Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours.

BACKGROUND: PTEN is a tumour suppressor gene and well-known for being frequently mutated in several cancer types. Loss of immunogenicity can also be attributed to PTEN loss, because of its role in establishing the tumour microenvironment. Therefore, this study aimed to represent the link between PTEN and cGAS-STING activity, a key mediator of inflammation, in tumour samples of glioblastoma patients. METHODS: Tumour samples of 36 glioblastoma patients were collected. After DNA isolation, all coding regions of PTEN were sequenced and analysed. PTEN expression status was also evaluated by qRT-PCR, western blot, and immunohistochemical methods. Interferon-stimulated gene expressions, cGAMP activity, CD8 infiltration, and Granzyme B expression levels were determined especially for the evaluation of cGAS-STING activity and immunogenicity. RESULTS: Mutant PTEN patients had significantly lower PTEN expression, both at mRNA and protein levels. Decreased STING, IRF3, NF-KB1, and RELA mRNA expressions were also found in patients with mutant PTEN. Immunohistochemistry staining of PTEN displayed expressional loss in 38.1% of the patients. Besides, patients with PTEN loss had considerably lower amounts of IFNB and IFIT2 mRNA expressions. Furthermore, CD8 infiltration, cGAMP, and Granzyme B levels were reduced in the PTEN loss group. CONCLUSION: This study reveals the immunosuppressive effects of PTEN loss in glioblastoma tumours via the cGAS-STING pathway. Therefore, determining the PTEN status in tumours is of great importance, like in situations when considering the treatment of glioblastoma patients with immunotherapeutic agents.

The Effect of Preoperative Three Dimensional Modeling and Simulation on Outcome of Intracranial Aneursym Surgery.

OBJECTIVE: Three-dimensional (3D) printing in vascular surgery is trending and is useful for the visualisation of intracranial aneurysms for both surgeons and trainees. The 3D models give the surgeon time to practice before hand and plan the surgery accordingly. The aim of this study was to examine the effect of preoperative planning with 3D printing models of aneurysms in terms of surgical time and patient outcomes. METHODS: Forty patients were prospectively enrolled in this study and divided into two groups : groups I and II. In group I, only the angiograms were studied before surgery. Solid 3D modelling was performed only for group II before the operation and was studied accordingly. All surgeries were performed by the same senior vascular neurosurgeon. Demographic data, surgical data, both preoperative and postoperative modified Rankin scale (mRS) scores, and Glasgow outcome scores (GOS) were evaluated. RESULTS: The average time of surgery was shorter in group II, and the difference was statistically significant between the two groups (p<0.001). However, no major differences were found for the GOS, hospitalisation time, or mRS. CONCLUSION: This study is the first prospective study of the utility of 3D aneurysm models. We show that 3D models are useful in surgery preparation. In the near future, these models will be used widely to educate trainees and pre-plan surgical options for senior surgeons.

Molecular dynamic simulation and functional analysis of pathogenic PTEN mutations in glioblastoma.

PTEN, a dual-phosphatase and scaffold protein, is one of the most commonly mutated tumour suppressor gene across various cancer types in human. The aim of this study therefore was to investigate the stability, structural and functional effects, and pathogenicity of 12 missense PTEN mutations (R15S, E18G, G36R, N49I, Y68H, I101T, C105F, D109N, V133I, C136Y, R173C and N276S) found by next generation sequencing of the PTEN gene in tissue samples obtained from glioblastoma patients. Computational tools and molecular dynamic simulation programs were used to identify the deleterious effects of these mutations. Furthermore, PTEN mRNA and protein expression levels were evaluated by qRT-PCR, Western Blot, and immunohistochemistry staining methods. Various computational tools predicted strong deleterious effects for the G36R, C105F, C136Y and N276S mutations. Molecular dynamic simulation revealed a significant decrease in protein stability for the Y68H and N276S mutations when compared with the wild type protein; whereas, C105F, D109N, V133I and R173C showed partial stability reduction. Significant residual fluctuations were observed in the R15S, N49I and C136Y mutations and radius of gyration graphs revealed the most compact structure for D109N and least for C136Y. In summary, our study is the first one to show the presence of PTEN E18G, N49I, D109N and N276S mutations in glioblastoma patients; where, D109N is neutral and N276S is a damaging and disease-associated mutation.Communicated by Ramaswamy H. Sarma.

Complications of adult spinal deformity surgery: A literature review.

