Glioma

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Background and Aim: Gliomas are the most common type of brain tumor in the world. Surgical resection is one of the most effective therapeutic methods in terms of patient prognosis. However, it is difficult for neurosurgeons and health-care providers to select which imaging technology to best support the procedure. These technologies included intraoperative magnetic resonance imaging (iMRI), intraoperative ultrasound (iUS), fluorescence guidance with 5-aminolevulinic acid (5-ALA), and intraoperative neuronavigation. Hence, in this study, we compared the gross total resection (GTR), postoperative complications within or outside of the central nervous system, and postoperative clinical improvement by multiple meta-analyses, which allows the integration of data through direct and indirect comparisons.Materials and Methods: The PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, and WanFang databases were searched for publications before April 2018. Randomized controlled trials, two-arm and three-arm prospective studies, and retrospective studies in patients who underwent surgical treatment for glioma were included. The most important outcome measures were the rates of GTR, postoperative complications, and clinical improvement. Results: In terms of GTR, iMRI (odds ratio [OR] = 5.70, 95% confidence interval [CI]: 3.40–9.60), iUS (OR = 2.70, 95% CI: 1.10–6.90), 5-ALA (OR = 2.40, 95% CI: 0.64–8.90), and neuronavigation (OR = 1.90, 95% CI: 1.20–3.10) were found to be more effective than conventional surgery. In addition, iUS (OR = 0.15, 95% CI: 0.04–0.52), iMRI (OR = 0.24, 95% CI: 0.14–0.43), and neuronavigation (OR = 0.34, 95% CI: 0.18–0.56) were more found to result in fewer complications than conventional surgery. Furthermore, patients' clinical improvement was better with iMRI (OR = 8.10, 95% CI: 3.00–25.00), iUS (OR = 4.90, 95% CI: 0.76–33.00), and neuronavigation (OR = 2.60, 95% CI: 1.00–7.20) than with conventional surgery. Conclusions: The developed ranking probability table indicated that iMRI was superior in terms of the GTR and clinical improvement, while iUS was the least likely to result in postoperative complications. Hence, it was concluded that iMRI or iUS is the most advantageous imaging modality.

Background and Aim: Glioblastoma multiforme (GBM) is a World Health Organization (WHO) Grade IV malignant tumor with astrocytic differentiation. Despite medical advances over the past few decades, the life expectancy of patients with GBM has remained relatively unchanged 8–12 months. There are two proposed mechanisms for the development of GBM – a natural progression of lower WHO-grade astrocytoma and de novo development. Both theories, however, center on neural progenitor cells in the central nervous system. The aim of this study was to evaluate the significance of CD34 neural stem cell progenitors in GBM. Materials and Methods: Fourteen cases (eight males and seven females, age 16–74 years) of tumors with astrocytic differentiation were evaluated using the automated immunohistochemistry detection algorithm of Qupath v0.2.0-m4. Due to CD34 marking not only neural progenitors but also endothelial cells, the tumors were evaluated over an area of 76 mm^[2], with blood vessels excluded from the analysis. In superficial tumors, again, an area of 76 mm^[2] was evaluated in the subpial one. This study was approved by the Committee on Ethics for Scientific Research, Medical University – Varna “Prof. Dr. Paraskev Stoyanov” (protocol no. 20[1]) on April 26, 2012. Results: The tumors included 11 GBMs, 2 gliosarcomas, and 1 WHO Grade II astrocytoma. Only the GBMs were subjected to statistical analysis due to the small sample size. Both the hotspot (P = 0.076) and subpial (P = 0.243) values did not show a correlation with patients' survival, with borderline expression being defined as >3.6% (high) and <3.6% (low). Conclusion: Despite the specific patterns of growth and diffuse spread of CD34+ progenitors, their percentage does not correlate with patients' survival.

Background and Aim: Our previous study demonstrated that SLC22A18 downregulation through promoter methylation and Sequence binding protein 1 (SATB1) upregulation are associated with the development and progression of glioma. This study aimed to examine the effect of combined SLC22A18 and short hairpin RNA (shRNA) targeting SATB1 gene therapy on glioma growth and invasion. Materials and Methods: Here, a combined gene therapy to upregulate SLC22A18 and downregulate SATB1 in malignant glioma was evaluated both in vitro and in vivo. Glioma U251 cells overexpressing SLC22A18 and underexpressing SATB1 were generated to investigate the effects of these changes on cell survival, as measured by the methyl thiazol tetrazolium assay, and on cell invasion, as measured by cell invasion and migration assays. In addition, analysis of the cell cycle was performed using flow cytometry in vitro. The animal experiments were approved by the Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Zhongnan Hospital of Wuhan University Ethics Committees (approval No. ZNHWHU0389, NTPHSHJTUSM046). Results: The upregulation of SLC22A18 and downregulation of SATB1 significantly inhibited growth and invasion in vitro and reduced in vivo tumor growth of human glioma U251 cells. Furthermore, we revealed that U251 cells were arrested at the G0/G1 phase. Similar data for apoptotic glioma cell death were obtained in tumor cells from an in vivo glioma xenograft model after transfection. At the same total dose, the therapeutic effect was markedly better in the glioma xenografts transfected with both SLC22A18 gene and SATB1 short hairpin RNA (shRNA) expression vectors compared with tumors transfected with either agent alone. The levels of SLC22A18 and SATB1 protein expression were respectively increased and decreased in the glioma cells.Conclusion: These results demonstrate that combination treatment with SLC22A18 gene and SATB1 shRNA expression vectors effectively inhibits the growth of human malignant glioma cells both in vitro and in glioma xenografts in vivo, suggesting a promising novel strategy for glioma therapy that warrants further study.

Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and European experts regarding subsequent treatment of Patient 2. Continuation of TMZ and bevacizumab was suggested until further deterioration. Whether tumor-treating field therapy should play a role in this patient could not be evaluated. However, some other molecular targeted agents (e.g. vascular endothelial growth factor receptor tyrosine kinase inhibitors such as regorafenib or apatinib) after bevacizumab failure, the effectiveness of these drugs remains unclear. Conclusion: In clinical practice, although we should follow established guidelines, the final treatment regimen requires informed consent from the patient. Thus, some real-world cases may deviate from the established guidelines. When patients reach end-stage disease with a marked decrease in their performance status and no standard treatment options, active antitumor treatment might be more likely to be attempted in China, while symptomatic treatment is more frequently performed in Europe. Although treatment philosophies for patients with glioma are slightly different between Eastern and Western medical experts, any treatment strategies should satisfy these patients.

Online since 6^th Sep 2017.