Perioperative Means to Prevent Surgical Site Infections following Elective Craniotomies: A Single-Center Experience.

Background Postoperative surgical site infections are a recognized complication following craniotomies with an associated increase in morbidity and mortality. Several studies have attempted to identify bundles of care to reduce the incidence of infections. Our study aims to clarify which perioperative measures play a role in reducing surgical infection rates further. Methods This study is a retrospective audit of all elective craniotomies in years 2018 to 2019. The primary endpoint was the surgical site infection rate at 30 days and 4 months after the procedure. Univariate analysis was used to identify factors predictive of postoperative infection. Results 344 patients were included in this study. Postoperative infections were observed in 5.2% of our cohort. No postoperative infections occurred within 4 months in patients receiving perioperative hair wash and intrawound vancomycin powder. In univariate analysis, craniotomy size (Fisher's exact test, p = 0.05), lack of perioperative hair wash, and vancomycin powder use (Fisher's exact test, p = 0.01) were predictive of postoperative infection. No complications relative to the use of intrawound vancomycin were observed. Conclusion Our study demonstrates that simple measures such as perioperative hair wash combined with intrawound vancomycin powder in addition to standard practice can help reducing infection rates with negligible risks and acceptable costs. Our results should be validated further in future prospective studies.

Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial.

Background: Glioblastoma is a high-grade aggressive neoplasm whose outcomes have not changed in decades. In the current treatment pathway, tumour growth continues and remains untreated for several weeks post-diagnosis. Intensified upfront therapy could target otherwise untreated tumour cells and improve the treatment outcome. POBIG will evaluate the safety and feasibility of single-fraction preoperative radiotherapy for newly diagnosed glioblastoma, assessed by the maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV). Methods: POBIG is an open-label, dual-centre phase I dose and volume escalation trial that has received ethical approval. Patients with a new radiological diagnosis of glioblastoma will be screened for eligibility. This is deemed sufficient due to the high accuracy of imaging and to avoid treatment delay. Eligible patients will receive a single fraction of preoperative radiotherapy ranging from 6 to 14 Gy followed by their standard of care treatment comprising maximal safe resection and postoperative chemoradiotherapy (60 Gy/30 fr) with concurrent and adjuvant temozolomide). Preoperative radiotherapy will be directed to the part of the tumour that is highest risk for remaining as postoperative residual disease (hot spot). Part of the tumour will remain unirradiated (cold spot) and sampled separately for diagnostic purposes. Dose/volume escalation will be guided by a Continual Reassessment Method (CRM) model. Translational opportunities will be afforded through comparison of irradiated and unirradiated primary glioblastoma tissue. Discussion: POBIG will help establish the role of radiotherapy in preoperative modalities for glioblastoma. Trial registration: NCT03582514 (clinicaltrials.gov).

Rapid early progression (REP) of glioblastoma is an independent negative prognostic factor: Results from a systematic review and meta-analysis.

Background: In patients with newly diagnosed glioblastoma, rapid early progression (REP) refers to tumor regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis appraised previously published data on REP to better characterize and understand it. Methods: Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to October 21, 2021. Studies describing the incidence of REP-tumor growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly diagnosed glioblastoma were included. The primary outcome was REP incidence. Results: From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0-58.8 y). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1-1.5). The median number of days between MRI scans was 34 days (IQR 18-45 days). The mean incidence rate of REP was 45.9% (range 19.3%-72.0%) and significantly lower in studies employing functional imaging to define REP (P < .001). REP/non-REP groups were comparable with respect to age (P = .99), gender (P = .33) and time between scans (P = .81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30-2.43, P < .001), shortened progression-free survival (HR 1.78, 95% CI 1.30-2.43, P < .001), subtotal resection (OR 6.96, 95% CI 4.51-10.73, P < .001) and IDH wild-type versus mutant tumors (OR 0.20, 95% CI 0.02-0.38, P = .03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72-2.28, P = .39). Conclusions: REP occurs in almost half of patients with newly diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.

Safety and feasibility of posterior fossa neurosurgery in the supine position - A UK series from a large centre.

