUSIONS This study validated the utility of combined application of IVM during awake craniotomy and transcortical MEP monitoring to predict motor function at 6 months after surgery in patients with a glioma within or close to motor-related areas, not limited to the precentral gyrus. The authors also validated the usefulness of the cutoff value, 100 µV, in MEP monitoring.

INTRODUCTION It is useful to know the molecular subtype of lower-grade gliomas (LGG) when deciding on a treatment strategy. This study aims to diagnose this preoperatively. METHODS A deep learning model was developed to predict the 3-group molecular subtype using multimodal data including magnetic resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The performance was evaluated using leave-one-out cross validation with a dataset containing information from 217 LGG patients. RESULTS The model performed best when the dataset contained MRI, PET, and CT data. The model could predict the molecular subtype with an accuracy of 96.6% for the training dataset and 68.7% for the test dataset. The model achieved test accuracies of 58.5%, 60.4%, and 59.4% when the dataset contained only MRI, MRI and PET, and MRI and CT data, respectively. The conventional method used to predict mutations in the isocitrate dehydrogenase (IDH) gene and the codeletion of chromosome arms 1p and 19q (1p/19q) sequentially had an overall accuracy of 65.9%. This is 2.8 percent point lower than the proposed method, which predicts the 3-group molecular subtype directly. CONCLUSIONS AND FUTURE PERSPECTIVE A deep learning model was developed to diagnose the molecular subtype preoperatively based on multi-modality data in order to predict the 3-group classification directly. Cross-validation showed that the proposed model had an overall accuracy of 68.7% for the test dataset. This is the first model to double the expected value for a 3-group classification problem, when predicting the LGG molecular subtype. We plan to apply the techniques of heat map and/or segmentation for an increase in prediction accuracy.

In this report, the authors present the first case of adult brainstem pilocytic astrocytoma (PA) with the H3 K27M mutation. A 53-year-old man was incidentally found to have a 2.5-cm partially enhanced tumor in the tectum on MRI. The enhancement in the lesion increased over 3 years, and gross-total removal was performed via the occipital transtentorial approach. The resected tissue indicated PA, WHO Grade I, and genetic analysis revealed the H3 K27M mutation. However, although the radiological, surgical, and pathological findings all corresponded to PA, this entity can easily be misdiagnosed as diffuse midline glioma with the H3 K27M mutation, which is classified as a WHO Grade IV tumor according to the updated classification. This case highlights the phenotypic spectrum of PA, as well as the biology of the H3 K27M–mutated gliomas, and may prove to be an exception to the rule that diffuse midline gliomas with the H3 K27M mutation behave in an aggressive manner. Based on the findings of this case, the authors conclude that, in addition to detecting the existence of the H3 K27M mutation, an integrated approach in which a combination of clinical, pathological, and genetic information is used should be applied for accurate diagnosis and determination of the appropriate treatment for diffuse midline gliomas.

OBJECTIVEWHO 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.METHODSClinical 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).RESULTSThe 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.CONCLUSIONST2-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.

Objective This study aimed to evaluate the efficacy of stereotactic radiotherapy combined with bevacizumab (SRT-Bv) compared with Bv treatment for recurrent high-grade gliomas (HGGs). Methods Data for patients with recurrent HGGs who received SRT and Bv (n = 29) or Bv (n = 29) between June 2014 and September 2016 were retrospectively analyzed. All patients received conventional radiotherapy (total, 60 Gy) before this study. SRT was administered at a median dose of 42 Gy in 3–7 fractions. The recurrence pattern was classified into 3 groups: in-field, marginal, and out-field. Results The median overall survival in the SRT-Bv group was significantly longer than that in the Bv group (10.4 vs. 5.6 months; P = 0.02). In patients with isocitrate dehydrogenase wild-type tumors, the SRT-Bv treatment significantly prolonged survival more than the Bv treatment (10.9 vs. 8.2 months; P = 0.01). The World Health Organization grade and presence or absence of SRT were significant prognostic factors in the univariate analysis. Besides brain edema in 2 cases and asymptomatic subdural hematoma in 1 case, no other severe adverse effect due to SRT-Bv treatment was recorded. The pattern of recurrence was as follows: in-field, 2 cases (7%); marginal, 8 cases (28%); out-field, 11 cases (38%); no recurrence on radiologic findings, 6 cases (21%); and uncertain, 2 cases (7%). Conclusions SRT-Bv treatment significantly prolonged survival duration more than Bv treatment and provides good local control in patients with recurrent HGGs, especially those with isocitrate dehydrogenase wild-type tumors.

Objective Accurate preoperative and intraoperative differentiation between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is sometimes difficult. Distinguishing between these tumors during surgery is important because surgical treatment is different between the 2 tumors. In this study, we established a new method of intraoperative differentiation between PCNSL and GBM using intraoperative flow cytometry (iFC), and we retrospectively tested whether iFC was useful for the intraoperative diagnosis of PCNSL and GBM. Methods We analyzed the iFC data of 250 patients (28 with PCNSL and 222 with GBM) and then evaluated aneuploidy and S-phase population. Results Aneuploidy was detected in 54.5% of GBM cases but in only 7.14% of PCNSL cases. Aneuploidy indicated GBM, but it was difficult to distinguish PCNSL from GBM when a tumor had a diploid pattern. Thus, for tumors without aneuploidy, we evaluated the S-phase population: S2, the ratio of the average height of the S-phase to the height of the diploid peak. S2 was significantly higher in PCNSL than in GBM. Based on these results, we established an algorithm for differentiating between PCNSL and GBM using DNA aneuploidy and S2. Comparing this new iFC algorithm and the permanent pathologic diagnosis, the sensitivity was 89.3%, the specificity was 93.7%, and the accuracy was 93.2%. Conclusions iFC is useful for the intraoperative differentiation between PCNSL and GBM and it aids in intraoperative decision making within a short time. The accuracy of intraoperative diagnosis of these tumors seems to be higher with the combination of iFC and intraoperative rapid pathologic diagnosis.