Accumulation of genomic aberrations during clinical progression of medulloblastoma

Medulloblastomas comprise the most frequent malignant brain tumor in childhood and one of the biggest challenges in pediatric oncology. The current concept suggests that these tumors may undergo stepwise progression as it has been shown for other brain tumors. However, conclusive evidence of molecular progression over time has not been demonstrated yet for medulloblastoma. In the present study, 28 pairs of medulloblastoma at primary diagnosis and at the time of recurrence, either occurring as local tumor regrowth or tumor dissemination, were histopathologically and molecularly analyzed. Cytogenetic analysis included interphase fluorescence in situ hybridization for five genomic loci (MYC, MYCN, 17p, 17q, 6q) that have previously been identified as prognostic markers in primary tumors. Of 16 tumors showing early recurrence (<4 years after first diagnosis), only one showed increased histological anaplasia in the secondary lesion (6%), and two acquired genomic lesions indicative for a more malignant phenotype (13%). In contrast to this, of 12 tumors with a time to recurrence of 4 years or more, nine tumors (75%) showed a more malignant phenotype either reflected by increased anaplasia alone or by both increased anaplasia and acquirement of genomic aberrations known to be associated with inferior patient outcome. These results suggest that early recurrence in medulloblastoma mainly occurs in tumors with a highly malignant genotype and phenotype per se, whereas late recurrence is often dependent on tumor evolution toward a more malignant biology. Therefore, biopsy of recurrent tumors should be performed to assess the biologic properties of the relapsed tumor, especially when targeted therapy approaches are considered.     

Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia.

The 50 patients in this survey were classified by a panel of neurologists into 4 clinical sub-groups: Group Ia ("typical" Friedreich's ataxia, complete picture), Group Ib ("typical" Friedreich's ataxia, incomplete picture), Group IIa ("atypical" Frriedreich's ataxia, possible recessive Roussy-Levy syndrome), Group IIb (heterogeneous ataxias). The clinical symptoms and signs were analyzed for each of these groups. A constellation of signs constantly present in Friedreich's ataxia and obligatory for diagnosis was described. Other important symptoms, such as the Babinski sign, kyphoscoliosis and pes cavus were found to be progressive, but not essential for the diagnosis at any given time. Finally, a host of other symptoms can only be called accessory. The progression of scoliosis was found to be an important tool in the differential diagnosis of ataxias. Our study also indicates, in contrast to the opinion of some authors, that absent deep tendon reflexes in the lower limbs and early dysarthria are essential in "typical" Friedreich's ataxia.     

多学科诊疗门诊在神经肿瘤病例中的诊治效率评估

目的探讨多学科诊疗（MDT）在神经肿瘤中的诊治效率。 方法回顾性分析2019年6月至2020年6月于深圳市第二人民医院神经外科疑难神经肿瘤MDT门诊就诊的49例患者的临床资料。所有患者MDT诊疗前由专科诊疗小组讨论制订可能的诊治方案，并与MDT后的诊治方案进行比较，分析诊断和治疗上的改变情况。这些诊断和治疗指标的改变根据文献报道标准进一步分为主要改变和次要改变两类。分析MDT前后诊断和治疗指标的改变种类和改变比例。 结果诊断方面，MDT前后未发生改变的患者33例（67.3%），发生改变的16例（32.7%），其中符合主要改变的7例（14.3%），符合次要改变的9例（18.3%）。治疗方面，MDT前后未发生改变的26例（53.1%），发生改变的23例（46.9%），其中符合主要改变的15例（30.6%），符合次要改变的8例（16.3%）。不同神经肿瘤类型对MDT前后诊断和治疗的改变率、改变程度的影响，差异均无统计学意义（P>0.05）。复发肿瘤患者MDT前后治疗指标发生改变的比例较初发者高，且主要改变比次要改变占比高，差异均具有统计学意义（P<0.05）。同时，复发胶质瘤患者MDT前后治疗发生改变比例较初发胶质瘤者高，差异有统计学意义（P<0.05）。 结论不同肿瘤类型的MDT效率无差别，但复发肿瘤MDT前后修正效率差异明显。复发性的神经肿瘤疾病由于诊断和治疗的复杂性，更需要MDT的介入。     

