Analysis of 5-aminolevulinic acid–induced fluorescence in 55 different spinal tumors

Object Subtotal resection (STR) of spinal tumors can result in tumor recurrence. Currently, no clinically reliable marker is available for intraoperative visualization of spinal tumor tissue. Protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) is capable of visualizing malignant gliomas. Fluorescence-guided resections of malignant cerebral gliomas using 5-ALA have resulted in an increased rate of complete tumor removal. Recently, the application of 5-ALA has also been described in the first cases of spinal tumors. Therefore, the aim of this observational study was to systematically investigate 5-ALA–induced fluorescence characteristics in different spinal tumor entities. Methods Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of PpIX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification. Results Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy. Conclusions In this study, 5-ALA–PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA–induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci.

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NF2 and Spinal Tumors

Journal of Neurosurgery Spine ◽

10.3171/spi.2006.5.2.179 ◽

2006 ◽

Vol 5 (2) ◽

pp. 179 ◽

Cited By ~ 1

Author(s):

Dilys M. Parry

Keyword(s):

Spinal Tumor ◽

Spinal Tumors ◽

Fisher Exact Test ◽

Radiological Progression ◽

Intramedullary Tumors ◽

Exact Test ◽

Extramedullary Tumor ◽

Clinical Records ◽

And Behavior

Object The authors conducted a study to examine the incidence, classification, and progression of spinal tumors in patients with neu-rofibromatosis Type 2 (NF2) treated at a single center, and to examine relationships with the known mutational subtypes of NF2. Methods They performed a retrospective review of clinical records, neuroimaging studies, and genetic data obtained in 61 patients with NF2. Forty-one (67%) of 61 patients harbored one or more spinal tumors. Thirty-four patients had undergone serial spinal magnetic resonance imaging during a mean follow-up period of 52 months (range 10–103 months; median 53 months). In 16 patients there were multiple extramedullary tumors smaller than 5 mm, which did not progress. Fourteen patients harbored at least one extramedullary tumor that was greater than 5 mm; of these, radiological progression was demonstrated or spinal tumor excision was performed during the follow-up period in eight cases (57%). Eleven patients harbored intramedullary cord tumors in addition to small and large extramedullary tumors, three (27%) of which exhibited radiological progression. In cases in which genotypes were known, protein-truncating mutations were significantly more likely to be associated with the presence of spinal tumors than in other types (p = 0.03, Fisher exact test). No associations between clinical behavior of spinal tumors and genotype, however, could be demonstrated. Conclusions Spinal tumors in cases involving NF2 are heterogeneous in type, distribution, and behavior but larger-size tumors are more likely to progress significantly. Intramedullary tumors usually accompany multiple extramedullary tumors. In the authors' experience subtyping of the NF2 mutation has not yet influenced management. Protein-truncating mutations are associated with an increased prevalence of spinal tumors.

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5-ALA fluorescence for intraoperative visualization of spinal ependymal tumors and identification of unexpected residual tumor tissue: experience in 31 patients

Journal of Neurosurgery Spine ◽

10.3171/2020.6.spine20506 ◽

2020 ◽

pp. 1-9

Author(s):

Matthias Millesi ◽

Barbara Kiesel ◽

Vanessa Mazanec ◽

Lisa I. Wadiura ◽

Adelheid Wöhrer ◽

...

Keyword(s):

