scholarly journals NI-6 Preoperative differential diagnosis of grade II and grade III in cases with astrocytoma, IDH mutant

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi18-vi19
Author(s):  
Hirohito Yano ◽  
Kazuhiro Miwa ◽  
Noriyuki Nakayama ◽  
Takashi Maruyama ◽  
Naoyuki Ohe ◽  
...  

Abstract Purpose: We attempted to differentiate between IDH-mutant astrocytoma Grade II and grade III by using methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Subjects and Methods: We retrospectively analyzed 41 adult supratentorial glioma cases with confirmed histological diagnosis and IDH status from June 2015 to June 2020. These included 21 males, with an average age of 38.5 years (19–59 years), including seven astrocytoma grade II (A-II) and 34 grade III (A-III) cases. We determined the accumulation value rate of the maximum tumor to normal cortex accumulation value (T/N ratio) in MET-PET. We obtained the peak ratios of N-acetyl aspartate (NAA)/ creatine (Cr), choline (Cho)/Cr, and Cho/NAA. We investigated the correlation between the T/N ratios and MRS parameters and examined the contrast effects on MRI. Results: There were no significant differences in the T/N ratio and MRS parameters between A-IIs and A-IIIs. Only Cho/NAA ratios were significantly correlated with the T/N ratios (r = 0.443, P = 0.0037). We divided the distribution map into four areas with the highest T/N ratio of AII (1.59) and the highest Cho/NAA ratio (3.66). That is, 1) T/N ratio ≤ 1.59 & Cho/NAA ≤ 3.66, 2) >1.59 & ≤ 3.66, 3) ≤1.59 & > 3.66, 4) &gt 1.59 & &gt 3.66. The diagnostic rates for A-III were 1) 61.1% (11/18), 2) 100% (7/7), 3) 100% (9/9), and 4) 100% (7/7). We found the contrast effects in only 7 cases (20.6%) of A-III, which were distributed in areas 2) to 4). Conclusion: A-IIs and A-IIIs distributed in area 1) were difficult to distinguish, and they need careful observation as a step before the transition to areas 2)-4). Meanwhile, A-IIIs reaching widespread distribution to areas 2)-4) because of their wide range of malignancies require clinically aggressive treatment. The method might be beneficial in grade analysis of IDH-mutant astrocytomas.

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii159-ii160
Author(s):  
Roberta Rudà ◽  
Riccardo Pascuzzo ◽  
Francesca Mo ◽  
Alessia Pellerino ◽  
Peter B Barker ◽  
...  

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii149-ii149
Author(s):  
Lazaros Lazaridis ◽  
Sied Kebir ◽  
Manuel Weber ◽  
Teresa Schmidt ◽  
Kathy Keyvani ◽  
...  

Abstract BACKGROUND Advanced imaging techniques entered the field of neurooncology. In this analysis we compare the diagnostic potential of 18F-fluorethyltyrosine (FET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) in their potential to preoperatively predict certain glioma subtypes. AIMS Goal of this analysis ist the evaluation of FET PET and MRS regarding the preoperative prediction of glioma subtypes. METHODS We analyzed 33 patients with histopathologically confirmed newly diagnosed glioma. The patients received FET PET and MRS during one single preoperative diagnostic session. According to the molecular portfolio patients were subdivided in IDH wildtype glioblastoma patients (GBM), IDH wildtype WHO grade II/III glioma patients (Astro_IDHwt), IDH mutant WHO grade II/III glioma patients without 1p/19q codeletion (Astro_IDHmut) and with 1p/19q codeletion (ODG). Mean and maximum tumor-to-brain ratio (TBRmean and TBRmax), N-acetylaspartate, choline and creatine peaks were correlated with postoperative tumor diagnosis. To gain generalizable implications we subdivided the study cohort into a development and validation subcohort. A support vector machine model was fitted to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic curve served to assess model performance. RESULTS GBM patients had highest TBRmax and TBRmean values (mean: 3.5 and 3.8) and the ODG patients showed the second highest TBRmax and TBRmean values (mean: 2.6 and 3). The distribution of MRS markers exhibited to clear trend. The performance of glioma subtyping was comparatively low for the TBR values (AUC: 0.68) and even lower for the MRS markers (AUC: 0.60). These results are in line with preliminary investigations performed by our institute for the comparison of 11C-methionine PET with MRS in preoperative glioma subtyping. CONCLUSIONS FET PET and MRS bear limited potential in glioma subgrouping. However, FET PET appears to be slightly superior. Investigation in a larger cohort is required to draw definite conclusions.