BACKGROUND: Posterior fossa surgery in the supine position remains a relatively underutilised approach, compared to the routinely performed prone, park-bench or sitting positions. This surgical approach may confer additional advantages over other modalities commonly restricted by patient co-morbidity and anaesthetic concerns. The purpose of this article is to highlight this approach as a potential viable, safe and alternative approach. METHODS: We retrospectively collected data of all supine infra-tentorial/posterior fossa surgery by one surgeon between 2015 and the present via our electronic patient record system. Demographic data alongside duration of surgery, ASA grading, location of lesions, length of stay, presence of post-operative infections, presence of post-operative CSF leak/pseudomeningocele and post-operative mortality were assessed. RESULTS: A total of 64 procedures on 58 patients were identified. Of the procedures, 60 were performed for neoplasms (93.8%). Mean overall surgical time was 176 min. Median ASA grade for tumour surgery was 3. Median length of stay was 3 days. Of the non-emergency tumour cases (n = 53), 43 (81.1%) lesions were located in the cerebellar hemisphere, the remainder were in the vermis and tentorium. There were 6 documented post-operative infections (9.4%). The rates of CSF-related complications were: CSF Leak 1.6% (1/64) and Pseudomeningocele 1.6% (1/64). 30-day mortality was 1.6% (1/64). CONCLUSION: This study suggests that supine positioning is a safe alternative to be considered when operating upon posterior fossa lesions. Further studies are warranted to assess efficacy of this approach, but it can be considered for wider use in the UK and further afield.

Does the Use of Surgical Adjuncts Affect Postoperative Infection Rates in Neuro-oncology Surgery?

BACKGROUND: Surgical site infection (SSI) is a significant cause of postoperative morbidity and mortality. As oncologic care advances, the use of surgical adjuncts such as intraoperative ultrasound (US), 5-aminolevulinic acid (5-ALA), and neurophysiologic monitoring has increased. This study set out to identify whether the use of surgical adjuncts in supratentorial tumor surgery lead to increased operative time or increased rates of SSI. METHODS: This is a retrospective study at a large tertiary clinical neurosciences center in the UK. We included all patients who underwent an elective supratentorial craniotomy for a tumor over a 12 month period. We retrospectively assessed whether patients had had a postoperative infection at 30 days or 4 months using our electronic patient record system. RESULTS: A total of 267 patients were included. The median age was 58 years (range: 17-87 years) with roughly equal numbers of men and women (men: 138 of 267, 52%). Most operations were carried out for gliomas (149 of 267, 56%) or metastases (61 of 267, 23%). The median length of surgery was 3 hours 6 minutes, with 24% lasting >4 hours. The overall infection rate was 4.5%. Intraoperative monitoring and 5-ALA was associated with longer operative times although not necessarily larger craniotomy sizes, whereas intraoperative US was associated with a shorter operative time and smaller craniotomy size. These adjuncts were not associated with an increased risk of infection. CONCLUSIONS: This study adds reassurance that although some surgical adjuncts lead to increased operative times, in our study there was no apparent increased risk of infection as a result of this.

Minimally Invasive Resection of Brain Metastases.

BACKGROUND: Minimally invasive resection of brain metastases aims to maximize resection while minimizing brain trauma. METHODS: Patients with 1 or more metastases that underwent resection following neuro-oncology multidisciplinary meeting discussion from September 2014 to October 2018, with pre- and postoperative magnetic resonance imaging, were included. All patients including posterior fossa metastases or multiple metastases were positioned supine. Hair was not shaved. Volumetric postcontrast T1 magnetic resonance imaging was used for incision planning and neuronavigation. The craniotomy site was tailored to tumor depth according to keyhole principles and ranged between 2 and 5 cm. Intraoperative monitoring and awake mapping were carried out in selected cases. RESULTS: Out of 320 consecutive patients with brain metastases, 44 patients were identified as suitable for minimally invasive resection. Nine patients had no postoperative imaging and were excluded. There were 38 metastases in 35 patients. There were 18 cerebellar metastases, 10 frontal, 3 parietal, 3 occipital, 2 temporal, 1 intraventricular, and 1 basal ganglia. Median length of stay was 3 days (range, 1-24). Average tumor volume was 54.7 cm3 (range, 10-240 cm3). Endoscopic assistance was used in 4 patients. Median performance status improved from 2 to 1 (range, preoperative: 0-4; postoperative: 0-2). Median survival was 14.7 months. CONCLUSIONS: Minimally invasive resection of brain metastasis is safe and effective, and in selected cases confers advantages compared with standard techniques.

