Applying the en-bloc technique in corpus callosum glioblastoma surgery contributes to maximal resection and better prognosis: a retrospective study.

BACKGROUND: Corpus callosum glioblastoma (ccGBM) is a specific type of GBM and has worse outcomes than other non-ccGBMs. We sought to identify whether en-bloc resection of ccGBMs based on T2-FLAIR imaging contributes to clinical outcomes and can achieve a satisfactory balance between maximal resection and preservation of neurological function. METHODS: A total of 106 adult ccGBM patients (including astrocytoma, WHO grade 4, IDH mutation, and glioblastoma) were obtained from the Department of Neurosurgery in Nanfang Hospital between January 2008 and December 2018. The clinical data, including gender, age, symptoms, location of tumor, involvement of eloquent areas, extent of resection (EOR), pre- and postoperative Karnofsky Performance Status (KPS) scales, and National Institute of Health stroke scale (NIHSS) scores were collected. Propensity score matching (PSM) analysis was applied to control the confounders for analyzing the relationship between the en-bloc technique and EOR, and the change in the postoperative KPS scales and NIHSS scores. RESULTS: Applying the en-bloc technique did not negatively affect the postoperative KPS scales compared to no-en-bloc resection (P = 0.851 for PSM analysis) but had a positive effect on preserving or improving the postoperative NIHSS scores (P = 0.004 for PSM analysis). A positive correlation between EOR and the en-bloc technique was identified (r = 0.483, P < 0.001; r = 0.720, P < 0.001 for PSM analysis), indicating that applying the en-bloc technique could contribute to enlarged maximal resection. Further survival analysis confirmed that applying the en-bloc technique and achieving supramaximal resection could significantly prolong OS and PFS, and multivariate analysis suggested that tumor location, pathology, EOR and the en-bloc technique could be regarded as independent prognostic indicators for OS in patients with ccGBMs, and pathology, EOR and the en-bloc technique were independently correlated with patient's PFS. Interestingly, the en-bloc technique also provided a marked reduction in the risk of tumor recurrence compared with the no-en-bloc technique in tumors undergoing TR, indicating that the essential role of the en-bloc technique in ccGBM surgery (HR: 0.712; 95% CI: 0.535-0.947; P = 0.02). CONCLUSIONS: The en-bloc technique could contribute to achieving an enlarged maximal resection and could significantly prolong overall survival and progression-free survival in patients with ccGBMs.

Supramaximal resection based on en-bloc technique reduces tumor burden and prolongs survival in primary supratentorial lobar glioblastoma.

PURPOSE: Resection beyond the contrast-enhanced zone contributed to reduce tumor burden and prolong survival in glioblastomas. The optimal extent of resection (EOR) and how to achieve it are worthy of continuous investigation for obtaining a satisfactory balance between maximal resection and the preservation of neurological function. METHODS: A total of 340 adult supratentorial lobar glioblastomas (included astrocytoma, WHO 4, IDH mutation and glioblastoma) were retrospectively evaluated. The clinical data, EOR, technique of resection, postoperative complications, overall survival (OS) and progression-free survival (PFS) were assessed by univariate, multivariate and propensity score matched analysis. Histological staining was performed to comprehend the effect of the membranous structures and the cell distribution in tumoral and peritumoral regions. RESULTS: Supramaximal resection (SMR) was confirmed as resection with 100% EORCE and > 50% EORnCE in glioblastomas by Cox proportional hazards model. Histological results showed SMR reduced the cell density of surgical edge compared to total resection. En-bloc technique based on membranous structures, which had blocking effect on tumoral invasion, contributed to achieve SMR. Moreover, applying en-bloc technique and achieving SMR did not additionally deteriorate neurological function and had similarly effects on the improvement of neurological function. Multivariate analysis confirmed that IDH1 status, technique of resection and EOR were independently correlated with PFS, and > 64 years old, IDH1 status, technique of resection, EOR and preoperative NIHSS were independently correlated with OS. CONCLUSIONS: Applying en-bloc technique and achieving SMR, which could reduce tumor burden and did not increase additional complications, both had remarkedly positive effects on clinical outcomes in patients with primary supratentorial lobar glioblastomas.

Classification of unilateral thalamic gliomas predicts tumor resection and patient's survival: a single center retrospective study.