White Light ◽

Tumor Recurrence ◽

Tumor Tissue ◽

Aminolevulinic Acid ◽

Residual Tumor ◽

Incomplete Resection ◽

Intramedullary Tumors ◽

Resection Cavity ◽

Increased Risk ◽

Intraoperative Visualization

OBJECTIVEGross-total resection (GTR) is the treatment of choice in the majority of patients suffering from spinal ependymal tumors. In such tumors, the extent of resection (EOR) is considered the key factor for tumor recurrence and thus patient prognosis. However, incomplete resection is not uncommon and leads to increased risk of tumor recurrence. One important cause of incomplete resection is insufficient intraoperative visualization of tumor tissue as well as residual tumor tissue. Therefore, the authors investigated the value of 5-aminolevulinic acid (5-ALA)–induced fluorescence in a series of spinal ependymal tumors for improved tumor visualization.METHODSAdult patients who underwent preoperative 5-ALA administration and surgery for a spinal ependymal tumor were included in this study. For each tumor, a conventional white-light microsurgical resection was performed. Additionally, the fluorescence status (strong, vague, or no fluorescence) and fluorescence homogeneity (homogenous or inhomogeneous) of the spinal ependymal tumors were evaluated during surgery using a modified neurosurgical microscope. In intramedullary tumor cases with assumed GTR, the resection cavity was investigated for potential residual fluorescing foci under white-light microscopy. In cases with residual fluorescing foci, these areas were safely resected and the corresponding samples were histopathologically screened for the presence of tumor tissue.RESULTSIn total, 31 spinal ependymal tumors, including 27 intramedullary tumors and 4 intradural extramedullary tumors, were included in this study. Visible fluorescence was observed in the majority of spinal ependymal tumors (n = 25, 81%). Of those, strong fluorescence was noted in 23 of these cases (92%), whereas vague fluorescence was present in 2 cases (8%). In contrast, no fluorescence was observed in the remaining 6 tumors (19%). Most ependymal tumors demonstrated an inhomogeneous fluorescence effect (17 of 25 cases, 68%). After assumed GTR in intramedullary tumors (n = 15), unexpected residual fluorescing foci within the resection cavity could be detected in 5 tumors (33%). These residual fluorescing foci histopathologically corresponded to residual tumor tissue in all cases.CONCLUSIONSThis study indicates that 5-ALA fluorescence makes it possible to visualize the majority of spinal ependymal tumors during surgery. Unexpected residual tumor tissue could be detected with the assistance of 5-ALA fluorescence in approximately one-third of analyzed intramedullary tumors. Thus, 5-ALA fluorescence might be useful to increase the EOR, particularly in intramedullary ependymal tumors, in order to reduce the risk of tumor recurrence.

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Pediatric spinal pilomyxoid astrocytoma

Journal of Neurosurgery Pediatrics ◽

10.3171/2013.8.peds1397 ◽

2013 ◽

Vol 12 (5) ◽

pp. 511-516 ◽

Cited By ~ 3

Author(s):

Sarah T. Garber ◽

Robert J. Bollo ◽

Jay K. Riva-Cambrin

Keyword(s):

Treatment Guidelines ◽

Alkylating Agents ◽

Malignant Gliomas ◽

Spinal Tumor ◽

Total Resection ◽

Who Grade ◽

Thoracic Spinal Cord ◽

Pilomyxoid Astrocytoma ◽

Treatment Regimens ◽

Thoracic Spinal

Pediatric spinal pilomyxoid astrocytoma (PMA) is an extremely rare tumor that merits recognition as a specific, unique entity. The authors present the case of an intramedullary PMA in the thoracic spinal cord of an 11-year-old boy who presented with back pain, scoliosis, and multiple lung nodules. The patient underwent T5–11 laminoplasty and near-total resection of the spinal tumor. The final pathological diagnosis was WHO Grade II PMA. The patient did well for 14 months until the tumor progressed both clinically and radiographically. A literature review focusing on the clinical characteristics, histology, and treatment of PMAs provides a better understanding of these rare lesions. Because of the small number of cases optimal treatment guidelines have not been established, but gross-total resection and adjuvant chemotherapy with alkylating agents appear to confer a better long-term prognosis. Pediatric patients with PMAs can remain recurrence free at least 5 years after surgery, although these tumors may disseminate or dedifferentiate into more malignant gliomas. Recognition of intramedullary PMA as a unique entity in children is vital to the development of specific surgical and adjuvant treatment regimens.

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Unilateral laminectomy approach for total resection of intradural extramedullary spinal tumor

Neurologico Spinale Medico Chirurgico ◽

10.36444/nsmc.v2i1.5 ◽

2019 ◽

Vol 2 (2) ◽

pp. 23-26

Author(s):

Steven Awyono ◽

Putu Eka Mardhika ◽

Tjokorda Gde Bagus Mahadewa ◽

Akbar Wido ◽

Hizkia Lumban Gaol ◽

...

