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Eric Suero Molina, Johannes Wölfer, Christian Ewelt, André Ehrhardt, Benjamin Brokinkel and Walter Stummer

OBJECTIVE

Fluorescence guidance with 5–aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue.

METHODS

The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System).

RESULTS

Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection.

CONCLUSIONS

Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

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Eric Suero Molina, Christian Ewelt, Nils Warneke, Michael Schwake, Michael Müther, Stephanie Schipmann and Walter Stummer

OBJECTIVE

Recent efforts to improve visualization of 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PPIX) fluorescence resulted in a dual-labeling technique, combining it with fluorescein sodium in a prototype setup. Fluorescein identifies regions with blood-brain barrier breakdown in gliomas. However, normally perfused and edematous brain fluoresces unselectively, with strong background enhancement. The aim of this study was to test the feasibility of a novel, integrated filter combination using porphyrins for selective tumor identification and fluorescein for background enhancement.

METHODS

A microscope with a novel built-in filter system (YB 475) for visualizing both fluorescein and 5-ALA–induced porphyrins was used. Resection limits were identified with the conventional BLUE 400 filter system. Six patients harboring contrast ring-enhancing lesions were analyzed.

RESULTS

The complete surgical field could now be illuminated. Fluorescein was helpful for improving background visualization, and enhancing dura, edematous tissue, and cortex. Overlapping regions with both fluorophores harbored merged orange fluorescence. PPIX fluorescence was better visualized, even in areas beyond a normal working distance of approximately 25 cm, where the BLUE 400 filters recognized no or weak fluorescence.

CONCLUSIONS

The novel filter system improved general tissue brightness and background visualization, enhancing fluorescence-guided tumor resection. Furthermore, it appears promising from a scientific perspective, enabling the simultaneous and direct observation of areas with blood-brain barrier breakdown and PPIX fluorescence.

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Eric Jose Suero Molina, Thomas Niederstadt, Vincent Ruland, Gian Kayser, Walter Stummer, Christian Ewelt and Jochen Rössler

Patients with Gorham-Stout disease (GSD), a rare disease of poorly understood etiopathophysiology, suffer from progressive osteolysis. Destruction of bone matrix is caused by lymphatic vessels, which can lead to CSF leakage if parts of bony structures adjacent to CSF spaces are involved. So far, fewer than 200 patients have been reported in the literature; only 4 of these patients presented with CSF leakage. The authors report the case of a 30-year-old man with GSD and CSF leakage due to dura mater involvement after progression of an osteolytic lesion in the thoracic spine. Neurosurgical intervention, including dura repair, was needed. Experimental medical therapy with rapamycin was started, leading to disease control for more than 12 months. Progression of GSD can lead to destruction of the meninges, causing CSF leakage. The authors review 4 other cases reported in the literature and discuss therapeutic options.

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Eric Suero Molina, Stephanie Schipmann, Isabelle Mueller, Johannes Wölfer, Christian Ewelt, Matthias Maas, Benjamin Brokinkel and Walter Stummer

OBJECTIVE

Awake craniotomies have become a feasible tool over time to treat brain tumors located in eloquent regions. Different techniques have been applied in neurooncology centers. Both “asleep-awake-asleep” (asleep) and “conscious sedation” were used subsequently at the authors’ neurosurgical department. Since 2013, the authors have only performed conscious sedation surgeries, predominantly using the α2-receptor agonist dexmedetomidine as the anesthetic drug. The aim of this study was to compare both mentioned techniques and evaluate the clinical use of dexmedetomidine in the setting of awake craniotomies for glioma surgery.

METHODS

The authors retrospectively analyzed patients who underwent operations either under the asleep condition using propofol-remifentanil or under conscious sedation conditions using dexmedetomidine infusions. In the asleep group patients were intubated with a laryngeal mask and extubated for the assessment period. Adverse events, as well as applied drugs with doses and frequency of usage, were recorded.

RESULTS

From 224 awake surgeries between 2009 and 2015, 180 were performed for the resection of gliomas and included in the study. In the conscious sedation group (n = 75) significantly fewer opiates (p < 0.001) and vasoactive (p < 0.001) and antihypertensive (p < 0.001) drugs were used in comparison with the asleep group (n = 105). Furthermore, the postoperative length of stay (p < 0.001) and the surgical duration (p < 0.001) were significantly lower in the conscious sedation group.

CONCLUSIONS

Use of dexmedetomidine creates excellent conditions for awake surgeries. It sedates moderately and acts as an anxiolytic. Thus, after ceasing infusion it enables quick and reliable clinical neurological assessment of patients. This might lead to reducing the amount of administered antihypertensive and vasoactive drugs as well as the length of hospitalization, while likely ensuring more rapid surgery.

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Sebastian Lohmann, Tobias Brix, Julian Varghese, Nils Warneke, Michael Schwake, Eric Suero Molina, Markus Holling, Walter Stummer and Stephanie Schipmann

OBJECTIVE

Various quality indicators are currently under investigation, aiming at measuring the quality of care in neurosurgery; however, the discipline currently lacks practical scoring systems for accurately assessing risk. The aim of this study was to develop three accurate, easy-to-use risk scoring systems for nosocomial infections, reoperations, and adverse events for patients with cerebral and spinal tumors.

METHODS

The authors developed a semiautomatic registry with administrative and clinical data and included all patients with spinal or cerebral tumors treated between September 2017 and May 2019. Patients were further divided into development and validation cohorts. Multivariable logistic regression models were used to develop risk scores by assigning points based on β coefficients, and internal validation of the scores was performed.

RESULTS

In total, 1000 patients were included. An unplanned 30-day reoperation was observed in 6.8% of patients. Nosocomial infections were documented in 7.4% of cases and any adverse event in 14.5%. The risk scores comprise variables such as emergency admission, nursing care level, ECOG performance status, and inflammatory markers on admission. Three scoring systems, NoInfECT for predicting the incidence of nosocomial infections (low risk, 1.8%; intermediate risk, 8.1%; and high risk, 26.0% [p < 0.001]), LEUCut for 30-day unplanned reoperations (low risk, 2.2%; intermediate risk, 6.8%; and high risk, 13.5% [p < 0.001]), and LINC for any adverse events (low risk, 7.6%; intermediate risk, 15.7%; and high risk, 49.5% [p < 0.001]), showed satisfactory discrimination between the different outcome groups in receiver operating characteristic curve analysis (AUC ≥ 0.7).

CONCLUSIONS

The proposed risk scores allow efficient prediction of the likelihood of adverse events, to compare quality of care between different providers, and further provide guidance to surgeons on how to allocate preoperative care.

Free access

Stephanie Schipmann, Michael Müther, Louise Stögbauer, Sebastian Zimmer, Benjamin Brokinkel, Markus Holling, Oliver Grauer, Eric Suero Molina, Nils Warneke and Walter Stummer

OBJECTIVE

High-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.

METHODS

After 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.

RESULTS

Twenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4–5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8–7.2 months).

CONCLUSIONS

Combined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.