Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications.

Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery

Diagnostic and surgical management of primary central nervous system angioleiomyoma: A case report and literature review

Angioleiomyoma (ALM) is a benign smooth muscle neoplasm that mainly occurs in lower extremities subcutaneous tissue and generally affects middle-aged adults. This tumor histotype may rarely localize intracranially, although only a few cases have been described in the literature. We report a case of intracranial ALM, whose differential diagnosis has been particularly challenging, and firstly provide a comprehensive radiological and intra-operative evaluation of a such rare entity. This represents also the first report of the use of intraoperative confocal microscopy in ALM and the first documented short-term recurrence. At this regard, a scoping literature review has been conducted with the aim of presenting the major clinical and diagnostic features along with the proposed therapeutic strategies

Exoscopic-assisted posterior approach for the removal of thoracic dumbbell schwannoma: Three-dimensional operative video

“Dumbbell” tumors are described as benign neoplasms presenting both intraspinal and extraspinal extensions, connected through the intervertebral foramen (McCormick, 1996) [1]. About 90 % of such tumors are histologically classified as schwannomas that most frequently arise in the thoracic region (Takamura and et al., 1997) [2]. Diagnosis is usually achieved as soon as the dimensional increase of the intracanal portion results in nerve or spinal cord compression (Ishikawa and et al., 2002) [3]. How to obtain a complete surgical resection of tumors with large or ventrally located extraforaminal components with a minimally invasive approach is still debated (Payer and et al., 2006) [4]. The single-stage posterior removal of the tumor is the most performed approach for lesions presenting with a small extra-foraminal component (Payer and et al., 2006) [4]. However, due to the reduced visual surgical field and poor control of the surrounding structures that could be obtained with an operative microscopic (OM) view, the application of this approach still appears to be limited to lesions with a large extraspinal component. An alternative surgical approach is the lateral transthoracic transpleural approach, which, however, carries greater risks of complications and often requires assistance from a thoracic surgeon.During the last decade, the exoscope was developed as a hybrid optical instrument, standing between the OM and the endoscope, merging the pros and cons of both visualization technologies, providing a wide viewing angle, high-resolution images, and non-monoaxial view.In this work we present a case of a 60-years old male patient with a 6-month history of dorsal pain and mild left limb paresthesia resistant to conservative treatment in which for the first time a single stage exoscopic-assisted (Olympus ORBEYE 4K-3D exoscope) posterior approach was used to remove entirely a thoracic dumbbell schwannoma with large extraspinal involvement

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review

The issue: Gliomas are primary tumors arising from supporting cells of the central nervous system (CNS), usually in the brain. The 2021 World Health Organization (WHO) classifies gliomas as adult-type diffuse gliomas or circumscribed astrocytic gliomas depending on their histology and molecular features. Spinal astrocytic gliomas are very rare, and nowadays no standard of therapy is available. Treatment options are limited: surgery is often not radical, and adjuvant therapies include mostly radiotherapy (RT) or systemic chemotherapy (CHT). There is lack of knowledge about the efficacy and safety of therapies and their multidisciplinary approaches. The aim of the review: A systematic review of the literature from January 2000 to June 2021 was performed, including both clinical trials and observational studies on histological adult primary spinal cord astrocytomas (SCA), with a minimum follow-up of 6 months and reporting the overall survival, progression-free survival or clinical neurological outcome after any therapeutic approach (surgery, RT or CHT). What are the main findings? A total of 1197 citations were identified by the Medline search and additional records; based on our inclusion criteria, 18 studies were included with a total of 285 adult patients. We documented the lack of any clinical trial. What are the conclusions? The available literature data are limited to series/retrospective studies, including heterogeneous patients, i.e., astrocytoma as well as ependymoma or pediatric/adult age, with scanty data on the outcomes of interest. No clinical trials have been run. Due to the rarity of this disease, multicentric clinical trials with molecular investigations are mandatory to better manage such a rare disease

Table_1_Confocal laser imaging in neurosurgery: A comprehensive review of sodium fluorescein-based CONVIVO preclinical and clinical applications.docx

