5 aminolevulinic acid fluorescence guided resection of spinal tumor

Multiple studies have attempted to evaluate the utility of 5-ALA-aided resection of spinal neoplasms.

Wainwright et al., from the Westchester Medical CenterTohoku University Hospital, reviewed the existing literature on the use of 5-ALA and PpIXfluorescence as an aid to resection of primary and secondary spinal neoplasms by searching the PUBMED and EMBASE database for records up to March 2018. Data was abstracted from all studies describing spinal neurosurgical uses in the English language.

In the reviewed studies, the most useful fluorescence was observed in meningiomas, ependymomas, drop metastases from cerebral gliomas, and spinal hemangiopericytoma, which is consistent with applications in cerebral neoplasms.

The available literature is significantly limited by a lack of standardized methods for measurement and quantification of 5-ALA fluorescence. The results of the reviewed studies should guide future development of rational trial protocols for the use of 5-ALA guided resection in spinal neoplasms1).


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 Protoporphyrin IX 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.

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.

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 2).


A study included 10 patients who underwent surgical resection of an intramedullary ependymoma. Nine patients were orally administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA fluorescence was visualized with an operating microscope. Tumors were removed in a standardized manner with electrophysiological monitoring. The extent of resection was evaluated on the basis of intraoperative findings and postoperative magnetic resonance imaging. Histopathological diagnosis was established according to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki-67 labeling index.

5-ALA fluorescence was positive in 7 patients (6 grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative findings were dichotomized: Tumors covered by the cyst were easily separated from the normal parenchyma, whereas tumors without the cyst appeared to be continuous to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in delineating the ventral and cranial and caudal margins. Ki-67 labeling index was significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases. All patients improved neurologically or stabilized after surgery.

5-ALA fluorescence was useful for detecting tumor margins during surgery for intramedullary ependymoma. When combined with electrophysiological monitoring, fluorescence-guided resection could help to achieve maximum tumor resection safely 3).

References

1)

Wainwright JV, Endo T, Cooper JB, Tominaga T, Schmidt MH. The role of 5-aminolevulinic acid in spinal tumor surgery: a review. J Neurooncol. 2018 Dec 29. doi: 10.1007/s11060-018-03080-0. [Epub ahead of print] Review. PubMed PMID: 30594965.
2)

Millesi M, Kiesel B, Woehrer A, Hainfellner JA, Novak K, Martínez-Moreno M, Wolfsberger S, Knosp E, Widhalm G. Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus. 2014 Feb;36(2):E11. doi: 10.3171/2013.12.FOCUS13485. PubMed PMID: 24484249.
3)

Inoue T, Endo T, Nagamatsu K, Watanabe M, Tominaga T. 5-aminolevulinic acid fluorescence-guided resection of intramedullary ependymoma: report of 9 cases. Neurosurgery. 2013 Jun;72(2 Suppl Operative):ons159-68; discussion ons168. doi: 10.1227/NEU.0b013e31827bc7a3. PubMed PMID: 23149963.

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