Keyword(s):

Recovery Time ◽

Spinal Tumor ◽

Spinal Tumors ◽

Fast Recovery ◽

Spinal Cord Tumors ◽

Total Resection ◽

Central Nervous System Neoplasm ◽

The Central Nervous System ◽

Intradural Extramedullary ◽

Care Period

Spinal tumors found in about 5-15% of the central nervous system neoplasm. Intradural-extramedullary spinal cord tumors are one of the types that usually managed with total laminectomy but with many postoperative complications. A 76-year-old woman with paraplegia caused by intradural-extramedullary intraspinal tumor at thoracic 4 level. For this patient, we performed unilateral laminectomy without any fusion or stabilization from the left side then we performed total excision of the tumor. The surgery was successfully done with fast improvement of patient condition, minimal pain after surgery, no blood transfusion needed, shorter intensive care period needed, and fast recovery time are the prominent things in this case. Three days after surgery, the patient’s motoric power already improved and then the patient is permitted to go home at the fifth day.

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Characterization of autofluorescence and quantitative protoporphyrin IX biomarkers for optical spectroscopy-guided glioma surgery

Scientific Reports ◽

10.1038/s41598-021-99228-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

David Black ◽

Sadahiro Kaneko ◽

Anna Walke ◽

Simone König ◽

Walter Stummer ◽

...

Keyword(s):

Aminolevulinic Acid ◽

Protoporphyrin Ix ◽

Blue Shift ◽

Spectral Unmixing ◽

Proliferation Index ◽

Low Grade ◽

Glioma Surgery ◽

Ki 67 ◽

Who Grade

Abstract5-Aminolevulinic acid (5-ALA)-mediated fluorescence does not effectively depict low grade gliomas (LGG) or the infiltrative tumor portion of high-grade gliomas (HGG). While spectroscopy improves sensitivity and precision, this is currently limited by autofluorescence and a second protoporphyrin IX (PpIX) fluorescence state at 620 nm. We investigated the autofluorescence to better characterize the present spectra and thus increase PpIX quantification precision and sensitivity. This study included 128 patients undergoing surgery for malignant glioma. 5-ALA (Gliolan) was administered before anesthesia, and fluorescence was measured using a hyperspectral device. It was found that all 2692 measured spectra consisted of contributions from 620 to 634 nm PpIX, NADH, lipofuscin, and flavins. The basis spectra were characterized and their use in spectral unmixing led to 82.4% lower fitting error for weakly fluorescing areas (p < 0.001), and 92.3% fewer false positive tumor identifications in control measurements (p = 0.0065) compared to previous works. They also decreased the PpIX620 contribution, thus halving the mean Ratio620/634 (p < 0.001). The ratio was approximately 0 for HGGs and increasing for LGGs, as demonstrated previously. Additionally, the Ratio620/634, the MIB-1/Ki-67 proliferation index, and the PpIX peak blue-shift were found to be significantly related to WHO grade, fluorescence visibility, and PpIX contribution (p < 0.001), and the value of these three as quantitative biomarkers is discussed.

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Hypericin and 5-aminolevulinic acid-induced protoporphyrin IX induce enhanced phototoxicity in human endometrial cancer cells with non-coherent white light

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2009.02.001 ◽

2009 ◽

Vol 6 (1) ◽

pp. 12-18 ◽

Cited By ~ 19

Author(s):

Xiaoye Schneider-Yin ◽

Aida Kurmanaviciene ◽

Marion Roth ◽

Malgorzata Roos ◽

André Fedier ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Cells ◽

White Light ◽

Aminolevulinic Acid ◽

Protoporphyrin Ix

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Use of Intraoperative CO2 Laser for the Resection of a Ventral Intradural Extramedullary Cervical Spinal Tumor: 2-Dimensional Operative Video

Operative Neurosurgery ◽

10.1093/ons/opz171 ◽

2019 ◽

Vol 18 (5) ◽

pp. E161-E161

Author(s):

Joseph A Osorio ◽

Guillermo Victorino T Liabres ◽

Catherine A Miller ◽

Michael W McDermott ◽

Praveen V Mummaneni

Keyword(s):