Purpose: Adult spinal deformity incidence increases accordingly as the population ages. Even though surgery is the best option for the treatment, the complications due to surgery are pretty challenging. This study aims to review the complication rates of adult spinal deformity surgery. Methods: A literature review of the last decade was performed searching for the query "Adult spine deformity and complication." This search yielded 2781 results, where 79 articles were chosen to investigate the complications of adult spinal deformity surgery. In addition, the demographic data, surgical interventions, and complications were extracted from the publications. Results: A total of 26,207 patients were analyzed, and 9138 complications were found (34.5%). Implant failure, including screw loosening, breakage, distal and proximal junctional kyphosis, were the most common complications. The neurologic complications were about 10.8%, and the infection rate was 3.6%. Cardiac and pulmonary complications were about 4.8%. Discussion: Age, body mass index, smoking, osteoporosis, and other comorbidities are the significant risk factors affecting adult spinal deformity surgery. Presurgical planning and preoperative risk factor assessment must be done to avoid complications. Furthermore, intra and postoperative complications affect the patients' quality of life and length of stay, and hospital readmissions. Revision surgery also increases the risk of complications. Conclusion: Good patient evaluation before surgery and careful planning of the surgery are essential in avoiding complications of adult spinal deformity.

Complications of occipitocervical fixation: retrospective review of 128 patients with 5-year mean follow-up.

PURPOSE: Occipitocervical fusion is necessary for many pathologies of the craniocervical junction. The anatomy of the region is unique, and fusion can cause significant morbidity. This retrospective review aims to investigate the complication rates and outcomes of occipitocervical fixation. MATERIAL AND METHODS: This is a retrospective review of 128 patients with occipitocervical fixation operated between 1994 and 2020. The average follow-up is 63 months. RESULTS: The indications of occipitocervical fixation were basilar invagination (53 patients; 41.4%), trauma (25 patients; 19.5%), tumor (23 patients; 18%), instability due to rheumatoid arthritis (13 patients; 10.2%), cervical deformity (7 patients; 5.5%) and os odontoideum (7 patients; 5.5%). There were six early postoperative (1st month) deaths. We observed complications in 67 patients (52%). Most common complication was implant-related (32%), followed by wound problems (23.4%), systemic and other complications (11.7%), neurologic complications (6.2%). Implants are removed in 31 patients (24%) for different reasons: deep wound infection (7), local pain and restriction of head movements (21), respiratory distress and swallowing problems (2), screw fracture and local pain (1). CONCLUSIONS: Occipitocervical fixation has quite large number of complications and significantly restricts head movements. With the advent of our biomechanical concepts, indications should be limited, and shorter cervical fixations should be preferred. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Giant sacral schwannomas.

Sacral schwannomas are very rare tumors. There are merely around 50 cases reported in the literature most of which are case presentations. In this study we present a 13-case series, which is one of the most extensive series in the literature. Thirteen giant sacral schwannoma cases operated at Ege University, Faculty of Medicine, Neurosurgery Department between 1995 and 2010 are investigated retrospectively. All patients were assessed with direct radiography, computerized tomography (CT) and magnetic resonance imaging (MRI). The patients were operated, after the diagnosis through biopsy patients with Sridhar Type V classification are included in the study. Five patients were male, eight were female and the average age was 37.1 (ranging between 14 and 55). All the patients were suffering from back and leg pain at the time of consultation. Four patients had sphincter problems and three had weakness in the leg. After the biopsy and histological analysis, intralesionary resections were performed. Five patients went through both anterior and posterior interventions, six patients had only posterior and two had just anterior intervention. One patient had iliac vein injury during the anterior surgery. This patient was reoperated for embolectomy and vein graft because of thrombosis. Average follow-up period was 8.1 years (1-15 years). All patients were assessed with MR annually. A small residual tumor was detected in two patients, however they were not reoperated. Although sacral schwannomas are rare tumors, the diagnosis is not so difficult with CT and MRI. In this study, we suggest biopsy for predetermination of the nature of the tumor as it affects the treatment choice and the method of operation. Surgically, a simple intralesionary excision is an appropriate choice.

Fenestration methods for Sylvian arachnoid cysts--endoscopy or microsurgery.

INTRODUCTION: Two different approaches to fenestration, endoscopic and microsurgical, are in use for Sylvian arachnoid cysts (SACs), the most frequent among intracranial arachnoid cysts. We presented the clinical data and compared our results, with regard to technique and clinical success, with either microsurgical or neuroendoscopic fenestration of SACs. MATERIALS AND METHODS: Twenty-nine patients who subjected to cysto-cisternostomy by the same team, using either of the two methods, were studied retrospectively. RESULTS: Thirteen patients underwent microsurgery, and 16 had endoscopic cysto-cisternostomy. No reoperation was needed in either of these groups, i.e., full clinical and radiological success was achieved in both. The complication rate was 23% in the microsurgery patients and 47% in the endoscopic surgery group, with no statistically significant difference. CONCLUSIONS: No relevant differences between the two methods are seen either in the published data or in our results. Adding our results to the published data, both techniques were reviewed in a discussion of the one that allows a better controlled or safer fenestration. We conclude that endoscopic fenestration of SACs is not superior to microsurgical cyst fenestration, and the latter seems safer.