Recurrent low-grade glioma in children with special reference to computed tomography findings and pathological changes

Recurrent low-grade gliomas in children were studied with special reference to correlation between the computed tomography (CT) scan and pathological findings at recurrence. During the past 16 years (1970–1986) 105 cases of primary pediatric brain tumors were treated in our hospital. Seventeen of these had low-grade glioma, seven of which (five astrocytomas, one ependymoma, and one subependymoma) had recurrence of tumor by the end of 1987. The enhanced CT findings were classified into three types — cystic, false cystic, and solid, according to Lapras' classification. The pathological findings of recurrent tumors were reviewed with particular attention to malignant transformation. The results showed that in two out of three cases where CT findings had changed from initial cystic to solid type at recurrence malignant transformation was revealed. Enhanced CT scan was also useful for detecting small asymptomatic recurrent tumors in children. On the other hand, surgical procedures and adjuvant therapies demonstrated no significant relationship with recurrence. It is suggested that the recurrence of low-grade glioma in children is not rare, and that changes in findings on contrast enhanced CT might reflect malignant transformation in a recurrent tumor, necessitating a careful follow-up.     

Positron emission tomography imaging of brain tumors

A wide variety of metabolic features of brain tumors can be imaged using PET, including glucose metabolism, blood flow, oxygen consumption, amino acid metabolism, and lipid synthesis. Currently, FDG is the most widely available PET tracer for body imaging and brain imaging. Malignant brain tumors, like many other soft tissue tumors, show increased glucose metabolism, which is reflected on FDG-PET imaging. FDG-PET imaging of brain tumors provides information on tumor grade and prognosis. Compared with other organ systems, FDG-PET imaging of the brain presents unique challenges because of the high background glucose metabolism of normal gray matter structures. Coregistration of the MRI (or CT) and FDG-PET images is essential for accurate evaluation of brain tumors and is performed routinely at the authors' institution. The heterogeneous nature of gliomas can result in significant sampling errors when patients are biopsied for primary tumor diagnosis or recurrent disease. FDG-PET can be used to define the most metabolically active targets for stereotactic biopsy. This in turn can improve diagnostic accuracy and reduce the number of biopsy samples required. FDG-PET is also useful for evaluating residual or recurrent tumor following therapy, and can be used to survey patients with low-grade brain tumors for evidence of degeneration into high-grade malignancy. In the case of suspected tumor recurrence or progression, PET can aid in defining appropriate targets for biopsy. One limitation of FDG-PET is the occasional inability to distinguish radiation necrosis from recurrent high-grade tumor. A second limitation is that FDG-PET is less sensitive than contrast-enhanced MRI for detecting intracranial metastases, and it is the authors' experience that brain studies should not be included as part of routine whole-body PET studies. Other tracers, such as 11C-methionine and FCH, also avidly accumulate in brain tumors and have the advantage of low background cortical activity. The relationship between degree of uptake of these agents and tumor grade is not established. These tracers may be useful in specific clinical situations, however, such as tumor localization for treatment planning or evaluation of low-grade tumors.     

TET2 promotor methylation and TET2 protein expression in pediatric posterior fossa ependymoma

Pediatric posterior fossa ependymoma (PF) is one of the most common brain tumors in children. Recently, two subtypes of PF were identified. PF-A has a dismal prognosis and shows a hypermethylation phenotype, whereas PF-B shows a great genomic instability. The ten-eleven translocation methylcytosine dioxygenase 2 (TET2) gene (TET2) has been linked to the regulation of DNA methylation. We analyzed TET2 promotor methylation and protein expression to assess the role of TET2 in PF. Medical records of all PF cases treated in our institution between 1993 and 2015 were evaluated regarding tumor histology, grade, tumor location, gender, age, tumor recurrence, distant metastasis, survival and time to progression. Subsequently, we analyzed TET2 promotor methylation using methylation-specific polymerase chain reaction. TET2 protein expression was assessed using immunohistochemistry. Low TET2 expression was detected in seven of 17 cases. There was an association between low TET2 expression and tumor recurrence (P = 0.049). A TET2 promotor methylation was detected in five of 10 cases. There was no association between the TET2 promotor methylation with recurrence, tumor grade or gender. TET2 promotor methylation and low TET2 expression was detected in a subgroup of PF. Our data show an association between low TET2 expression and tumor recurrence in PF.     

scRNA-seq and proteomics reveal the distinction of M2-like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

Aims

Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2-like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.