Spinal Cord ◽

Co2 Laser ◽

Tumor Resection ◽

Spinal Tumor ◽

Cord Compression ◽

Spinal Tumors ◽

Laser Technique ◽

Who Grade ◽

Patient Consent ◽

Intradural Extramedullary

Abstract Ventral spinal tumors are surgically challenging because the tumor resection should minimize spinal cord and nerve root manipulation to minimize morbidity, while providing access to a complete tumor resection. The CO2 laser has been useful in resection of central nervous system tumors, but little is described about the method used to resect spinal tumors.1 This video demonstrates the removal of a ventral cervical spinal meningioma using the CO2 laser. A 62-yr-old man presented with progressive paresthesias, gait instability, and urinary frequency. A 1-cm intradural extramedullary mass at C5 showed severe spinal cord compression. Patient consent was obtained prior to performing the procedure. A posterior lateral approach is shown, with a bone removal corridor created at C5 for accessing the tumor ventrally. A right-sided facetectomy and pediculectomy at C5 were performed being flush with the posterior vertebral body. A dural opening positioned laterally provided a working corridor between C5 and C6 nerve rootlets. Lateral portions of tumor were excised in wedge-shaped slices starting laterally and working medially. These slices created a successive and enlarging space to safely allow piecemeal tumor dissection and removal, while limiting retraction upon the spinal cord. The CO2 laser was used to cauterize the tumor capsule, create wedge resections of tumor, and coagulate the final dural attachment. The pathology was a meningioma WHO Grade I. The patient did well, with resolution of parasthesias and ataxia. The CO2 laser technique allowed for limited spinal cord retraction throughout the tumor resection and gross total resection of the tumor was achieved.

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The role of indocyanine green videoangiography with FLOW 800 analysis for the surgical management of central nervous system tumors: an update

Neurosurgical FOCUS ◽

10.3171/2018.3.focus1862 ◽

2018 ◽

Vol 44 (6) ◽

pp. E6 ◽

Cited By ~ 13

Author(s):

Francesco Acerbi ◽

Ignazio G. Vetrano ◽

Tommaso Sattin ◽

Camilla de Laurentis ◽

Lorenzo Bosio ◽

...

Keyword(s):

Blood Flow ◽

Indocyanine Green ◽

Surgical Management ◽

Tumor Resection ◽

Cns Tumors ◽

Spinal Tumors ◽

Surgical Removal ◽

Indocyanine Green Videoangiography ◽

Intramedullary Tumors ◽

Flow 800

OBJECTIVEIndocyanine green videoangiography (ICG-VA) is an intraoperative technique used to highlight vessels in neurovascular surgery. Its application in the study of the vascular pathophysiology in CNS tumors and its role in their surgical management are still rather limited. A recent innovation of ICG-VA (i.e., the FLOW 800 algorithm integrated in the surgical microscope) allows a semiquantitative evaluation of cerebral blood flow. The aim of this study was to evaluate for the first time the systematic application of ICG-VA and FLOW 800 analysis during surgical removal of CNS tumors.METHODSBetween May 2011 and December 2017, all cases in which ICG-VA and FLOW 800 analysis were used at least one time before, during, or after the tumor resection, and in which surgical videos were available, were retrospectively reviewed. Results of the histological analysis were analyzed together with the intraoperative ICG-VA with FLOW 800 in order to investigate the tumor-related videoangiographic features.RESULTSSeventy-one patients who underwent surgery for cerebral and spinal tumors were intraoperatively analyzed using ICG-VA with FLOW 800, either before or after tumor resection, for a total of 93 videoangiographic studies. The histological diagnosis was meningioma in 25 cases, glioma in 14, metastasis in 7, pineal region tumor in 5, hemangioblastoma in 4, chordoma in 3, and other histological types in 13 cases. The authors identified 4 possible applications of ICG-VA and FLOW 800 in CNS tumor surgery: extradural surveys allowed exploration of sinus patency and the course of veins before dural opening; preresection surveys helped in identifying pathological vascularization (arteriovenous fistulas and neo-angiogenesis) and regional venous outflow, and in performing temporary venous clipping tests, when necessary; postresection surveys were conducted to evaluate arterial and venous patency and parenchymal perfusion after tumor removal; and a premyelotomy survey was conducted in intramedullary tumors to highlight the posterior median sulcus.CONCLUSIONSThe authors found ICG-VA with FLOW 800 to be a useful method to monitor blood flow in the exposed vessels and parenchyma during microsurgical removal of CNS tumors in selected cases. In particular, a preresection survey provides useful information about pathophysiological changes of brain vasculature related to the tumor and aids in the individuation of helpful landmarks for the surgical approach, and the postresection survey helps to prevent potential complications associated with the resection (such as local hypoperfusion or venous infarction).

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