Intracranial aneurysms in patients with internal carotid artery occlusion: management and outcome in 22 cases.

BACKGROUND: There is little information about clinical characteristics, management, and outcome of patients with intracranial aneurysms and internal carotid artery occlusion. We will describe clinical characteristics, treatment and outcome of patients with coexistent internal carotid artery occlusion and intracranial aneurysms. METHODS: We conducted a retrospective chart review of 22 patients (eight males and 14 females) with coexistent internal carotid artery (ICA) occlusion and intracranial aneurysms. RESULTS: This series includes 14 females and eight males with a mean age of 63 years (range, 49 to 80). These patients harbored a total of 35 aneurysms, which were located on the same side of the ICA occlusion in five cases, on the contralateral side in 20 cases, while in ten cases the aneurysm had a midline location (AcomA 9, Basilar tip 1). Treatment consisted of surgery for eight aneurysms and endovascular embolization for 13 aneurysms. No invasive treatment was recommended for 14 aneurysms (eight patients with single aneurysm). No permanent perioperative or periprocedural complications occurred in the selected group of patients undergoing invasive treatment. At a mean follow-up of 57 months (range, 3-203), no patient had a subarachnoid hemorrhage and three patients had died of causes not related to the aneurysm. CONCLUSION: Surgical and endovascular treatment can be accomplished safely in selected patients with coexistent ICA occlusion and intracranial aneurysms. Conservative treatment is a valid alternative, especially in elderly patients or in patients with very small aneurysms, especially if not located along the collateral pathway.

Potential of anti-cancer therapy based on anti-miR-155 oligonucleotides in glioma and brain tumours.

MicroRNAs are aberrantly expressed in many cancers and can exert tumour-suppressive or oncogenic functions. As oncomirs promote growth of cancer cells and support survival during chemotherapy, thus microRNA-silencing therapies could be a valuable approach to be associated with anticancer drugs and chemotherapy treatments. miR-155 microRNA was found overexpressed in different types of cancer, such as leukaemias (PML, B-cell lymphomas), lung cancer and glioblastoma. GABA-A receptor downregulation was found correlated with glioma grading, with decreasing levels associated with higher grade of malignancies. A relationship between knock-down of miR-155 and re-expression of GABRA 1 protein in vivo was recently individuated. This finding has implication on the effectiveness of RNA-silencing approaches against miR-155 with the scope to control proliferation and signalling pathways regulated by GABA-A receptor. Applying microRNAs for treatment of brain tumours poses several problems, and fields to be solved are mainly the passage of the brain-blood barrier and the targeted delivery to specific cell types. Glioblastoma multiforme cells bud off microvesicles that deliver cytoplasmic contents to nearby cells. Thus, the exploitation of these mechanisms to deliver antagomir therapeutics targeting microvescicles in the brain could take the lead in the near future in the treatment for brain cancers in substitution of invasive surgical intervention.

Extended endoscopic transplanum-transtuberculum approach for pituitary adenomas.

Few pituitary adenomas require removal through a transcranial route. This may be associated with more significant morbidity and mortality, compared to the transsphenoidal approach. An endoscopic, extended, transplanum-transtuberculum approach (ETTA) in selected pituitary adenomas may offer an alternative to the transcranial route. We describe our technique and experience of ETTA in pituitary adenomas over 10 years. Between 2000 and 2010, we performed 700 endoscopic endonasal procedures for pituitary adenomas. Nineteen patients (13 men; mean age, 48 years; range, 22-76 years) underwent 22 ETTAs. Thirteen patients had non-functioning adenomas. Three tumor groups were identified: (1) tumors developing in or around the pituitary stalk; (2) tumours with sub- frontal extension and (3) tumours with a major extrasellar component. Mean follow-up was 37 months (range 6-72 months). Gross total resection was achieved in 11 procedures (no recurrences), with partial tumour resection in 11 procedures. Of the 12 patients with visual symptoms, ten improved. Of eight patients with hormonal hypersecretion four were cured. Complications included CSF leak (14%), haemorrhage (9%), hemiplegia (5%). There were no mortalities. Experience using the ETTA for pituitary adenomas is limited because it is indicated in highly selected cases (3.1% of our series). An absolute indication is represented by ectopic secreting pituitary stalk/peri-stalk adenomas. ETTA is a useful option in midline frontal adenomas and adenomas with a major extrasellar component, but has a higher morbidity than that seen in the standard transsphenoidal approach. A study comparing ETTA versus transcranial resection is highly desirable.

miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors.