Methods

We employed single-cell RNA sequencing to construct a single-cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.

Results

Six subgroups of TAMs were annotated and M2-like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up-regulation of several cancer pathways and intercellular interaction-related genes are associated with the recurrence of malignant glioma. Moreover, the M2-like TAMs can activate the PI3K/Akt/HIF-1α/CA9 pathway in the malignant glioma cells via SPP1-CD44-mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.

Conclusion

Our study uncovers the distinction of M2-like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.     

Local versus diffuse recurrences of meningiomas: factors correlated to the extent of the recurrence

OBJECTIVE: The aim of this study is to evaluate the factors correlated with the different patterns (local, peripheral and diffuse) of meningioma recurrence. MATERIAL AND METHODS: 55 patients with benign (WHO I) meningiomas which recurred after seemingly complete removal were reviewed; 40 (Group I) had local or peripheral recurrences (< 3 cm from the initial dural attachment) and 15 (Group II) had distant and diffuse recurrences. Patient age and sex, tumor location, interval of recurrence, tumor shape, type of brain-tumor interface, histological subtype, mitotic index (MI) and progesterone receptor (PR) expression of the initial tumor, histological WHO Grade of the recurrent tumor and patient outcome were analyzed and correlated with the pattern of recurrence. RESULTS: Flat-shaped meningiomas with large dural attachment showed a significantly higher rate of diffuse recurrences than round tumors, whereas the brain-tumor interface and the tumor location were not relevant (excepting the lack of convexity meningiomas in the group of diffuse tumors). There were no significant differences of histology, MI and PR expression of the initial tumor and histological grade of the recurrent tumor between the two groups. CONCLUSIONS: The different patterns of meningioma recurrences (local, peripheral, diffuse) are not correlated with the tumor location and histology and do not represent a different biological tumor progression. We agree that most unexpected extensive recurrences result from a more extensive microscopic dural involvement.     

A clinicopathological study of the significance of the proportion of choroid morphology in chordoid meningioma

Chordoid meningiomas (CM) account for approximately 0.5% to 1.0% of intracranial meningiomas. This tumor has a strong risk of recurrence and aggressive growth (World Health Organization grade II). Histological analysis of CM tumors shows that the tissue is often dominated by chordoid morphology; however, the exact relationship between the percentage of the chordoid component and other clinicopathological features is unknown. We collected 26 surgical specimens from 17 patients who had a histological diagnosis of CM between January 1986 and June 2010. The chordoid elements constituted 30% to 98% of the area of the tumor. In 12 of 17 (70.6%) primary tumors, over 50% of the area displayed the chordoid pattern. Recurrence was noted in nine of these patients and five underwent a second operation. These five patients showed a histopathological progression of aggressive features. The proportion of chordoid elements in each recurrent tumor also increased. Thus, the chordoid proportion in CM is associated with a greater likelihood of recurrence.     

Spinal cord tumors in children under the age of 3?years: a retrospective Canadian review

Background

Tumors of the spinal cord are exceedingly rare in infancy and only a paucity of literature exists describing the spectrum of this disease and its management. The objectives of our study were to describe the demographic characteristics of spinal cord tumors (SCT) in children less than 3?years of age at diagnosis and to review their treatment and outcome.

Methods

A national retrospective chart review was conducted on patients under the age of 3?years diagnosed with a primary tumor of the central nervous system (CNS) between 1990 and 2005 across Canada. Inclusion criteria were: age ??3?years, histologic confirmation of the diagnosis, and residency in Canada. A centralized database was created and information regarding SCT was extracted.

