Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection.

BACKGROUND: Sodium fluorescein (fluorescein) crosses a disrupted blood-brain barrier similarly to gadolinium contrast in contrast-enhancing cerebral tumors. When exposed to light with 560 nm wavelength during surgery, fluorescein emits a yellow-green fluorescent light that can be visualized through an operating microscope equipped with an appropriate emission filter. The distribution of the fluorescence correlates with the contrast on a gadolinium contrast-enhanced MRI. OBJECTIVE: The objective of this single-center retrospective study was to investigate if the use of fluorescein would increase the extent of resection and to examine if fluorescein guided resection influences postoperative neurological status. METHODS: During the study period from August 2014 to August 2018, 117 patients were operated for cerebral metastases. Of these, 56 operations were guided by fluorescein and 61 by traditional white light. All patients had an early postoperative MRI within 72 h after surgery. RESULTS: The use of fluorescein increased the extent of resection in patients with cerebral metastases. The use of fluorescein was not associated with increased postoperative sequelae or neurological damage regardless of underlying primary cancer. CONCLUSION: Fluorescein is a helpful supplement in the neurosurgical treatment of cerebral metastases.

[Endoscopic evacuation of deep intracerebral spontaneous haematoma].

Deep-seated intracerebral spontaneous haematomas (ICHs) pose a neurosurgical challenge in decision-making process as summarised in this review. No studies have been able to demonstrate a significant effect on surgical removal. The challenge to surgical removal is the damage the surgery causes to the healthy brain in connection with the surgical procedure. The application of minimally invasive techniques in the form of endoscopic removal of deep-seated ICHs, results in significantly less "trauma" to the healthy brain and hopefully a better prognosis for patients with deep-seated spontaneous ICHs.

Orthostatic hypotension after cervicomedullary junction surgery: illustrative case.

BACKGROUND: Surgery at the cervicomedullary junction carries a risk of damaging vital brainstem functions. Because the nucleus of the solitary tract (NS) is involved in the baroreceptor reflex, damage to its integrity may lead to orthostatic hypotension. OBSERVATIONS: A 56-year-old man with a medical history of hypertension, von Hippel-Lindau disease, and previous bilateral adrenalectomy due to pheochromocytoma was referred with symptoms of dysphagia and paralysis of the left vocal cord. Paralysis of the left vagus nerve was suspected. Magnetic resonance imaging revealed a contrast-enhancing cystic process in the cervicomedullary junction. Twenty-three years earlier, the patient had undergone surgical treatment for a hemangioblastoma in the same region. After repeated surgery, the patient temporarily developed orthostatic hypotension. At discharge, the patient no longer needed antihypertensive medication. LESSONS: Surgery near the cervicomedullary junction can affect the NS, leading to disruption of the baroreceptor response that regulates blood pressure.

Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study.

OBJECTIVE: Maximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes. METHODS: A total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression-free survival and overall survival were analyzed using an adjusted Cox proportional hazards model. RESULTS: One hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03). CONCLUSIONS: Fluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

Frameless stereotactic neuronavigated biopsy: A retrospective study of morbidity, diagnostic yield, and the potential of fluorescence: A single-center clinical investigation.

OBJECTIVE: The primary objective of this retrospective study was to evaluate the diagnostic yield and morbidity/mortality associated with frameless stereotactic neuronavigated intracranial biopsies with and without the use of fluorescein. PATIENTS AND METHODS: Patient cases from January 2007 to December 2017 were identified using the ICD-10 procedure code AAG00. Relevant clinical data, including histological diagnosis, were collected retrospectively from the electronic patient charts and independently reviewed by two authors. RESULTS: 111 biopsies obtained from 103 patients were identified. Of these, 109 biopsies yielded a diagnosis and resulted in a diagnostic yield of 98.2%. Fluorescein was used in 13 biopsies (11.7%). Twelve patients (10.8%) experienced postoperative complications, and the mortality attributed to the surgery was 1.8%. In 12.6% of cases, the biopsies showed inflammation or nonspecific reactive changes. No statistically significant differences were observed in diagnostic yield or number and severity of complications according to whether intraoperative histological examination was used or not. CONCLUSION: Although direct comparisons between studies are difficult due to lack of consensus about the definition of diagnostic yield, the present study reports a similar diagnostic yield to other studies. Intraoperative histopathological analysis appeared to give little extra benefit.

Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been associated with poor prognosis and resistance towards chemotherapy in several cancer forms. In a previous study we found an association between a low TIMP-1 tumor immunoreactivity and increased survival for glioblastoma patients, when compared to moderate and high TIMP-1 tumor immunoreactivity. The aim of the present study was to further evaluate TIMP-1 as a biomarker in gliomas by studying TIMP-1 gene copy numbers by fluorescence in situ hybridization (FISH) on 33 glioblastoma biopsies and by measuring levels of TIMP-1 in plasma obtained pre-operatively from 43 patients (31 gliomas including 21 glioblastomas) by enzyme-linked immunosorbent assay (ELISA). The results showed TIMP-1 gene copy numbers per cell ranging from 1 to 5 and the TIMP-1/CEN-X ratio ranging between 0.7 and 1.09, suggesting neither amplification nor loss of the TIMP-1 gene. The TIMP-1 protein levels measured in plasma were not significantly higher than TIMP-1 levels measured in healthy subjects. No correlation was identified between TIMP-1 tumor cell immunoreactivities and the TIMP-1 gene copy numbers or the plasma TIMP-1 levels. In conclusion, high immunohistochemical TIMP-1 protein levels in glioblastomas were not caused by TIMP-1 gene amplification and TIMP-1 in plasma was low and not directly related to tumor TIMP-1 immunoreactivity. The study suggests that TIMP-1 immunohistochemistry is the method of choice for future clinical studies evaluating TIMP-1 as a biomarker in glioblastomas.

Invasion of primary glioma- and cell line-derived spheroids implanted into corticostriatal slice cultures.

Gliomas are highly invasive tumors and the pronounced invasive features of gliomas prevent radical surgical resection. In the search for new therapeutics targeting invasive glioma cells, in vivo-like in vitro models are of great interest. We developed and evaluated an in vivo-like in vitro model preserving the invasive features and stem cell features of glioma cells. Fluorescently labelled primary glioma spheroids and U87MG cell line-derived spheroids were implanted into organotypic rat corticostriatal slice cultures and the invasion was followed over time by confocal microscopy. The invasion was validated immunohistochemically with paraffin sections using a human-specific vimentin antibody. Moreover, the preservation of immature stem cell features was evaluated immunohistochemically using the stem cell markers CD133, Sox2, Bmi-1 and nestin. The confocal and immunohistochemical results showed that the primary glioma spheroid area was constant or decreasing after implantation, with a clear increase in the number of invading cells over time. In contrast, the U87MG spheroid area increased after implantation, with no convincing tumor cell invasion. High levels of Bmi-1 and nestin were found in all spheroids, whereas high levels of Sox2 and low to moderate levels of CD133 were only found in the primary spheroids. In conclusion, the invasion of gliomas is preserved using primary glioma spheroids. Some stem cell features are preserved as well, making this model useful in drug development elucidating both invasion and cancer stemness at the early in vitro level.