An altered expression of microRNAs (miRNAs) contributes both to the development of cancer and to the progression of the disease. Malignant tumours and tumour cell lines have widespread deregulated expressions of miRNAs compared to normal tissues. In this study, we investigated the expression profiles of 340 mammalian miRNAs in 93 cases of multiform glioblastoma (primary and secondary glioblastoma tumours), by means of DNA microarrays. We show that the expression profiles of 10 miRNAs can distinguish primary from secondary glioblastoma types. Moreover, we found elevated miR-155 levels in primary and secondary glioblastoma tissues as well as in glioblastoma primary cultures. We hypothesised that γ-aminobutyric acid A receptor 1 (GABRA1) is a miR-155 target, and studied the correlation between miR-155 up-regulation and the GABRA1 protein in cultured glioblastoma cells by miRNA silencing. We show that a decrease in miR-155 expression to normal levels restores the expression of GABRA1, making glioblastoma cells sensitive to signals that inhibit cell proliferation mediated by GABRA1. In conclusion, the expression patterns of different miRNAs characterise primary and secondary glioblastomas. The aberrant overexpression of miR-155 contributes to the malignant phenotype of glioblastoma cells removing growth inhibition.

Flow diversion for intracranial aneurysms: a review.

The introduction of flow diverters for treatment of intracranial aneurysms represents a major paradigm shift in the treatment of these lesions. The theoretical hallmark of flow diverters is the treatment of the diseased segment harboring the aneurysm instead of treating the aneurysm itself. Flow diverters are designed to induce disruption of flow near the aneurysm neck while preserving flow into parent vessel and adjacent branches. After flow diversion, intra-aneurysmal thrombosis occurs, followed by shrinkage of the aneurysmal sac as the thrombus organizes and retracts. Preliminary clinical series document effective treatment of wide-neck and/or large and giant aneurysms with acceptable complication rates. However, several questions remain unanswered related to the incidence and mechanisms of aneurysm rupture after treatment with flow diverters, fate of small perforating vessels, and long-term patency rates.

"Real time" angiographic evidence of "pseudoaneurysm" formation after aneurysm rebleeding.

BACKGROUND: Pseudoaneurysms occur at the rupture site of true aneurysms and appear as irregularly shaped and partially thrombosed outpouchings of the main sac. Recanalization of thrombi inside pseudoaneurysmal sac is one of the putative mechanisms of rebleeding of unsecured aneurysms and of coil migration after endovascular treatment. We document "real time" pseudoaneurysm formation after rerupture of an anterior communicating artery aneurysm. METHODS: Case report. RESULTS: A 55-year-old man with aneurysmal subarachnoid hemorrhage from an anterior communicating aneurysm underwent catheter angiography. After the diagnostic angiogram while awaiting for the anesthesia team to proceed with endotracheal general anesthesia, a seizure occurred. Rebleeding was suspected and confirmed by a dynamic CT in the angio suite. A repeat angiogram showed a pseudoaneurysm arising from the previously ruptured aneurysm which had not been present on the original angiogram a few minutes earlier. Uneventful coiling of the aneurysm was undertaken and the patient was discharged home a week later. CONCLUSIONS: We document angiographic formation of a "pseudoaneurysm" at the site of rupture of an anterior communicating artery aneurysm. "Pseudoaneurysm" formation occurs after rupture of an intracranial aneurysm. They represent a weak spot in the aneurysm sac at the site of rupture and probably the result of persistent flow within the clot forming at the site of rupture. Presence of a pseudoaneurysm with characteristic angiographic features like the one herein described represents an unstable area within the aneurysm. This case also highlights the observation that, in patient harboring unsecured ruptured aneurysms, seizures or seizures-like phenomena are the clinical expression of rebleeding unless proven otherwise.

Solid phase subtractive cloning in differentially expressed genes identification.

We developed an array-based subtractive hybridization system for one-step high-throughput subtraction. We printed subtractor RNA up to 10.000 times obtaining an excellent contact surface using a little amount of RNA. During hybridization cDNA, common to subtractor and target samples, remains attached to slide immobilized RNA, leaving free in solution target specific cDNA which after retrieval is cloned.