Given the established direct correlation that exists among extent of resection and postoperative survival in brain tumors, obtaining complete resections is of primary importance. Apart from the various technological advancements that have been introduced in current clinical practice, histopathological study still remains the gold-standard for definitive diagnosis. Frozen section analysis still represents the most rapid and used intraoperative histopathological method that allows for an intraoperative differential diagnosis. Nevertheless, such technique owes some intrinsic limitations that limit its overall potential in obtaining real-time diagnosis during surgery. In this context, confocal laser technology has been suggested as a promising method to have near real-time intraoperative histological images in neurosurgery, thanks to the results of various studies performed in other non-neurosurgical fields. Still far to be routinely implemented in current neurosurgical practice, pertinent literature is growing quickly, and various reports have recently demonstrated the utility of this technology in both preclinical and clinical settings in identifying brain tumors, microvasculature, and tumor margins, when coupled to the intravenous administration of sodium fluorescein. Specifically in neurosurgery, among different available devices, the ZEISS CONVIVO system probably boasts the most recent and largest number of experimental studies assessing its usefulness, which has been confirmed for identifying brain tumors, offering a diagnosis and distinguishing between healthy and pathologic tissue, and studying brain vessels. The main objective of this systematic review is to present a state-of-the-art summary on sodium fluorescein-based preclinical and clinical applications of the ZEISS CONVIVO in neurosurgery.</p

Sporadic and von Hippel–Lindau Related Hemangioblastomas of Brain and Spinal Cord: Multimodal Imaging for Intraoperative Strategy

Hemangioblastomas (HBs) are rare, benign tumors often related to von Hippel–Lindau disease. They represent the most frequent primary cerebellar tumors in adults. Neurosurgical procedures aim to obtain a gross-total resection of tumor nodules, avoiding intra-postoperative hemorrhage. The introduction of new intraoperative imaging techniques has considerably changed surgical strategies in neuro-oncology. We present an overview of clinical and radiological data of a mono-institutional retrospective cohort, focusing on the role of intraoperative multimodal imaging in surgical strategy. From 2015 to 2021, we identified 64 (81%) cranial (42 cerebellar, 8 supratentorial, and 14 of the brainstem) HBs and 15 (19%) spinal (4 cervical and 11 dorsal) HBs in 79 patients. Intraoperatively, indocyanine green videoangiography with FLOW800 was used in 62 cases (52 cranial and 10 spinal), intraoperative ultrasound and contrast-enhanced ultrasounds in 22 cases (18 cranial and 4 spinal HBs), and fluorescein in 10 cases (in 6 cranial and 2 spinal cases used as SF-VA). Gross total resection was achieved in 100% of the cases (53 mural nodule removal and 26 complete resections of the solid tumor). No side effects were reported following the combination of these tools. Multimodal intraoperative techniques provide valuable and reliable information to identify the tumor and its vasculature, guiding a more precise and safer resection and reducing the risk of recurrence

Fluorescein-guided surgery for the resection of pilocytic astrocytomas: A multicentric retrospective study

ObjectivePilocytic astrocytomas (PAs) are relatively benign tumors, usually enhancing on post-contrast MRI and often characterized by a mural nodule within a cystic component. Surgical resection represents the mainstay of treatment, and extent of resection (EOR) is associated with improved survival. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of these circumscribed astrocytic gliomas. MethodsSurgical databases at two neurosurgical departments (Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy and Department of Neurosurgery, University Medical Center Regensburg, Regensburg, Germany) were retrospectively reviewed to identify the cohort of patients with pilocytic astrocytoma who had undergone fluorescein-guided tumor resection at any of the centers between March 2016 and February 2022. SF was intravenously injected (5 mg/kg) immediately after the induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW 560 filter (Carl Zeiss Meditec, Oberkochen, Germany). ResultsForty-four patients (25 males and 19 females; 26 pediatric patients, mean age of 9.77 years, range 2 to 17 years; and 18 adult patients, mean age of 34.39 years, range 18 to 58 years) underwent fluorescein-guided surgery. No side effects related to SF occurred. In all tumors, contrast enhancement on preoperative MRI was correlated with intense, heterogeneous yellow fluorescence with bright fluorescent cystic fluid. Fluorescein was considered helpful in distinguishing tumors from viable tissue in all cases except three patients due to faint fluorescein enhancement. Biopsy was intended in two operations, and partial resection was intended in three operations. Gross total resection was achieved in 24 cases out of 39 patients scheduled for tumor removal (61.54%), in five cases a minimal residual volume was highlighted by postoperative MRI despite the intraoperative subjective evaluation of complete tumor removal (12.82%); in the other 10 cases, the resection was subtotal with fluorescent residual spots to avoid neurological worsening (25.64%). ConclusionsThe use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data showed a positive effect of fluorescein-guided surgery on intraoperative visualization during resection of Pas, suggesting a possible role in improving the extent of resection of these lesions

Towards an Established Intraoperative Oncological Favorable Tool: Results of Fluorescein-Guided Resection from a Monocentric, Prospective Series of 93 Primary Glioblastoma Patients

