Tracer transport and metabolism in a patient with juvenile pilocytic astrocytoma. A PET study

We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), ¹⁸ F-fluorodeoxyglucose (FDG),¹¹ C-methionine (MET), and ⁸²Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier transport rate constants and tracer distribution volume in the range of glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation of MET and FDG was increased. With regard to the known vascular composition of JPA, our data suggest that increased transport and distribution considerably contribute to the high net tracer uptake observed in this tumor.     

Reirradiation for recurrent cerebral astrocytoma

Summary We describe a case of reirradiation for symptomatic, recurrent, inoperable cerebral astrocytoma grade 11. Symptomatic and radiographic response were obtained with no evidence of radiation induced brain injury three years following reirradiation. The factors affecting radiation injury and indications for reirradiation are discussed. Repeat radiotherapy is a useful treatment option in selected patients with recurrent brain tumors.     

Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma

The incidence of hemorrhagic onset in pilocytic astrocytoma and pilomyxoid astrocytoma, and the clinical and histological characteristics, were compared to other types of neuroepithelial tumors or nonhemorrhagic pilocytic astrocytoma by retrospective review of 445 consecutive neuroepithelial tumors treated at our institute. Hemorrhagic onset was observed in 4 of 35 (11.4%) patients with pilocytic astrocytoma and pilomyxoid astrocytoma, with higher incidence than in glioblastoma (3.9%), anaplastic oligodendroglioma (7.7%), and anaplastic ependymoma (7.1%). The hemorrhagic onset occurred in 2 patients with sporadic pilocytic astrocytoma, 1 with pilocytic astrocytoma associated with neurofibromatosis type 1, and 1 with pilomyxoid astrocytoma. There was no correlation between hemorrhagic onset and clinical features, including age, sex, tumor location, proliferative activity, or microvascular proliferation. Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma is not as uncommon as was previously thought, so pilocytic astrocytoma or pilomyxoid astrocytoma should be considered in the differential diagnosis of patients with brain tumors manifesting as hemorrhagic onset.     

Survival and prognosis of patients with astrocytoma with atypical or anaplastic features

Summary This study confirms the importance of histologic tumor necrosis as a major prognostic variable in malignant glioma. Necrosis is present in glioblastoma multiforme (GBM), and absent in astrocytoma with atypical or anaplastic features (AAF). This paper evaluates 94 patients with AAF and 462 patients with GBM treated with radiation therapy with or without BCNU on 3 consecutive randomized protocols of the Radiation Therapy Oncology Group (RTOG) between 1974 and 1983. Multivariate analyses of the 556 patients confirmed histology as a significant independent variable that is prognostically relatively more important than Karnofsky performance status (KPS) and extent of surgery, and somewhat less important than age. The median survival for AAF was 36.2 months and for GBM was 8.6 months. In addition, separate multivariate analyses of AAf cases determined that the extent of surgery is a significant independent variable that is relatively more important than KPS, but less important than age. The median survival of AAF patients who underwent surgical excision was 46.8 months compared with 15.2 months for those biopsied (p < .001).Presented in part at the Second International Symposium on Biology of Brain Tumours, London, October 1984.     

Spinal astrocytoma with intracranial metastases

Summary We present a 21-year-old man with a spinal intramedullary astrocytoma in the low thoracic segment who died of multiple intracranial metastases more than 3 years after primary surgery.     

