Role of cyclin D1 in glial tumors—A retrospective and observational study

Aim: High-grade glial tumors remain as one of the most lethal malignancies. Cyclin D1 is expressed in some human malignancies and is the potential target of intervention. The present study aims to determine the relationship of cyclin D1 expression with other clinicopathological parameters. Materials and Methods: A cross-sectional study was carried out in a tertiary care center. Biopsy proven 66 cases of glial tumor patients were included in the study. The patients with incomplete clinical details were excluded from the study. Immunohistochemistry using antibodies for IDH 1 and cyclin d1 was done in all the cases. Glial tumors were reclassified according to WHO 2016 classification. Data analysis was performed using SPSS 26.0 for the windows. Result: Among 66 patients, 49 (74.3%) were males and 17 (25.7%) were females. The age of the patients ranged from 20 years to 70 years. Overall, 6.02% were of grade I Glial tumors, 22.7% were of grade II Glial tumors, 19.6% patients were of grade III Glial tumors, and 51.6% patients were of grade IV Glial tumors. Of 66 samples tested cyclin D1 was positive in 25 (37.87%) as high expressers and 7 (10.60%) were low expressers. Our study showed a significant correlation between the expression of cyclin D1 with grade and IDH mutation status, No significant correlation of cyclin D1 was noted with age or sex of the patient. Conclusion: Cyclin D1 was associated with a higher grade of the glial tumor. It can be a potential marker both for prognosis and treatment of glial tumors.

Anaplastic Astrocytoma Mimicking Herpes Simplex Encephalitis

No abstract available.

Value of Perfusion Weighted Magnetic Resonance Imaging in the Diagnosis of Supratentorial Anaplastic Astrocytoma

We report perfusion weighted imaging (PWI) findings of nonenhanced anaplastic astrocytoma in a 30-year-old woman. Brain magnetic resonance imaging showed a nonenhanced brain tumor with mild peritumoral edema on the right medial frontal lobe and right genu of corpus callosum, suggesting a low-grade glioma. However, PWI showed increased relative cerebral blood volume, relative cerebral blood flow, and permeability of nonenhanced brain tumor compared with contralateral normal brain parenchyma, suggesting a high-grade glioma. After surgery, final histopathological analysis revealed World Health Organization grade III anaplastic astrocytoma. This case demonstrates the importance of PWI for preoperative evaluation of nonenhanced brain tumors.

Value of Perfusion Weighted Magnetic Resonance Imaging in the Diagnosis of Supratentorial Anaplastic Astrocytoma

We report perfusion weighted imaging (PWI) findings of nonenhanced anaplastic astrocytoma in a 30-year-old woman. Brain magnetic resonance imaging showed a nonenhanced brain tumor with mild peritumoral edema on the right medial frontal lobe and right genu of corpus callosum, suggesting a low-grade glioma. However, PWI showed increased relative cerebral blood volume, relative cerebral blood flow, and permeability of nonenhanced brain tumor compared with contralateral normal brain parenchyma, suggesting a high-grade glioma. After surgery, final histopathological analysis revealed World Health Organization grade III anaplastic astrocytoma. This case demonstrates the importance of PWI for preoperative evaluation of nonenhanced brain tumors.

Glioma Mimicking a Hypertensive Intracerebral Hemorrhage

Here, we report a rare case of an anaplastic astrocytoma masquerading as a hypertensive basal ganglia hemorrhage. A 69-year-old woman who had been under medical management for hypertension during the past 3 years suddenly developed right hemiparesis with dysarthria. Brain computed tomography (CT) scans with contrast and CT angiograms revealed an intracerebral hemorrhage (ICH) in the left basal ganglia, without an underlying lesion. She was treated conservatively, but underwent a ventriculoperitoneal shunt operation 3 months after the initial attack due to deteriorated mental status and chronic hydrocephalus. Three months later, her mental status deteriorated further. Magnetic resonance imaging (MRI) with gadolinium demonstrated an irregular enhanced mass in which the previous hemorrhage occurred. The final histological diagnosis which made by stereotactic biopsy was an anaplastic astrocytoma. In the present case, the diagnosis of a high grade glioma was delayed due to tumor bleeding mimicking hypertensive ICH. Thus, a careful review of neuroradiological images including MRI with a suspicion of tumor bleeding is needed even in the patients with past medical history of hypertension.