BACKGROUND: To propose our classification about unilateral thalamic gliomas, and to describe relationship between the classification and clinical characteristics including symptoms, surgical approaches and survival, which should contribute to the treatment and the prognostic prediction of unilateral thalamic gliomas. METHODS: A total of 66 adult unilateral thalamic glioma patients with pathologic confirmation between January 2010 and December 2018 were retrospectively investigated. RESULTS: Unilateral thalamic gliomas could be divided into quadrigeminal cistern and ventricle extension type (Type Q), lateral type (Type L) and anterior type (Type A) according to tumor location, extensive polarity and location of ipsilateral posterior limb of internal capsule. Each subtype of QLA classification could match with one kind of corresponding approach. Preoperative symptoms including headache, dyskinesia, aphasia, hydrocephalus and KPS scores, and pathological features including H3K27M mutation and P53 expression were correlated with QLA classification. Further analysis confirmed that Type Q tumors had a higher rate of total resection and a significantly longer survival time compared to Type L and Type A tumors, with similar improved and deteriorated rates of symptoms. Univariate and multivariate analysis demonstrated QLA classification was remarkedly associated with overall survival and could be considered as an independent prognostic factor in patients with unilateral thalamic gliomas. CONCLUSIONS: Unilateral thalamic glioma could be divided into 3 subtypes by imaging characteristics, symptoms and survival. QLA classification could predict tumor resection and the prognosis and could contribute to the planning of therapeutic strategy in patients with unilateral thalamic gliomas.

Ventricle wall resection contributes to supramaximal resection and prognosis in SVZ-involved frontal gliomas: A single center retrospective study.

BACKGROUND: Frontal glioma frequently invaded the subventricular zone (SVZ), which existed glioma stem cells and might be involved in the development of primary and recurrent gliomas. We attempted to identify whether ventricle wall resection contributed to the maximal extent of resection (EOR) and increased the patient's survival during frontal glioma resection. METHODS: A total of 151 adult patients with primary SVZ-involved frontal gliomas were obtained between January 2012 and December 2018. We analyzed clinical data, EOR, complications and survival profiles between the ventricle wall group and the ventricle intact/opening group. RESULTS: Applying ventricle wall removal had similar effect on the improvement of neurological function compared to applying ventricle intact/opening and did not increase the incidence of new neurological deficits, hydrocephalus, and ependymal dissemination in SVZ-involved frontal gliomas. A positive correlation was identified between EOR and the ventricle wall handling (r = 0.487, P < 0.001), which indicated that ventricle wall resection could contribute to achieve supramaximal resection. Applying supramaximal resection and ventricle wall resection could significantly prolong overall survival and progression free survival. Ventricle wall resection could be regarded as an independent prognostic indicator for both overall survival and progression free survival in patients with SVZ-involved frontal gliomas. CONCLUSIONS: Ventricle wall resection in SVZ-involved frontal gliomas could contribute to achieve supramaximal resection and could significantly prolong overall survival and progression free survival.

HMGA1 stimulates MYH9-dependent ubiquitination of GSK-3ß via PI3K/Akt/c-Jun signaling to promote malignant progression and chemoresistance in gliomas.

Myosin heavy chain 9 (MYH9) plays an essential role in human diseases, including multiple cancers; however, little is known about its role in gliomas. In the present study, we revealed that HMGA1 and MYH9 were upregulated in gliomas and their expression correlated with WHO grade, and HMGA1 promoted the acquisition of malignant phenotypes and chemoresistance of glioma cells by regulating the expression of MYH9 through c-Jun-mediated transcription. Moreover, MYH9 interacted with GSK-3ß to inhibit the expression of GSK-3ß protein by promoting its ubiquitination; the downregulation of GSK-3ß subsequently promoted the nuclear translocation of ß-catenin, enhancing growth, invasion, migration, and temozolomide resistance in glioma cells. Expression levels of HMGA1 and MYH9 were significantly correlated with patient survival and should be considered as independent prognostic factors. Our findings provide new insights into the role of HMGA1 and MYH9 in gliomagenesis and suggest the potential application of HMGA1 and MYH9 in cancer therapy in the future.

Multifunctional superparamagnetic nanoparticles conjugated with fluorescein-labeled designed ankyrin repeat protein as an efficient HER2-targeted probe in breast cancer.

Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein (DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging. Our results showed that SPIO-G3-5MF nanoparticles, which possessed uniform size of about 100 nm, favorable dispersity and low cytotoxicity, could selectively bind to HER2-positive breast cancer cells even in the presence of trastuzumab. Biodistribution assay demonstrated that abundant accumulation and long retention of SPIO-G3-5MF were observed in HER2-positive transplantation breast tumors although a portion of SPIO-G3-5MF nanoparticles were unavoidably captured by liver and spleen. Further MR imaging revealed that SPIO-G3-5MF could selectively image HER2-positive transplantation breast tumors, yielding remarkable T2 signal reduction (50.33 ± 2.90% at 6 h and 47.29 ± 9.36% at 24 h). Our study suggested that SPIO-G3-5MF might be a promising MR molecular probe for diagnosing and monitoring HER2 expression state of breast cancer in the future.