治疗135例脑恶性星形细胞瘤的探讨

目的 :分析脑恶性星形细胞瘤手术后采用单纯放射治疗及放疗加颈动脉化疗的疗效。材料与方法 :1987年 8月～ 1992年 11月收治 135例脑恶性星形细胞瘤。分两组治疗 ,单放组 71例 ,综合组 6 4例。两组放疗剂量 DT5 5～ 70 Gy。综合组术后 4～ 15天行颈动脉化疗 ,10～ 15天后行放疗 ,放疗结束再化疗 1～ 3次。结果 :单放组中位生存期 17.5个月 ,综合组为 31.9个月。其中效果最好的是多形性胶质母细胞瘤。33例中 2 ,3,5年生存率分别 70 %、36 %、15 %。结论 :脑恶性星形细胞瘤术后采用综合组治疗方案疗效满意     

Patient with resected anaplastic astrocytoma and an image suggestive of relapse

The main treatment of asctrocytomas is surgery, which serves a double purpose: diagnosis and treatment. Surgery can be complemented with radiotherapy. With respect to chemotherapy, there continues to be a controversy as to whether it has the capacity to overcome the blood-brain barrier. An interesting option has been the implantation of biodegradable polymers of carmustine that are placed in the cavity left by the surgical procedure. With respect to the cerebral edema that can be associated with the carmustine implants, there can appear images in follow-up that are suggestive of relapse.     

High-grade astrocytoma treated concomitantly with estramustine and radiotherapy

Summary Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt®) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22–87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3–92.7) months for the radiotherapy only group and 17.3 (0.4–96.9+) months for the estramustine  + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1–89.2) and 10.3 (0.3–91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.     

Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma

A retrospective study of bevacizumab only in adults with recurrent temozolomide (TMZ)-refractory anaplastic astrocytoma (AA) with a primary objective of determining progression free survival (PFS). There is no standard therapy for alkylator-resistant AA and hence a need exists for new therapies. Twenty-five patients (15 men; 10 women) ages 26–63 (median 50), with radiographically recurrent AA were treated. All patients had previously been treated with surgery, involved-field radiotherapy, and alkylator-based chemotherapy. Fourteen patients underwent repeat surgery. Patients were treated at second recurrence with bevacizumab (10 mg/kg), once every 2 weeks (defined as a single cycle). Neurological evaluation was performed every 2 weeks and neuroradiographic assessment following the initial two cycles of bevacizumab and subsequently after every four cycles of bevacizumab. All patients were evaluable for toxicity and response. A total of 360 cycles of bevacizumab (median 14 cycles; range 2–40) was administered. Bevacizumab-related toxicity included fatigue (14 patients; 2 grade 3), leukopenia (7; 1 grade 3), deep vein thrombosis (5; 2 grade 3), hypertension (5; 1 grade 3), anemia (4; 0 grade 3) and wound dehiscence (1; 1 grade 3). Sixteen patients (64%) demonstrated a partial radiographic response, 2 (8.0%) stable disease and 7 (28%) progressive disease following two cycles of bevacizumab. Time to tumor progression ranged from 1 to 20 months (median: 7). Survival ranged from 2 to 23 months (median: 9.0). 6-month and 12-month PFS were 60 and 20%, respectively. Bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent alkylator refractory AA.     

脑星形细胞瘤MRI定量参数评价血管内皮生长因子表达的价值

目的探讨MRI定量参数评价星形细胞瘤血管内皮生长因子(VEGF)表达强弱的可行性.方法收集手术病理证实的脑星形细胞瘤32例,计算MRI定量指标:T1WI、T2WI上的相对信号强度(RSI0)、增强后相对信号强度(RSIGd)及信号强度增加百分率(EP).采用免疫组化法标记VEGF,对照MRI定量参数与VEGF标记指数之间的关系.结果恶性组与偏良性组之间,上述MRI定量参数差异均有显著性;增强后相对信号强度(RSIGd)及信号强度增加百分率(EP)与VEGF呈正相关.结论增强后相对信号强度(RSIGd)及信号强度增加百分率(EP)可以较好地反映星形细胞瘤的VEGF表达强弱和病理分级.     