An Infant with Prenatally Diagnosed Congenital Anaplastic Astrocytoma Who Remains Disease-Free after Proton Therapy

The authors present a rare of prenatally diagnosed congenital anaplastic astrocytoma. A 9-month-old boy had three recurrences despite two surgical resections and various chemotherapeutic regimens. He underwent the 3rd gross tumor removal at 11 months of age, followed by proton therapy, and now he remains disease-free for 3 yr without a significant neurocognitive dysfunction. This is the 1st case of a pediatric tumor treated by proton therapy in Korea, and proton therapy may be a treatment of choice for a congenital anaplastic astrocytoma in infants and young children, considering limitation of radiation therapy.

The Role of Chemotherapy in Anaplastic Astrocytoma Patients

OBJECTIVE: This retrospective study was performed to evaluate the role of chemotherapy in the management of patients with anaplastic astrocytoma (AA). METHODS: We compared the survival outcome among the 3 different treatment protocol groups in a single institution. A total of 86 patients (39 men and 47 women) with newly diagnosed AA after surgery were analyzed. Among them, 31 patients (36.0%) were treated with radiotherapy only (RT Group), 30 patients (34.9%) were treated with nimustine-cisplatin chemotherapy before RT (ACNU-CDDP group), and 25 patients (29.1%) were treated with procarbazine, lomustine and vincristine (PCV) chemotherapy after radiotherapy (PCV group). RESULTS: The median survival was 14.0, 30.0 and 72.0 months in RT, ACNU-CDDP, and PCV group, respectively and showed significant differences (RT vs. ACNU-CDDP; p=0.039, RT vs. PCV; 0.002, ACNU-CDDP vs. PCV; 0.045). PCV group showed less toxicity rate (5 patients; 20%) than ACNU-CDDP group (12 patients; 40%), while only 3 patients (9.6%) in RT group experienced grade 3 or 4 toxicities. CONCLUSION: An application of chemotherapy before or after radiotherapy is beneficial in prolonging the survival of patients with AA. Adjuvant PCV chemotherapy after radiotherapy is recommendable.

The Role of Chemotherapy in Anaplastic Astrocytoma Patients

OBJECTIVE: This retrospective study was performed to evaluate the role of chemotherapy in the management of patients with anaplastic astrocytoma (AA). METHODS: We compared the survival outcome among the 3 different treatment protocol groups in a single institution. A total of 86 patients (39 men and 47 women) with newly diagnosed AA after surgery were analyzed. Among them, 31 patients (36.0%) were treated with radiotherapy only (RT Group), 30 patients (34.9%) were treated with nimustine-cisplatin chemotherapy before RT (ACNU-CDDP group), and 25 patients (29.1%) were treated with procarbazine, lomustine and vincristine (PCV) chemotherapy after radiotherapy (PCV group). RESULTS: The median survival was 14.0, 30.0 and 72.0 months in RT, ACNU-CDDP, and PCV group, respectively and showed significant differences (RT vs. ACNU-CDDP; p=0.039, RT vs. PCV; 0.002, ACNU-CDDP vs. PCV; 0.045). PCV group showed less toxicity rate (5 patients; 20%) than ACNU-CDDP group (12 patients; 40%), while only 3 patients (9.6%) in RT group experienced grade 3 or 4 toxicities. CONCLUSION: An application of chemotherapy before or after radiotherapy is beneficial in prolonging the survival of patients with AA. Adjuvant PCV chemotherapy after radiotherapy is recommendable.

Intracranial Dissemination from Spinal Cord Anaplastic Astrocytoma

We report a case of intracranial dissemination developing approximately 4 months after partial removal of a spinal cord anplastic astrocytoma in a 22-year-old male. He presented with paraplegia on initial admission at a local hospital. Spinal magnetic resonance (MR) images disclosed multiple intramedullary lesions at the T3-11. The tumor was partially removed. The final histologic diagnosis was anaplastic astrocytoma. Four months after the operation, he was admitted with the symptoms of headache and deterioration of consciousness. MR images showed enhanced lesions in the anterior horn of the left lateral ventricle, and septum pellucidum. He underwent computed tomography-guided stereotactic biopsy and histological appearance was consistent with anaplastic astrocytoma. The clinical course indicates that the tumor originated in the spinal cord and extended into the subarachnoid space, first the spinal canal and later intracranial.