2021 ◽  
Vol 11 ◽  
Author(s):  
Rashmi Rana ◽  
Kirti Chauhan ◽  
Poonam Gautam ◽  
Mahesh Kulkarni ◽  
Reema Banarjee ◽  
...  

Gliomas are the most common type of the malignant brain tumor, which arise from glial cells. They make up about 40% of all primary brain tumors and around 70% of all primary malignant brain tumors. They can occur anywhere in the central nervous system (CNS) and have a poor prognosis. The average survival of glioma patients is approximately 6–15 months with poor aspects of life. In this edge, identification of proteins secreted by cancer cells is of special interest because it may provide a better understanding of tumor progression and provide early diagnosis of the diseases. Extracellular vesicles (EVs) were isolated from pooled plasma of healthy controls (n=03) and patients with different grades of glioma (Grade I or II or III, n=03 each). Nanoparticle tracking analysis, western blot, and flow cytometry were performed to determine the size, morphology, the concentration of glioma-derived vesicles and EV marker, CD63. Further, iTRAQ-based LC-MS/MS analysis of EV protein was performed to determine the differential protein abundance in extracellular vesicles across different glioma grades. We further verified galectin-3 binding protein (LGALS3BP) by ELISA in individual blood plasma and plasma-derived vesicles from control and glioma patients (n=40 each). Analysis by Max Quant identified 123 proteins from the pooled patient exosomes, out of which 34, 21, and 14 proteins were found to be differentially abundant by more than 1.3-fold in the different grades of glioma grade I, pilocytic astrocytoma; grade II, diffuse astrocytoma; grade III, anaplastic astrocytoma, respectively, in comparison with the control samples. A total of seven proteins—namely, CRP, SAA2, SERPINA3, SAA1, C4A, LV211, and KV112—showed differential abundance in all the three grades. LGALS3BP was seen to be upregulated across the different grades, and ELISA analysis from individual blood plasma and plasma-derived extracellular vesicles confirmed the increased expression of LGALS3BP in glioma patients (p<0.001). The present study provides LGALS3BP as a potential biomarker for early detection of glioma and improve survival outcome of the patient. The present study further provides the information of progression and monitoring the tumor grades (grade 1, grade II, grade III).


2019 ◽  
Vol 7 (21) ◽  
pp. 3514-3520
Author(s):  
Mohanad Mundher Abdulghani ◽  
Mohamad Natiq Abbas ◽  
Wafaa Redha Mohammed

BACKGROUND: Diffuse astrocytomas constitute the largest group of primary malignant human intracranial tumours. They are classified by the World Health Organization (WHO) into three histological malignancy grades: diffuse astrocytomas (grade II), anaplastic astrocytomas (grade III) and glioblastoma (grade IV) based on histopathological features such as cellular atypia, mitotic activity, necrosis and microvascular proliferation. Epidermal growth factor receptor (EGFR) is a 170-kDa transmembrane tyrosine kinase receptor expressed in a variety of normal and malignant cells regulating critical cellular processes. When activated, epidermal growth factor receptor (EGFR) triggers several signalling cascades leading to increased proliferation and angiogenesis and decreased apoptosis and hence associated with aggressive progression of the tumour. Epidermal growth factor receptor (EGFR) level is known to be a strong indicator associated with the aggressive behaviour of the tumour and acts as a prognostic factor for evaluating the survival rate. AIM: To evaluate the expression of epidermal growth factor receptor (EGFR) in different grades of astrocytoma. MATERIAL AND METHODS: formalin-fixed paraffin-embedded astrocytic tumours of 44 patients were collected from the archival material of pathology department of Ghazi Al Hariri Teaching Hospital during the period from June to December 2018. Hematoxylin and eosin-stained sections were used to characterise the tumours histologically based on cellularity, nuclear hyperchromasia, polymorphism, mitotic activity, vascular proliferation and necrosis with or without pseudopallisading of tumour cells. Diagnosis and grading of astrocytic tumours in this study were made according to WHO criteria (2016). Using a monoclonal antibody to the epidermal growth factor receptor (EGFR) and immunohistochemical analysis, the expression and distribution of epidermal growth factor receptor in astrocytic tumours were examined. RESULTS: The study included 1 case pilocytic astrocytoma (grade I), 20 cases diffuse astrocytoma (grade II), 5 cases anaplastic astrocytoma (grade III) and 18 cases of glioblastoma (grade IV). Expression of EGFR was found in 38.88% of the glioblastoma samples (grade IV). However, none of the astrocytomas of WHO grades I, II and III showed immunoreactivity for EGFR protein. Different patterns of immunoreactive cells and significant intratumor heterogeneity of EGFR expression were observed in glioblastomas. CONCLUSION: The immunohistochemical expression of Epidermal growth factor receptor (EGFR) was restricted only to high-grade astrocytic tumours, namely glioblastoma, thus may use to predict glioblastoma.


Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 842-846 ◽  
Author(s):  
Yuji Suzuki ◽  
Yukihiro Nakamura ◽  
Kenichi Yamada ◽  
Satoshi Kurabe ◽  
Kouichirou Okamoto ◽  
...  

Abstract BACKGROUND Aquaporin (AQP) water channels play a significant role in mesenchymal microvascular proliferation and infiltrative growth. AQPs are highly expressed in malignant astrocytomas, and a positive correlation is observed between their expression levels and histological tumor grade. OBJECTIVE To examine the utility of aquaporin positron emission tomography (PET) for differentiating between astrocytoma grade III and grade IV using the AQP radioligand [11C]TGN-020. METHODS Fifteen astrocytoma patients, grade III (n = 7) and grade IV (n = 8), and 10 healthy volunteers underwent [11C]TGN-020 aquaporin PET imaging. Surgical tissues of astrocytoma patients were examined for histopathological grading using the WHO classification standard and expression of AQP1 and AQP4 immunohistochemically. RESULTS Mean standardized uptake values of astrocytoma grade III and IV (0.51 ± 0.11 vs 1.50 ± 0.44, respectively) were higher than normal white matter (0.17 ± 0.02, P < .001) for both tumor grades. Importantly, mean standardized uptake values of astrocytoma grade IV were significantly higher than grade III (P < .01). CONCLUSION Our study demonstrated that [11C]TGN-020 aquaporin PET imaging differentiated between astrocytoma grades III and IV. We suggest its clinical application as a noninvasive diagnostic tool would lead to advancements in the management of these malignant brain tumors.


Author(s):  
А.В. Бойко ◽  
Н.Д. Олтаржевская ◽  
В.И. Швец ◽  
Л.В. Демидова ◽  
Е.А. Дунаева ◽  
...  