Results

Twenty-five of five hundred seventy-nine patients (4.3%) in the data bank had a SCT. The majority of tumors were low-grade astrocytomas (14/25). Leptomeningeal dissemination based on neuroradiologic imaging and/or cerebrospinal fluid cytology was present in five (20%) patients. The majority of patients underwent an incomplete surgical resection (52%). Most patients (64%) did not receive postoperative radiotherapy or chemotherapy. Seventy-two percent (18/25) developed recurrent/progression of disease. Overall 2- and 5-year survival for low- and high-grade malignancies was 93?±?6.4% and 37.5?±?17.1% respectively. Significant predictors of survival included mean duration of symptoms prior to initial diagnosis and recurrence/progression of disease.

Conclusions

Relapse/progression of disease in infant SCT is frequent. Prolonged survival of low-grade tumors is possible with further therapy; however, the prognosis of high-grade malignancies remains poor.     

Molecular genetic alterations in pleomorphic xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA) is a low-grade glioma that may recur as a malignant diffuse astrocytoma such as glioblastoma (GBM). While the molecular genetic basis of diffuse astrocytomas has been studied extensively, PXAs have not been analyzed in detail. We, therefore analyzed DNA from archival primary and recurrent PXAs from eight patients (three grade II PXAs without recurrence, one grade II PXA with recurrence as grade II PXA, two grade II PXAs with progression to GBM, and two grade III anaplastic PXAs with recurrence as grade III anaplastic PXA or GBM) for genetic changes associated with diffuse astrocytomas. Single-strand conformation polymorphism analysis of p53 exons 5–8 revealed migration shifts in two cases, one primary PXA without recurrence and one recurrent grade II PXA in which the primary tumor did not show a shift. DNA sequencing showed two missense mutations in codons 220 (exon 6) and 292 (exon 8), respectively, mutations which have not been previously noted in astrocytomas. Differential polymerase chain reaction analysis demonstrated epidermal growth factor receptor gene amplification in only one tumor, a GBM without allelic loss of chromosome 10 that was the second GBM recurrence of an initial grade II PXA. Loss of heterozygosity studies on tumors from five patients, using three microsatellite polymorphisms on chromosome 10q and three on chromosome 19q, did not disclose allelic loss in any recurrent tumor. These findings suggest that the genetic events that underlie PXA formation and progression may differ significantly from those involved in diffuse astrocytoma tumorigenesis. Received: 18 July 1995 / Revised, accepted: 15 September 1995     

椎管内复发肿瘤的诊断和手术治疗(附28例报告)

目的　研究复发椎管内肿瘤的临床诊断和手术治疗特点。方法　对 2 8例复发椎管内肿瘤进行回顾性分析 ,所有患者均用MR诊断并再次行手术治疗。结果　 2 8例复发椎管内肿瘤诊断明确 ;出院时 ,症状体征改善或消失者 2 1例 ,无变化 6例 ,加重 1例。 18例随访 2个月至 9年 ,症状体征继续改善者 15例 ,无变化 2例 ,死亡 1例。结论　根据临床表现及MR检查即能明确诊断复发椎管内肿瘤 ;只要提高手术技能 ,复发椎管内肿瘤的手术疗效仍然是令人满意的     

Clinical aspects of molecular biology of pituitary adenomas

Pituitary adenomas are primary, benign CNS tumors. Sporadically, they metastasize or become malignant. However, they can infiltrate adjacent structures even if they are benign and without hormonal activity. Moreover, by compressing adjacent tissues they cause their gradual degradation and, as a result, irreversible CNS damage. Pure endoscopic transnasal transsphenoidal approach enables minimally invasive resection of the aforementioned tumors. In most cases, standard total resection is sufficient but in some cases tumors could be recurrent. There are still unknown risk factors leading to recurrence and subsequent progression of these tumors. This is the reason why pituitary adenomas are a serious clinical and social problem in spite of their benign histology. Continuous development of immunohistochemical and proteomic examinations and application of advanced methods of functional genomics allow for better understanding of biology and pathogenesis of these tumors. In the paper authors discuss molecular etiopathogenesis of pituitary adenomas.     