It is commonly reported that maximizing surgical resection of contrast-enhancing regions in patients with glioblastoma improves overall survival. Efforts to achieve an improved rate of resection have included several tools: among those, the recent widespread of fluorophores. Sodium fluorescein is an unspecific, vascular dye which tends to accumulate in areas with an altered blood–brain barrier. In this retrospective analysis of patients prospectively enrolled in the FLUOCERTUM study, we aimed to assess the role of fluorescein-guided surgery on surgical radicality, survival, and morbidity. A retrospective review based on 93 consecutively and prospectively enrolled IDH wild-type glioblastoma patients (2016–2022) was performed; fluorescence characteristics, rate of resection, clinical outcome, and survival were analyzed. No side effect related to fluorescein occurred; all of the tumors presented a strong yellow-green enhancement and fluorescein was judged fundamental in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 77 cases out of 93 patients (82.8%). After a mean follow-up time of 17.4 months (3–78 months), the median progression-free survival was 12 months, with a PFS-6 and PFS-12 of 94.2% and 50%, respectively, whereas median overall survival was estimated to be 16 months; survival at 6, 12, and 24 months was 91.8%, 72.3%, and 30.1%, respectively. Based on these results, we can assert that the fluorescein-guided technique is a safe and valuable method for patients harboring a newly diagnosed, untreated glioblastoma

The Role of Bypass Surgery for the Management of Complex Intracranial Aneurysms in the Anterior Circulation in the Flow-Diverter Era: A Single-Center Series

Despite the increasing popularity of flow diverters (FDs) as an endovascular option for intracranial aneurysms, the treatment of complex aneurysms still represents a challenge. Combined strategies using a flow-preservation bypass could be considered in selected cases. In this study, we retrospectively reviewed our series of patients with complex intracranial aneurysms submitted to bypass. From January 2015 to May 2022, 23 patients were selected. We identified 11 cases (47.8%) of MCA, 6 cases (26.1%) of ACA and 6 cases (26.1%) of ICA aneurysms. The mean maximal diameter was 22.73 ± 12.16 mm, 8 were considered as giant, 9 were fusiform, 8 presented intraluminal thrombosis, 10 presented wall calcification, and 18 involved major branches or perforating arteries. Twenty-five bypass procedures were performed in 23 patients (two EC–IC bypasses with radial artery graft, seventeen single- or double-barrel STA–MCA bypasses and six IC–IC bypasses in anterior cerebral arteries). The long-term bypass patency rate was 94.5%, and the total aneurysm exclusion was 95.6%, with a mean follow-up of 28 months. Median KPS values at last follow-up was 90, and a favorable outcome (KPS ≥ 70 and mRS ≤ 2) was obtained in 87% of the cases. The use of bypass techniques represents, in selected cases, a valid therapeutic option in the management of complex anterior circulation aneurysms when a simpler direct approach, including the use of FD, is considered not feasible

Are Thalamic Intrinsic Lesions Operable? No-Man’s Land Revisited by the Analysis of a Large Retrospective, Mono-Institutional, Cohort

Thalamic gliomas represent a heterogeneous subset of deep-seated lesions for which surgical removal is advocated, although clear prognostic factors linked to advantages in performance status or overall survival are still lacking. We reviewed our Institutional Cancer Registry, identifying patients who underwent surgery for thalamic gliomas between 2006 and 2020. Associations between possible prognostic factors such as tumor volume, grade, the extent of resection and performance status (PS), and overall survival (OS) were evaluated using univariate and multivariate survival analyses. We found 56 patients: 31 underwent surgery, and 25 underwent biopsy. Compared to biopsy, surgery resulted positively associated with an increase in the OS (hazard ratio, HR, at multivariate analysis 0.30, 95% confidence interval, CI, 0.12–0.75). Considering the extent of resection (EOR), obtaining GTR/STR appeared to offer an OS advantage in high-grade gliomas (HGG) patients submitted to surgical resection if compared to biopsy, although we did not find statistical significance at multivariate analysis (HR 0.53, 95% CI 0.17–1.59). Patients with a stable 3-month KPS after surgery demonstrated to have a better prognosis in terms of OS if compared to biopsy (multivariate HR 0.17, 95% CI, 0.05–0.59). Age and histological grades were found to be prognostic factors for this condition (p = 0.04 and p = 0.004, respectively, chi-square test). Considering the entire cohort, p53 positivity (univariate HR 2.21, 95% CI 1.01–4.82) and ATRX positivity (univariate HR 2.69, 95% CI 0.92–7.83) resulted associated with a worse prognosis in terms of OS. In this work, we demonstrated that surgery aimed at tumor resection might offer a stronger survival advantage when a stable 3-month KPS after surgery is achieved