Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.

Zinc fingers and homeoboxes 1 (ZHX1) is a transcription repressor that has been implicated in the tumorigenesis and progression of diverse tumors. The functional role and regulating mechanism of ZHX1 has not been elucidated in glioblastoma (GBM). Previous reports have suggested that a large number of non-coding RNAs play a vital role in glioma initiation and progression. This study aimed to investigate the functional role and co-regulatory mechanisms of the metastasis-associated lung adenocarcinoma transcript-1 (MALAT1)/ microRNA-199a (miR-199a)/ZHX1 axis in GBM. We analyzed the expression of the MALAT1/miR-199a/ZHX1 axis and its correlation with patients’ overall survival using two different glioma gene-expression datasets. A series of in vitro and in vivo studies including dual luciferase reporter assay, fluorescence in situ hybridization (FISH), RNA immunoprecipitation, and pull-down experiments were completed to elucidate the biological significance of the MALAT1/miR-199a/ZHX1 axis in promoting glioma proliferation and progression. Elevated ZHX1 expression correlated with poor prognosis in GBM patients, and in vitro studies demonstrated that ZHX1 attenuated GBM cell apoptosis by downregulation of pro-apoptotic protein (Bax) and upregulation of anti-apoptotic protein (Bcl-2). Furthermore, knockdown of MALAT1 inhibited GBM proliferation and progression in vitro and reduced tumor volume and prolonged survival in an orthotopic GBM murine model. Finally, we demonstrated that MALAT1 promoted ZHX1 expression via acting as a competing endogenous RNA by sponging miR-199a. The MALAT1/miR-199a/ZHX1 axis promotes GBM cell proliferation and progression in vitro and in vivo, and its expression negatively correlates with GBM patient survival. Blocking the MALAT1/miR-199a/ZHX1 axis can serve as a novel therapeutic strategy for treating GBM.

BackgroundNoninvasive intraoperative optical biopsy that provides real-time imaging of histoarchitectural (cell resolution) features of brain tumors, especially at the margin of invasive tumors, would be of great value. To assess clinical-grade confocal laser endomicroscopy (CLE) and to prepare for its use intraoperatively in vivo, we performed an assessment of CLE ex vivo imaging in brain lesions.MethodsTissue samples from patients who underwent intracranial surgeries with fluorescein sodium (FNa)–based wide-field fluorescence guidance were acquired for immediate intraoperative ex vivo optical biopsies with CLE. Hematoxylin-eosin–stained frozen section analysis of the same specimens served as the gold standard for blinded neuropathology comparison. FNa 2 to 5 mg/kg was administered upon induction of anesthesia, and FNa 5 mg/kg was injected for CLE contrast improvement. Histologic features were identified, and the diagnostic accuracy of CLE was assessed.ResultsOf 77 eligible patients, 47 patients with 122 biopsies were enrolled, including 32 patients with gliomas and 15 patients with other intracranial lesions. The positive predictive value of CLE optical biopsies was 97% for all specimens and 98% for gliomas. The specificity of CLE was 90% for all specimens and 94% for gliomas. The second FNa injection in seven patients, a mean of 2.6 h after the first injection, improved image quality and increased the percentage of accurately diagnosed images from 67% to 93%. Diagnostic CLE features of lesional glioma biopsies and normal brain were identified. Seventeen histologic features were identified.ConclusionsResults demonstrated high specificity and positive predictive value of ex vivo intraoperative CLE optical biopsies and justify an in vivo intraoperative trial. This new portable, noninvasive intraoperative imaging technique provides diagnostic features to discriminate lesional tissue with high specificity and is feasible for incorporation into the fluorescence-guided surgery workflow, particularly for patients with invasive brain tumors.

PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

Background: High-grade glioma (HGG) is associated with a dismal prognosis despite significant advances in adjuvant therapies, including chemotherapy, immunotherapy, and radiotherapy. Extent of resection continues to be the most important independent prognosticator of survival. This underlines the significance of increasing gross total resection (GTR) rates by using adjunctive intraoperative modalities to maximize resection with minimal neurological morbidity. 5-aminolevulinic acid (5-ALA) is the only US Food and Drug Administration–approved intraoperative optical agent used for fluorescence-guided surgical resection of gliomas. Despite several studies on the impact of intra-operative 5-ALA use on the extent of HGG resection, a clear picture of how such usage affects patient survival is still unavailable. Methods: A systematic review was conducted of all relevant studies assessing the GTR rate and survival outcomes [overall survival (OS) and progression-free survival (PFS)] in HGG. A meta-analysis of eligible studies was performed to assess the influence of 5-ALA-guided resection on improving GTR, OS, and PFS. GTR was defined as >95% resection. Results: Of 23 eligible studies, 19 reporting GTR rates were included in the meta-analysis. The pooled cohort had 998 patients with HGG, including 796 with newly diagnosed cases. The pooled GTR rate among patients with 5-ALA–guided resection was 76.8% (95% confidence interval, 69.1–82.9%). A comparative subgroup analysis of 5-ALA–guided vs. conventional surgery (controlling for within-study covariates) showed a 26% higher GTR rate in the 5-ALA subgroup (odds ratio, 3.8; P < 0.001). There were 11 studies eligible for survival outcome analysis, 4 of which reported PFS. The pooled mean difference in OS and PFS was 3 and 1 months, respectively, favoring 5-ALA vs. control ( P < 0.001). Conclusions: This meta-analysis shows a significant increase in GTR rate with 5-ALA–guided surgical resection, with a higher weighted GTR rate (~76%) than the pivotal phase III study (~65%). Pooled analysis showed a small yet significant increase in survival measures associated with the use of 5-ALA. Despite the statistically significant results, the low level of evidence and heterogeneity across these studies make it difficult to conclusively report an independent association between 5-ALA use and survival outcomes in HGG. Additional randomized control studies are required to delineate the role of 5-ALA in survival outcomes in HGG.

OBJECTIVEMeningiomas at the falcotentorial junction represent a rare subgroup of complex meningiomas. Debate remains regarding the appropriate treatment strategy for and optimal surgical approach to these tumors, and surgical outcomes have not been well described in the literature. The authors reviewed their single-institution experience in the management, approach selection, and outcomes for patients with falcotentorial meningiomas.METHODSFrom the medical records, the authors identified all patients with falcotentorial meningiomas treated with resection at the Barrow Neurological Institute between January 2007 and October 2017. Perioperative clinical, surgical, and radiographic data were retrospectively collected. For patients who underwent the supracerebellar infratentorial approach, the tentorial angle was defined as the angle between the line joining the nasion with the tuberculum sellae and the tentorium in the midsagittal plane.RESULTSFalcotentorial meningiomas occurred in 0.97% (14/1441) of the patients with meningiomas. Most of the patients (13/14) were female, and the mean patient age was 59.8 ± 11.3 years. Of 17 total surgeries (20 procedures), 11 were single-stage primary surgeries, 3 were two-stage primary surgeries (6 procedures), 2 were reoperations for recurrence, and 1 was a reoperation after surgery had been aborted because of brain edema. Hydrocephalus was present in 5 of 17 cases, 4 of which required additional treatment. Various approaches were used, including the supracerebellar infratentorial (4/17), occipital transtentorial/transfalcine (4/17), anterior interhemispheric transsplenial (3/17), parietal transventricular (1/17), torcular (2/17), and staged supracerebellar infratentorial and occipital transtentorial/transfalcine (3/17) approaches. Of the 17 surgeries, 9 resulted in Simpson grade IV resection, and 3, 1, and 4 surgeries resulted in Simpson grades III, II, and I resection, respectively. The tentorial angle in cases with Simpson grade I resection was significantly smaller than in those with an unfavorable resection grade (43.3° ± 4.67° vs 54.0° ± 3.67°, p = 0.04). Complications occurred in 10 of 22 approaches (17 surgeries) and included visual field defects (6 cases, 2 permanent and 4 transient), hemiparesis (2 cases), hemidysesthesia (1 case), and cerebellar hematoma (1 case).CONCLUSIONSFalcotentorial meningiomas are challenging lesions. A steep tentorial angle is an unfavorable preoperative radiographic factor for achieving maximal resection with the supracerebellar infratentorial approach. Collectively, the study findings show that versatility is required to treat patients with falcotentorial meningiomas and that treatment goals and surgical approach must be individualized to obtain optimal surgical results.