Imaging the pharmacokinetics of [F-18]FAU in patients with tumors: PET studies

Purpose: FAU (1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) uracil) can be phosphorylated by thymidine kinase, methylated by thymidylate synthase, followed by DNA incorporation and thus functions as a DNA synthesis inhibitor. This first-in-human study of [F-18]FAU was conducted in cancer patients to determine its suitability for imaging and also to understand its pharmacokinetics as a potential antineoplastic agent. Methods: Six patients with colorectal (n=3) or breast cancer (n=3) were imaged with [F-18]FAU. Serial blood and urine samples were analyzed using HPLC to determine the clearance and metabolites. Results: Imaging showed that [F-18]FAU was concentrated in breast tumors and a lymph node metastasis (tumor-to-normal-breast-tissue-ratio 3.7–4.7). FAU retention in breast tumors was significantly higher than in normal breast tissues at 60 min and retained in tumor over 2.5 h post-injection. FAU was not retained above background in colorectal tumors. Increased activity was seen in the kidney and urinary bladder due to excretion. Decreased activity was seen in the bone marrow with a mean SUV 0.6. Over 95% of activity in the blood and urine was present as intact [F-18]FAU at the end of the study. Conclusions: Increased [F-18]FAU retention was shown in the breast tumors but not in colorectal tumors. The increased retention of FAU in the breast compared to bone marrow indicates that FAU may be useful as an unlabeled antineoplastic agent. The low retention in the marrow indicates that unlabeled FAU might lead to little marrow toxicity; however, the images were not of high contrast to consider FAU for diagnostic clinical imaging.     

Analysis of pilocytic astrocytoma by comparative genomic hybridization

Very little is known about genetic abnormalities involved in the development of pilocytic astrocytoma, the most frequently occurring brain tumour of childhood. We have analysed 48 pilocytic astrocytoma specimens using comparative genomic hybridization. Only five of 41 tumours from children showed abnormalities detectable by comparative genomic hybridization, and in each case this represented gain of a single chromosome. Interestingly, two of seven tumours from adults showed abnormalities, which were multiple and relatively complex. Six of the seven tumours showing abnormalities were from female patients (two adults and four children). The most frequently detectable abnormality was gain of 9q34.1-qter, which was present in three cases (two adult and one paediatric).     

婴儿促纤维增生型星形细胞瘤1例并文献回顾

目的：探讨婴儿促纤维增生型星形细胞瘤病理形态特征及鉴别要点。方法：报道1例婴儿促纤维增生型星形细胞瘤并结合文献对其组织学和免疫组织化学特点进行研究。结果：本例婴儿促纤维增生型星形细胞瘤头颅CT表现为右侧额骨及顶骨局部骨质缺损，右侧大脑半球多囊性占位性病变。组织学表现为梭形肿瘤细胞，形似纤维细胞或纤维母细胞，排列呈束，编织样。免疫组织化学显示：瘤细胞呈胶质酸性蛋白（GFAP）阳性，波形蛋白（Vimentin）阳性，S-100蛋白阳性。结论：婴儿促纤维增生型星形细胞瘤是一种比较罕见的发生于婴幼儿的脑部肿瘤，根据其临床特点及组织学和免疫组织化学特征可以进行明确诊断。     

Intracranial astrocytoma with diffuse bone marrow metastasis: a case report and review of the literature

A 41 year old male presented with headache, lethargy, and ataxia and found to have a left temporal lobe mass and a leukoerythroblastic peripheral blood smear. The latter prompted an iliac crest bone marrow biopsy on which a diagnosis of metastatic glioma was made and verified by immunohistologic characterization. The patient was treated with cranial irradiation and simultaneous systemic BCNU (bis-dichloroethylnitrosurea) with complete response. This case with diffuse bone marrow involvement demonstrates that a glioblastoma is capable of extracranial metastases without previous intervention. From a review of reported cases of gliomas of extraneural metastasis, it is concluded that untreated gliomas are capable of vascular spread although less frequently than previously manipulated tumors.     