Positron emission tomography and perfusion weighted imaging in the detection of brain tumors recurrence: A meta-analysis

Objectives:To assess and compare the diagnostic accuracy, sensitivity and specificity of perfusion-weighted imaging (PWI) and positron emission tomography (PET) in distinguishing between treatment-related changes and tumor recurrence.Methods:We carried out a systematic review of PubMed, Embase, Web of Science, the Cochrane Library, and CINAHL databases from database inception until August 2021 for pertinent articles. Particular inclusion and exclusion criteria were applied to select the eligible studies. The Quality Assessment of Diagnostic Accuracy tool was used to assess the risk of bias and methodological quality of the eligible studies. From the included studies, the rate ratio (RR) of pooled accuracy, sensitivity, specificity and their corresponding confidence intervals (CIs) were estimated for both PWI and PET.Results:The systematic review and meta-analysis comprised 14 research studies, with a total of 542 patients. Although PET revealed a moderately higher accuracy and sensitivity when compared to PWI (RR: 0.94, 95% CI 0.86-1.02 and RR: 0.95 95% CI 0.85-1.06, respectively), the difference was not statistically significant (p>0.05). Similarly, while PWI demonstrated a moderately higher specificity when compared to PET (RR:1.10, 95% CI 0.98-1.23) but. However, no statistically significant difference between the 2 modalities was detected (p>0.05). Interestingly, we revealed that 18F-FET-PET was significantly more efficient than PWI in terms of accuracy (RR: 0.82, 95% CI 0.72-0.93) and sensitivity (RR: 0.72, 95% CI 0.62-0.83) (p>0.05).Conclusion:Both PET and PWI yielded good diagnostic performance in distinguishing treatment-related changes from tumor recurrence, and neither modality seemed to be superior. PROSPERO ID: CRD42021288160