OBJECTIVEThe ventral jugular foramen and the infrapetrous region are difficult to access through conventional lateral and posterolateral approaches. Endoscopic endonasal approaches to this region are obstructed by the eustachian tube (ET). This study presents a novel strategy for mobilizing the ET while preserving its integrity. Qualitative and quantitative comparisons with previous ET management paradigms are also presented.METHODSTen dry skulls were analyzed. Four ET management strategies were sequentially performed on a total of 6 sides of cadaveric head specimens. Four measurement groups were generated: in group A, the ET was intact and not mobilized; in group B, the ET was mobilized inferolaterally; in group C, the ET underwent anterolateral mobilization; and in group D, the ET was resected. ET range of mobilization, surgical exposure area, and surgical freedom were measured and compared among the groups.RESULTSWide exposure of the infrapetrous region and jugular foramen was achieved by removing the pterygoid process, unroofing the cartilaginous ET up to the level of the posterior aspect of the foramen ovale, and detaching the ET from the skull base and soft palate. Anterolateral mobilization of the ET facilitated significantly more retraction (a 126% increase) of the ET than inferolateral mobilization (mean ± SD: 20.8 ± 11.2 mm vs 9.2 ± 3.6 mm [p = 0.02]). Compared with group A, groups C and D had enhanced surgical exposure (142.5% [1176.9 ± 935.7 mm2] and 155.9% [1242.0 ± 1096.2 mm2], respectively, vs 485.4 ± 377.6 mm2 for group A [both p = 0.02]). Furthermore, group C had a significantly larger surgical exposure area than group B (p = 0.02). No statistically significant difference was found between the area of exposure obtained by ET removal and anterolateral mobilization. Anterolateral mobilization of the ET resulted in a 39.5% increase in surgical freedom toward the exocranial jugular foramen compared with that obtained through inferolateral mobilization of the ET (67.2° ± 20.5° vs 48.1° ± 6.7° [p = 0.047]) and a 65.4% increase compared with that afforded by an intact ET position (67.2° ± 20.5° vs 40.6° ± 14.3° [p = 0.03]).CONCLUSIONSAnterolateral mobilization of the ET provides excellent access to the ventral jugular foramen and infrapetrous region. The surgical exposure obtained is superior to that achieved with other ET management strategies and is comparable to that obtained by ET resection.

BackgroundWe assessed a new robotic visualization platform with novel user-control features and compared its performance to the previous model of operative microscope.MethodsIn a neurosurgery research laboratory, we performed anatomical dissections and assessed robotic, exoscopic, endoscopic, fluorescence functionality. Usability and functionality were tested in the operating room over 1 year.ResultsThe robotic microscope showed higher sensitivity for fluorescein sodium, higher detail in non-fluorescent background, and recorded/presented pictures with color quality similar to observation through the oculars. PpIX visualization was comparable to the previous microscope. Near-infrared indocyanine green imaging 3-step replay allowed for more convenient accurate assessment of blood flow. Point lock and pivot point functions were used in dissections to create 3D virtual reality microsurgical anatomy demonstrations. Pivot point control was particularly useful in deep surgical corridors with dynamic retraction. 3D exoscopic function was successfully used in brain tumor and spine cases. Endoscopic assistance was used for around-the-corner views in minimally invasive approaches. We present illustrative cases highlighting utility and new ways to control the operative microscope.ConclusionImprovements of the robotic visualization platform include intraoperative fluorescence visualization using FNa, integrated micro-inspection tool, improved ocular imaging clarity, and exoscopic mode. New robotic movements positively assist the surgeon and provide improved ergonomics and a greater level of intraoperative comfort, with the potential to increase the viewing quality. New operational modes also allow significant impact for anatomy instruction. With the increasing number and complexity of functions, surgeons should receive additional training in order to avail themselves of the advantages of the numerous novel features.