Impacto da adição da temozolamida à radioterapia no tratamento de crianças portadoras de tumor de tronco cerebral / Impact of the addition of temozolomide to radiotherapy in the treatment of children with brain stem tumors

OBJETIVO: Analisar o impacto da adição da temozolamida à radioterapia em tumores de tronco cerebral em crianças. MATERIAL E MÉTODO: Entre 2000 e 2005 foram analisadas, retrospectivamente, 64 crianças com tumor do tronco cerebral. Dessas crianças, 32 receberam temozolamida(grupo 1) e 32 não a receberam (grupo 2). RESULTADOS: A idade mediana no grupo 1 foi de 8,2 anos e no grupo 2 foi de 7,5 anos. A localização tumoral era predominantemente difusa (53%) emambos os grupos. Todos os pacientes receberam radioterapia com doses superiores a 50 Gy. No grupo1 foram ministrados nove ciclos, em média, de quimioterapia (3û14 ciclos). O tempo de progressão de doença foi de 7,9 meses no grupo 2 versus 13,8 meses no grupo 1. A sobrevida global foi de 8,8 meses (0,3û30,9 meses) no grupo 1 e de 14,6 meses (4,3û33 meses) no grupo 2. CONCLUSÃO: A utilização da temozolamida após a radioterapia proporcionou aumento da sobrevida, deseis meses em média, nos pacientes pediátricos com tumor do tronco cerebral.

OBJECTIVE: To analyze the impact of adding temozolomide to radiotherapyin pediatric brain stem tumors. MATERIAL AND METHOD: Between 2000 and 2005, 64 children with brain stem tumor were analyzed: 32 received temozolomide (group 1) and 32 did not(group 2). RESULTS: The median age of patients in group 1 was 8.2 year-old and in group 2 was 7.5 year-old. The predominant tumoral localization was diffuse (53%) in both groups. All of the patients were submitted to radiotherapy. In group 1, the median number of temozolomide cycles was 9 (3û14 cycles). Time of disease progression was 7.9 months in group 2 versus 13.8 months in group 1. Overall survival was 8.8 months (0.3û30.9 months) in group 1 and 14.6 months (4.3û33 months) in group 2. CONCLUSION: In our institution,adding temozolomide to radiotherapy increased the overall survival in approximately six months in brain stem pediatric tumors.

Clinical Study: Phase II Study of Continuous ACNU (nimustine) and CDDP (cisplatin) Infusion Followed by Conventional Radiotherapy in Patients with High Grade Astrocytomas

OBJECTIVE: This study is aimed at evaluating the efficacy and the toxicity of a 72-hour continuous intravenous infusion of ACNU and CDDP before radiotherapy in adult patients with newly diagnosed anaplastic astrocytoma and glioblastoma. METHODS: Forty-three adult patients with a postoperative Karnofsky performance status greater than 60 were entered into this protocol without any prior treatment. Two cycles of preradiation chemotherapy were performed at 6-week intervals. Conventional radiotherapy was begun 6 weeks later. Magnetic resonance (MR) imaging studies were conducted pre- and postoperatively, and follow-up MR images at the beginning of each treatment and every three months after radiotherapy completion. Response rate, survival rate, prognostic factors and complications were evaluated. RESULTS: Among 43 patients mentioned above, twenty-one patients completed two cycles of chemotherapy. One patient showed complete remission, ten partial response, seven stable disease and three progressive disease. The median survival time was 15.9 months. Overall response rate was 22.3%. Twenty-seven showed pancytopenia, including two bleeding tendencies, one intracerebral hemorrhage resulting to death, and another two infections. Considering the prognostic factors, only a mutated p53 level of under 20%(% of tumor cells containing mutated p53) was correlated with survival prolongation. Prognostic factor of age under 45 was the only significant factor of extending the time to progression. CONCLUSION: This treatment protocol shows favorable results of preradiation chemotherapy using ACNU and CDDP.

Intracranial Anaplastic Astrocytoma after Radiotherapy for Craniopharyngioma

The authors describe a case of 17-year-old male with anaplastic astrocytoma in the basal ganglia and brain stem 11 years after surgical excision and local irradiation(5480cGy) for craniopharyngioma. There is no recurrence at the primary tumor site. Because of a geometric coincidence between the tumor location and the radiation field, radiation therapy is strongly implicated as a cause of this anaplastic astrocytoma.