Brain tumors occur when abnormal and uncontrolled cell division appears in the brain. Nowadays, non-cancerous (benign) tumors and cancerous (malignant) tumors are the 2 groups of tumors recognized worldwide. ¹ Brain tumors can also be categorized as primary tumors, starting in the brain, and secondary tumors, also known as brain metastasis tumors, which most frequently have spread to the brain from primary tumors in other organs. ² The Central Brain Tumor Registry of the United States reported that primary brain tumors account for around 2% of all cancers, while metastases occur approximately in 10-20% of people with cancerous tumors and are 10 times more frequent than primary brain tumors. ³ The annual frequency of primary brain tumors can reach 19 cases per 100,000 people. The incidence is 3 cases per 100,000 people at less than 4 years of age. The prevalence decreases between 15 and 24 years of age and then increases regularly to a peak of 19 cases per 100,000 people between 65 and 79 years of age. ⁴ The World Health Organization (WHO) classifies brain tumors into different types, and each of them may be classified into diverse grades, including neuroepithelial and non-neuroepithelial tumors. ⁵ The majority of primary tumors of the brain in adulthood are gliomas, with a prevalence of 45% among all brain tumors and 90% of primary brain tumors in elderly patients. ⁶ Gliomas are classified into 4 grades (I, II, III, and IV) based on the WHO classification. Low-grade gliomas include grades I and II, while high-grade gliomas include grades III and IV. The grade IV glioma is also known as glioblastoma multiforme. ⁷ Many studies have demonstrated a higher prevalence of brain cancer in developed countries. Furthermore, the prevalence of brain cancer depends on many factors, such as age, gender, and race. Meningioma and glioblastoma are mostly detected at approximately 65 years of age. However, the other types of brain tumors, such as pilocytic astrocytoma, germ cell, and pineal region tumors are detected at an early age. ⁸ The prevalence of brain tumors is moderately greater in men as compared to that in women, but meningeal tumors seem to be 2 times as frequent among women. Regarding gliomas, their incidence is higher in men (7.7/100,000) as compared to that in women (5.61/100,000). ⁹ The prevalence of primary brain tumors is higher in Asian, white, and black populations with regard to American and Indian Native race groups. Brain cancers have a 5-year survival rate of approximately 33%. In general, high performance status, young age, and low histopathological grade are positive prognostic characteristics for primary brain tumors. ¹⁰ Therapeutic options are dependent upon the kind of brain tumor, as well as its location and size. Treatments for brain tumors include surgical resection of solitary lesions, stereotactic brain surgery and radiation with or without chemotherapy. ¹¹ Treatment-induced necrosis is a frequent treatment-related condition occurring during the treatment of gliomas, which is usually detected 3 to 12 months post-treatment. ¹² Indeed, after high radiation doses, patients usually develop constant or continuous enhancement detected with recurrent tumors (pseudoprogression), radionecrosis and inflammation. These conditions mimic tumor progression or recurrence after remission. ¹³ Pseudoprogression appears as an increase in the size of the primary tumor or the appearance of a new lesion, thus resembling early progressive tumors. ¹⁴ It is evident that misdiagnosis of recurrent brain tumors changes the treatment strategy, which leads potentially to unnecessary repeat surgery or non-effective second-line treatment. ¹⁵ Histopathologic technique is the current gold standard to confirm the diagnosis of recurrent brain tumors, but biopsy is dangerous, with many adverse impacts (such as inflammation and hemorrhage). ¹⁶ Hence, differentiating tumor recurrence from other types of treatment-related changes is challenging. Consequently, valid, effective and non-invasive imaging techniques are required to improve the post-treatment surveillance of patients.Due to the disadvantages of histopathology, diverse neuroimaging techniques have been developed for the distinction of recurrent tumors from treatment-related changes. Magnetic resonance imaging (MRI) modalities, such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), and nuclear modalities, including positron emission tomography (PET), which can be associated with computed tomography (PET-CT) or magnetic resonance imaging (PET-MRI), are usually used for this purpose. ¹⁴ Nowadays, MRI is the standard neuroimaging modality for follow-up after treatment. ¹⁵ Standard MRI is based on the magnetization properties of atomic nuclei. The most common MRI sequences are T1-weighted and T2-weighted scans. ¹⁷ Even with the perfect ability to diagnosis brain tumors, the conventional MRI presents some limitations regarding the distinction between tumor recurrence and non-specific changes, which is especially relevant after therapy.To surmount these deficiencies, PET based on radioactive amino acids and PWI are suggested as alternative modalities that may supply supplementary pathophysiological evidence to standard MRI. Perfusion-weighted imaging is one of the most broadly used clinical techniques. It is accurate, reliable, and safe, as well as radiation-free. There are 3 types of PWI-dynamic magnetic contrast-enhanced, dynamic contrast-enhanced, and arterial spin labeling. ¹⁸ In recent years, PET using radioactive amino acids has been considered a very pertinent modality and is described as clinically helpful for managing patients with brain tumors. ¹⁹ Different types of radioactively labeled tracers (such as, 11C-MET, ¹⁸ F-FDG [fluorine18-fluorodeoxyglucose], ¹⁸ F-FLT [fluorothymidine], or ¹⁸ F-FET [fluorine-fluoro-ethyl-tyrosine]) are injected with PET to improve the detection of recurrent brain tumors. ²⁰ The first radiopharmaceutical tracer to be developed was ¹¹ C-methyl-L-methionine (MET), and ¹⁸ F-FDG is the most broadly applied tracer. ²¹ Nowadays, both of them are considered the best tracers for PET imaging of brain tumors. ²² In summary, imaging findings from PWI and PET may contribute, in addition to MRI, to improve both diagnostic and therapeutic planning, particularly in clinically challenging situations. However, each of these modalities has its disadvantages. Standard MRI does not produce reliable data to distinguish radiation-related changes from true tumor progression, while Magnetic resonance (MR) spectroscopy and PET can provide false positive results regarding recurrent tumors. ²³ Despite their significant contribution to better differentiate recurrent tumors from treatment-related conditions, research comparing the effectiveness of PET and PWI is limited.Therefore, this systematic review and meta-analysis was carried out to evaluate the diagnostic performance of PWI compared to PET for distinction between tumor recurrence and treatment-related changes. Then, we performed a subgroup analysis to investigate the effectiveness of each PET modality and tracer in comparison with PWI.     