Jugular tubercle and vertebral artery/posterior inferior cerebellar artery anatomic relationship: a 3-dimensional angiography computed tomography anthropometric study.

OBJECTIVE: To evaluate structural variations of the jugular tubercles (JTs) and their relationships with the vertebral artery, the posterior inferior cerebellar artery (PICA), and the vertebrobasilar junction (VBJ). METHODS: The depth, height, and width of the JTs were measured using 30 cadaveric basicranial specimens and 50 three-dimensional angiography computed tomographic (angio-CT) scans evaluating morphological variations between the 2 sides. Angio-CT analysis evaluated the relationships of the JTs with the vertebral arteries and the PICAs. The location of the VBJ with respect to the JT level in the coronal plane was evaluated. RESULTS: In the cadaveric specimens, the mean JT depth ranged from 0.9 to 3.1 cm, the mean height ranged from 0.6 to 1.5 cm, and the mean width ranged from 0.4 to 1.2 cm. According to the 3-dimensional angio-CT scans, JT measurements ranged as follows: depth, 0.7 to 2.6 cm; height, 0.6 to 1.4 cm; and width, 0.3 to 1.2 cm. The vertebral artery was in close contact with the JT on the left side in 30% of cases and on the right side in 24% of the cases. On axial scans, the PICA origin was classified as anterior to the JT in 20.5% of patients on the left side and 17.4% on the right, at the JT level in 50% of patients on the left side and 45.7% on the right, and posterior to the JT in 29.5% of patients on the left side and 36.9% on the right. On coronal scans, the PICA origin was classified as superior to the JT in 13.6% of patients on the left side and 8.7% on the right, at the JT level in 54.6% of patients on the left side and 50% on the right, and inferior to the JT in 31.8% of patients on the left side and 41.3% on the right. In the coronal plane, the VBJ was located above the tubercles in 16 patients (32%), at the JT level in 28 patients (56%), and below the tubercles in 6 patients (12%). CONCLUSION: A precise morphometric analysis of the JTs on 3-dimensional CT scans was quick and safe and showed significant variations in their size and shape. The relationship of the JT with vertebral artery and the PICA varied significantly, as well as with the VBJ location. Knowledge of these morphological variations can contribute to optimal preoperative surgical planning, minimizing retraction and reducing morbidity during extreme lateral infrajugular-transtubercular exposure surgery.

Molecular genetic analysis in a case of ganglioglioma: identification of a new mutation.

OBJECTIVE: Ganglioglioma is a primary central nervous system low-grade tumor composed of mixed populations of glial and neuroepithelial elements. METHODS: The authors report a case of ganglioglioma in a patient affected by Peutz-Jeghers syndrome, an autosomal dominant disease with varying expressions and incomplete penetrance responsible for an increased risk of gastrointestinal and other malignant tumor forms. RESULTS: The polymerase chain reaction products of exon 6 of STK11/LKB1 showed an abnormal pattern in the single-strand conformation polymorphism analysis. Further sequencing analysis of the exon 6 identified a deletion of T and an insertion of AC at nucleotide 821 causing a shift of the reading frame. The same mutation was found in the patient's peripheral blood. The ribonucleic acid analysis on the ganglioglioma cells revealed an out-of-frame STK11 isoform, characterized by an exon 4 skipping, which resulted in nonsense mediated decay sensitive. CONCLUSION: This report details the molecular genetic analysis of a ganglioglioma that allowed the identification of a new mutation.

Giant craniovertebral junction hemorrhagic schwannoma: case report.

OBJECTIVE: Schwannomas located at the craniovertebral junction are rare. Intratumoral microscopic bleeding may be a common finding, but an acute hemorrhagic presentation is an unusual occurrence. CLINICAL PRESENTATION: We report the case of a 44-year-old woman with acute onset of a hemorrhagic schwannoma of the C2 nerve root. INTERVENTION: An emergency left far-lateral approach and a hemilaminectomy extending from C2 to C5 was performed. The tumor appeared as a dark-reddish subarachnoid mass. Tumor dissection and total removal were achieved by fragmentation and aspiration with an ultrasonic aspirator. A histological examination revealed a schwannoma with a hemorrhagic component. CONCLUSION: Our case highlights the importance of early and proper management of the pathologies of the craniovertebral junction with acute onset. The suspicion of an intratumoral hemorrhagic event must be considered when an acute onset of symptoms is present, even in patients without coagulopathies.