A Case of Anaplastic Astrocytoma Presented with Symptoms of the Brain and Spinal Cord as a First Manifestation

A 34-year-old woman complained of left facial palsy and numbness on the left thigh that began two weeks prior with headaches. Brain MRI revealed ill-defined patchy T2 weighted high signal intensities in the right medial temporal lobe and thalamus without contrast enhancement. Ten days later, when she complained of sensory symptoms below the 7th thoracic cord, we found an enhancing lesion in the lower cervical cord on the MRI. The result from the brain biopsy was consistent with anaplastic astrocytoma.

A Case of Anaplastic Astrocytoma Presented with Symptoms of the Brain and Spinal Cord as a First Manifestation

A 34-year-old woman complained of left facial palsy and numbness on the left thigh that began two weeks prior with headaches. Brain MRI revealed ill-defined patchy T2 weighted high signal intensities in the right medial temporal lobe and thalamus without contrast enhancement. Ten days later, when she complained of sensory symptoms below the 7th thoracic cord, we found an enhancing lesion in the lower cervical cord on the MRI. The result from the brain biopsy was consistent with anaplastic astrocytoma.

The Long-Term Survival in Patients with Anaplastic Astrocytoma or Glioblastoma

OBJECTIVE: The authors present an analysis of the long-term survivors with malignant glioma to find out their characteristics and the prognostic factors responsible for the long-term survival. METHODS: Forty two patients with histologically confirmed astrocytoma grade III or IV in adults(age> or =15) were included in this study. Medical records, radiological and histological findings were reviewed retrospectively. We compared the long-term survival group(LTSG, survival> or =5 years) with the group of patients who survived less than five years for the clinical, pathological, radiological factors and treatment modality. Additionally, survival analysis was performed to identify the prognostic factors for the whole patients with malignant glioma. RESULTS: Six of the 42 patients showed long-term survival(5-13 years) after diagnosis of anaplastic astrocytoma or glioblastoma. The mean age of LTSG was 41.8 years. We found histological dedifferentiation from low-to high-grade glioma in 4 cases. All of 6 patients were received aggressive multi-modality therapy including postoperative radiation and chemotherapy. Age(under 60 years), dedifferentiation and number of operation were significantly related to the LTSG. In multivariate analysis for the whole patients, we found that the age and postoperative radiotherapy were significant prognostic factors for malignant gliomas. CONCLUSION: The young age, prior history of low-grade glioma and repeated debulking surgeries are significantly associated with the long-term survival. Aggressive multidisciplinary approach is highly recommended in young patients with malignant glioma to increase the chance of long-term survival.

A Case of Anaplastic Astrocytoma in Term Pregnancy / 대한주산의학회잡지

Intracranial astrocytoma is often discovered in third-fifth decade and occupies about 12% of the intracranial tumor patients. The concurrence of tumors of the brain and pregnancy is uncommon, moreover, astrocytoma of the brain in term pregnancy is very rare. Generally, astrocytoma is divided into six subgroups. Among them anaplastic astrocytoma is thought to be a malignant brain tumor. In the management of patients with brain tumor complicating pregnancy, judgments with regard to the optimal time for neurologic studies and operation and the mode of delivery are frequently difficult and occasionally controversial. We experienced a case of anaplastic astrocytoma of left frontal lobe, which was diagnosed by MR imaging at the third trimester of pregnancy. We report the case with a brief review of literature.

Collision Tumor of Meningioma and Anaplastic Astrocytoma

Multiple primary brain tumors of different cell types are rare, accounting for 0.4% of all the primary brain tumors. Phakomatosis, irradiation, trauma and other factors have been associated with multiplicity of brain tumors. When these tumors are close or intermixed, the term "collision" has been used, and in these cases an explanation might be that one tumor stimulating the other. We report a patient with collision tumor of meningioma and anaplastic astrocytoma, who did not have a history of trauma, irradiation, or phakomatosis.