神经内镜经鼻入路手术治疗颅咽管瘤的疗效评价

目的探讨神经内镜经鼻入路手术治疗颅咽管瘤的临床疗效。方法回顾性分析2018年10月至2020年4月首都医科大学附属北京天坛医院神经外科采用神经内镜经鼻入路治疗102例颅咽管瘤患者的临床资料,其中原发肿瘤82例,复发肿瘤20例。术后每3个月门诊随访患者的视力、视野,评估垂体-靶腺轴损伤数量以及有无尿崩症,复查头颅MRI观察肿瘤有无复发、进展。根据术后3个月的头颅MRI结果,评估肿瘤的切除程度结果102例患者中,92例(90.2%)肿瘤全切除,10例(9.8%)次全切除;其中原发肿瘤全切除77例,复发肿瘤全切除15例术后5例患者发生脑脊液漏并行神经内镜经鼻修补术,3例患者发生中枢神经系统感染。无一例患者死亡或出现昏迷。102例患者随访时间的中位数(范围)为12(6~19)个月。至末次随访,96例术前视力、视野受损的患者中,62例视力明显改善,27例稳定,7例恶化;术前视力正常的6例患者中,仅1例术后视力短暂下降,术后3个月复查时视力恢复正常。99例合并尿崩症,其中72例尿崩症持续时间≤3个月,27例持续时间>3个月至末次随访,73例术前存在垂体-靶腺轴功能障碍的患者,垂体-靶腺轴功能均无改善;29例术前垂体-靶腺轴功能正常的患者中,22例出现垂体-靶腺轴功能障碍102例患者随访期间复查头颅MRI均未见肿瘤复发或进展。结论采用神经内镜经鼻入路手术可更充分地观察肿瘤与视神经、垂体柄及下丘脑等结构的界限,为术者提供更清晰的术野,肿瘤全切除率较高,部分患者术后视力、视野改善,但术后尿崩症和垂体-靶腺轴功能障碍发生率较高。     

缺血性脑卒中复发与阿司匹林抵抗的相关性研究

目的观察缺血性脑梗死初发以及复发患者阿司匹林(ASP)疗效,探讨缺血性脑梗死复发与阿司匹林抵抗(AR)的关系,并对复发患者的危险因素进行相关性分析。方法采用回顾性研究方法,将急性缺血性脑梗死患者分为初发组和复发组,复发组入院后即行血栓弹力图(TEG)检测,初发组规律服用ASP后1 m进行TEG检测,比较初发组及复发组AR发生率。并对患者生化指标、TOAST分型及危险因素等进行Logistic回归分析,探讨缺血性脑梗死复发的临床相关因素。结果初发组AR发生率为28.57%;复发组AR发生率为56.76%。复发组AR明显高于初发组(P0.01)。糖尿病、冠心病在复发组出现率高(P0.05);年龄、性别、吸烟、饮酒、高血压、高脂血症、动脉粥样硬化型、BMI、TG、CHOL、LDL、HDL、HCY及hs-CRP的水平两组差异无显著性(P0.05)。对P0.1危险因素的Logistic回归分析示AR、糖尿病与缺血性脑梗死复发明显相关。结论 AR能显著增加缺血性脑梗死复发风险;糖尿病增加缺血性脑梗死复发风险。     

Spinal metastasis of gliosarcoma: Array-based comparative genomic hybridization for confirmation of metastatic spread