星形细胞瘤抗原处理相关转运蛋白异常表达的临床意义

目的:研究星形细胞瘤中抗原处理相关处理蛋白(TAP)分子表达及其临床意义,探讨星形细胞瘤的治疗对策。方法:采用免疫组织化学技术检测50例星形细胞瘤患者肿瘤组织和15例正常脑组织中TAP的表达。结果:50例星形细胞瘤患者中27例TAP蛋白表达阳性,23例TAP蛋白表达阴性,TAP蛋白阳性细胞百分率为29.1%±27.24%;正常组15例,全部表现为TAP蛋白表达阳性,TAP蛋白阳性细胞百分率为58.4%±21.69%,两组均数比较差异有统计学意义,t=3.8110,P<0.05。低级别星形细胞瘤(Ⅰ级和Ⅱ级)25例,TAP蛋白平均阳性细胞百分率为37.4%±29.13%;高级别星形细胞瘤(Ⅲ级和Ⅳ级)25例,TAP蛋白平均阳性细胞百分率为22.8%±20.08%;两组均数比较差异有统计学意义,t=2.0631,P<0.05。结论:星形细胞瘤患者存在TAP分子低表达,这可能促使星形细胞瘤患者肿瘤细胞逃避免疫监视,TAP蛋白缺失率可作为预测脑星形细胞瘤的发生及其恶性程度的指标之一。     

毛黏液星形细胞瘤的临床病理观察(英文)

Objective:The aim of this study was to study the clinicopathological and immunohistochemical features of pilomyxoid astrocytoma(PMA).Methods:The clinical and pathologic features in six cases of PMA were analyzed.Immunohistochemical staining for glial fibrillary acidic protein(GFAP),synaptophysin(Syn),Chromogranin A(CgA),cytokeratin(AE1/AE3),epithelial membrane antigen(EMA)and Ki67 was performed on paraffin-embedded sections.Results:Among the six cases,five occurred in female patients,one was male,the age at diagnosis ranged from 2 to 15 years.Four cases were located in the hypothalamic area and optic pathway,one case in the third ventricle,and one case in left parietal lobe.On imaging,PMAs often appears as well-circumscribed mass.Microscopically,the tumor was composed of monomorphous bipolar(piloid)cells setting in a prominent myxoid background with an angiocentric radiating growth pattern in some areas.PMA lacked biphasic pattern,Rosenthal fibers and eosinophilic granular bodies which were usually typical in a classic pilocytic astrocytoma(PA).Immunohistochemcal study showed that the tumor cells were diffusely positive for GFAP.Syn positive staining was observed in one case.The Ki67 labeling index measured less than 5%.Conclusion:PMA is a distinct aggressive variant of pilocytic astrocytoma with special histological and immunohistochemical features.It is typically a rare tumor of early childhood.Immunohistochemical staining for GFAP and Syn is helpful in differential diagnosis.     

18F-FDG PET/CT在探测卵巢癌术后复发和转移中的价值

[目的]评价^18F-FDG PET/CT显像在探测卵巢癌术后复发病灶中的应用价值。[方法]采用仪器为Siemens Biograph Sensation 16 PET/CT，43例卵巢癌术后患者禁食4～6h，静脉注射^18F-FDG60min后进行PET/CT检查，采集方式为3D模式。PET/CT图像结果与血清CA125、B超及CT或MRI影像学资料进行比较。并与手术病理或临床随访结果比较判断其诊断的准确性。[结果]FDG PET/CT诊断卵巢癌复发的灵敏度、特异性和准确性分别为92.3%、100%和93.0%。血清CA125水平与FDG PET结果有一定相关性，33例CA125升高患者中31例PET显像阳性，10例CA125正常水平患者中仅有5例PET显像阳性。[结论]当常规影像学检查阴性或可疑时，PET/CT显像对卵巢癌复发的检测具有较高的灵敏度和准确性，特别术后患者CA125升高的情况下，FDG PET/CT有助于探测隐匿性复发或转移病灶，指导进一步的治疗。