p53 Gene Mutations in Astrtocytoma Detection by Direct DNA Sequencing / 대한암학회지

PURPOSE: Mutations in the p53 gene have been recognized in brain tumor, and clonal expansion of p53 mutant cells has been shown to be associated with glioma progression. However, studies on the p53 gene have been limited by the need for fresh frozen tissues. We have tried a method utilizing polymerase chain reaction (PCR) for the direct DNA sequecing of the p53 gene using a single 10 m paraffin-embedded tissue section. We applied this method to detect for p53 gene mutations in exons 5~8 in human astrocytoma utilizing paraffin-embedded tissues. MATERIALS AND METHODS: Twenty paraffin blocks containing tumor were selected from surgical specimens from twenty different cases. Tumors included 10 astrocytomas and 10 anaplastic astrocytomas. Ten controls were also selected among autopsy cases showing normal brain in light microscopy. The tissue section on the stained glass slide was used to guide microdissection of an unstained adjacent tissue section to ensure above 90% of the tumor cell population for p53 mutational analysis. RESULT: Mutation in the p53 gene was identified in 1 of 10 (10%) anaplastic astrocytomas. Mutations in the p53 gene were identified in 1 of 10 cases (10%) by PCR and direct DNA sequencing. Mutation in exon 7 resulting in amino acid substitution was found in one anaplastic astrocytoma (codon 245, GGC-->GAC: glycine-->aspartic acid). Ten control cases, ten astrocytomas and nine anaplastic astrocytomas were confirmed to be negative by direct sequencing of amplified DNA. CONCLUSION: This study demonstrates the feasibility of evaluating p53 gene mutations in archived astrocytoma specimens using PCR and direct DNA sequencing on paraffin sections. Application of this method should facilitate investigation of the role of p53 gene mutations in tumor biology.

An Analysis of Combined interferon-beta, BCNU and Radiation in the Treatment of Malignant Glioma

Prognosis for patients with a malignant glioma of the brain is, up to the present time, very poor. Surgery is unlikely to be curative and the primary goals of the surgery are:(1) to make a histologic diagnosis, (2) to determine the extent of the lesion and (3) if possible, to debulk the tumor. The inclusion of radiation therapy following surgery prolonged median survival time by about 0 weeks as compared to surgery alone or surgery with chemotherapy. 50 patients with anaplastic astrocytoma or glioblastoma multiforme were treated at the Department of Neurosurgery. C.U.M.C. Mar. 1991 and Jul. 1994. All patients were treated with surgical resection, irradiation, chemotherapy with BCNU(1, 3bis(2chloroentlyl) 1nitrosourea), and immunotherapy with interferon beta(IBR therapy). Interferon beta was given in dosages of 100,000~300,000 U for 7 days and BCNU was given in doses of 200mg/sqm for 1 day, intravenously before postoperative radiotherapy and was repeated at the interval of 6 weeks. Survival rates were analyzed between our IBR therapy group and historical data of radiation therapy alone. Several prognostic factors were analyzed in the IBR therapy group. Survival curves were observed according to the Kaplan Meier method. Our observation revealed that IBR therapy showed encouraging results in some patients without stastistical significant in general. However, despite the above observtion, we believe that the statistical out come of the IBR group may change statistically if given a longer follow up period. Furthrmore, our study also demonstrated that the improved survival time gained from total resection over subtotal resection was statistically significant.

Effect of ACNU Chemotherapy on Malignant Glioma

In order to determine if there was an enhancing therapeutic effect of ACNU(1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride, nimustine chloride given in addition to radiotherapy, we performed a randomized clinical study of irradiation alone and combination of irradiation with ACNU in the treatment of malignant gliomas. Thirty-seven patients who were treated in our hospital from August 1990 to September 1992 were included in this study. An effect was defined as a statistically improved survival times. Radiotherpy with a total dose of 5000 to 6500 rads was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously at a dose of 1-2mg/kg. The survival rates of patients with anaplastic astrocytoma and glioblastoma multiforme at 18 months after the surgery were 0% and 37% for radiotherapy alone, and 66.7% and 40.1% for radiotherapy plus ACNU, respectively. The median survival times of patients with anaplastic astrocytoma and glioblastoma multiforme were 14 and 15 months for radiotherapy alone, and 19 and 16 months for radiotherapy plus ACNU, respectively. The survival rates of patients with malignant gliomas(anaplastic astrocytoma plus glioblastoma multiforme) at 18 months were 5.5% for radiotherapy alone and 45.4% for radiotherapy plus ACNU, and the median survival times were 15 and 16 months, respectively, Althouh the survival rate of patients with malignant gliomas at initial 6 months was much higher in radiotherapy plus ACNU than in radiotherapy alone, the differences between survival curves were not significant at the p=0.05 level. This study demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapapeutic regimen to prolong survival of patients with malignant gliomas.