We report a 64-year-old woman who underwent craniotomy and gross total resection of a left frontal lobe tumor initially diagnosed as glioblastoma. Multiple wound revisions were necessary due to repeated wound healing disorders under concomitant radio-chemotherapy. After 9 months there was local cranial tumor recurrence, requiring re-operation. Thereafter, temozolomide monotherapy was implemented. Histologically, a shift from glial to mesenchymal differentiation was observed in the recurrent tumor, resulting in the diagnosis of gliosarcoma. A further 9 months later a thoracic spinal tumor occurred requiring emergency tumor resection. Analysis showed a mesenchymal tumor without definite glial component. Being resistant to local radiation therapy, symptomatic local spinal tumor progression was observed within 1 month requiring re-resection. There was no response to chemotherapy with bevacizumab and irinotecan. Considering the pronounced sarcoma-like differentiation, a sarcoma chemotherapy regime with doxorubicin was initiated. This was also to no avail; the disease progressed and recurred at both the spinal and cerebral locations, respectively. This ambiguous tumor characteristic and therapy resistance encouraged us to retrospectively perform molecular and array-based comparative genomic hybridization (aCGH) analysis on the extirpated cerebral and spinal tumors. Tumors from both locations showed a consistent cytogenetic signature of gain of chromosome 7, and losses of chromosomes 10 and 13. This novel report of aCGH analysis of spinal gliosarcoma metastasis and the correlation to the clinical disease course shows that genotypic profiling may serve as a supplementary diagnostic tool in improving our knowledge of the biologic behavior of rare tumor variants.     

分化型甲状腺癌术中喉返神经显露及不同腺叶切除对喉返神经及甲状旁腺功能的影响

目的 探究分化型甲状腺癌甲状腺全切术中喉返神经显露及不同腺叶切除对喉返神经及甲状旁腺功能的影响.方法 研究对象选取2014-01-2016-09收治的分化型甲状腺癌患者75例,依照随机数表法将其分为A,B,C3组,每组各25例.3组均予以甲状腺全切除术及单侧中央区淋巴结清扫治疗,A组未显露喉返神经,B组采取精细化被膜解剖结合环甲隙显露喉返神经法切除腺叶,C组采取常规术式结合甲状腺下动脉下路喉返神经法切除腺叶.对比3组手术情况、术后血清相关分子水平及不良反应发生率.结果 A组手术时间明显长于B、C组,差异具有统计学意义(P<0.05),而3组患者在术中出血量、淋巴结清除个数及意识恢复时间差异均无统计学意义(P>0.05).术后1、4、7 d B组患者的甲状旁腺激素水平与钙离子水平均明显高于C组,而C组亦明显高于A组,比较差异均具有统计学意义(P<0.05).B、C组不良反应发生率明显低于A组,差异具有统计学意义(P<0.05).结论 喉返神经显露及精细化被膜解剖腺叶均可降低喉返神经损伤率及甲状旁腺功能的损伤,值得临床推广.     

Prolonged survival in adult neurofibromatosis type I patients with recurrent high-grade gliomas treated with bevacizumab

Astrocytic tumors, especially optic pathway pilocytic astrocytomas, are common in pediatric NF1 patients. High-grade gliomas (HGGs) appear to be rare in adult and pediatric NF1 patients. This is a series of five consecutive, adult NF1 patients with recurrent HGGs treated at The University of Texas MD Anderson Cancer Center. Four patients met consensus clinical criteria for NF1 and one patient had presumed segmental NF1. Three patients had glioblastomas, one gliosarcoma, and one progressive, enhancing optic pathway glioma which was not biopsied. Two tumors had molecular testing performed; both were IDH wild type and activating oncogene mutations (1 BRAFV600E and 1 PIK3CA mutation) were found in these tumors. All five patients received bevacizumab-containing regimens at tumor recurrence. The median number of 4-week cycles of bevacizumab was 20. All five patients experienced prolonged post-recurrence survival following bevacizumab treatment ranging from ten to 72 months. The median overall survival from HGG diagnosis was 72.6 months with three patients alive and progression free at last follow-up. Three out of five patients developed vascular complications leading to bevacizumab discontinuation. In this case series, adult NF1 patients with recurrent HGGs had prolonged, post-recurrence survival after treatment with bevacizumab-containing regimens. Based on these results, further study of antiangiogenic therapy in NF1 patients with HGGs and bevacizumab-response in sporadic HGG patients with NF1-mutated tumors is warranted.