Цель исследования. Разработка методов сопроводительной терапии для защиты нормальных органов и тканей, входящих в зону облучения. Методы. В исследование включено 112 больных раком шейки и тела матки после комбинированного или самостоятельного лучевого лечения с 2012 по 2016 гг. У 71 пациентки основной группы в качестве терапии сопровождения применяли гидрогель с деринатом и у 41 больной группы контроля - традиционные методы профилактики (масло оливковое, подсолнечное, метилурациловая мазь). Для профилактики эпителиита слизистой влагалища и шейки матки в основной группе использовали гидрогель в виде аппликаций с первого дня облучения. Для профилактики лучевого ректита гидрогель вводили в прямую кишку 1 раз в день с первого дня облучения. Инстилляции гидрогеля в мочевой пузырь начинали только при развитии первых признаков клинической картины цистита. Пациенткам контрольной группы для профилактики лучевых реакций проводились масляные, мазевые аппликации во влагалище, масляные микроклизмы в прямую кишку с первого дня облучения. Лечение лучевого цистита проводили с помощью растительных диуретиков, уросептиков. Результаты. Применение гидрогеля с деринатом позволило провести курс лучевой терапии без перерыва у 84,5% (60/71) больных, в контрольной группе - лишь у 48,8% (20/41). Лучевые циститы возникали в 2,5 раза реже (25,3% ± 3,3 против 63,4% ± 2,7, р<0,01). Анализ степени выраженности лучевого цистита по RTOG в двух группах показал, что у 75% больных основной группы наблюдалась I степень, у 25% - II степень, III и IV степени не отмечено, тогда как в контрольной группе лучевой цистит I степени развился у 44% пациенток, II - 40% и III - 16% больных. Применение гидрогеля снизило частоту лучевых ректитов в 2 раза (26,7% ± 3,3 против 53,7% ± 3,2 р<0,1).При использовании ежедневных аппликаций гидрогеля с деринатом со стороны слизистой оболочки влагалища и шейки матки преобладали эпителииты I степени (53,5%), II степень наблюдалась у 29,5% и III степень лучевой реакции - лишь в 16,9% случаев, IV степень реакции не отмечена. В контрольной группе эти показатели составили 26,8%, 24,3%, 31,7% и 17,2% соответственно. Разработаны цитологические критерии оценки течения лучевых реакций слизистой влагалища. Выделены три степени изменения цитограммы, которые коррелировали с клинической картиной. В основной группе лучевые изменения I степени зафиксированы в 4,5 раза чаще (52 ± 9,9% против 11,5 ± 6,3%, р<0,002), а III степень представлена в 3,8 раза реже, чем в контрольной группе (12 ± 6,5% против 46,1 ± 9,8%, р<0,003). Заключение. Применение гидрогелевого материала с деринатом в качестве препарата сопроводительной терапии во время курса облучения позволяет уменьшить частоту и степень выраженности лучевых повреждений со стороны слизистой влагалища, мочевого пузыря и прямой кишки, провести курс лучевой терапии без перерыва и улучшить качество жизни пациенток. Objective. Development of methods for accompanying therapy to protect normal organs and tissues in the irradiation zone. Method. The study included 112 patients with cervical and endometrial cancer after combined or independent radiotherapy from 2012 to 2016. In 71 female patients of the main group, Derinat with hydrogel was applied as a supportive therapy and in 41 patients of the control group, conventional prevention methods (olive oil, sunflower oil, methyluracyl ointment) were applied. For prevention of vaginal mucosal and cervical epitheliitis in the main group, hydrogel was used as applications from the first radiation day. For prevention of radiation proctitis, hydrogel was injected into the rectum once daily from the first radiation day. Hydrogel instillations into the bladder were started only with the first clinical signs of cystitis. For prevention of radiation reactions, vaginal oil and ointment and rectal oil micro-enema were administered to patients of the control group from the first day of irradiation. Radiation cystitis was treated with vegetable diuretics and uroseptic drugs. Results. Using the hydrogel with Derinat allowed to administer a course of radiotherapy without interruption in 84.5% (60/71) of patients and only in 48.8% (20/41) in the control group. Radiation cystitis occurred 60% less frequently (25.3% ± 3.3 versus 63.4% ± 2.7, p <0.01). Analysis of radiation cystitis severity in two groups (according to RTOG) showed that 75% of patients in the main group had grade I and 25% had grade II. Grade III and grade IV did not occur. At the same time, in the control group, grade I radiation cystitis developed in 44% of patients, grade II - in 40%, and grade III - in 16% of patients. The hydrogel treatment halved the frequency of radiation proctitis (26.7% ± 3.3 vs. 53.7% ± 3.2 p <0.1). With daily application of the hydrogel with Derinat, grade I epitheliitis (53.5%) predominated in vaginal and cervical mucosa, grade II was observed in 29.5%, and grade III radiation reaction - only in 16.9% of cases; grade IV reaction was not observed. In the control group, these proportions were 26.8%, 24.3%, 31.7%, and 17.2%, respectively. Cytological criteria were developed to evaluate the course of radiation reactions in the vaginal mucosa. Three degrees of change in the cytogram were identified, which correlated with clinical picture. In the main group, incidence of grade I radiation-induced changes was increased by more than 350% (52 ± 9.9% vs. 11.5 ± 6.3%, p <0.002), and incidence of grade III was decreased by more than 70% compared to the control group (12 ± 6.5% vs. 46.1 ± 9.8%, p <0.003). Conclusion. Using the hydrogel material with Derinat as an accompanying therapy during the course of irradiation allows to reduce frequency and severity of radiation injuries of the vaginal mucosa, bladder, and rectum, administer an uninterrupted course of radiotherapy, and improve the quality of life of patients.


2007 ◽  
Vol 107 (3) ◽  
pp. 600-609 ◽  
Author(s):  
Robert G. Whitmore ◽  
Jaroslaw Krejza ◽  
Gurpreet S. Kapoor ◽  
Jason Huse ◽  
John H. Woo ◽  
...  

Object Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms. Methods Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade. Results In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96–3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27–2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59–6.26; four patients) and Group 2 (mean 2.83, range 1.81–3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59–6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96–3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively. Conclusions Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 985
Author(s):  
Luisa Müller ◽  
Nicole Power Guerra ◽  
Jan Stenzel ◽  
Claire Rühlmann ◽  
Tobias Lindner ◽  
...  

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.


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