Fluorescence-guided resection using 5ALA is becoming more popular in the neurosurgery of malignant brain tumors. However, this technique has certain limitations, mostly its sensitivity. In this issue of Neuro-Oncology, Valdés, PA et al. reported an ex vivo analysis of PpIX concentrations and their relationship to fluorescence visible to the surgeon. They analyzed 23 patients, including four with WHO grade 1 tumors, two with WHO grade 2 tumors, three with WHO grade 3 tumors, 12 with WHO grade 4 tumors, and two with recurrent gliomas.
They state that “a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. … This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery.” It is widely accepted that resection of malignant tumor cells as much as possible leads to better prognosis of patients with malignant gliomas. Usually, neurosurgeons deliberately state that the tumor was completely removed when the enhanced lesion on Gd-enhanced T1WI disappeared postoperatively. In glioblastoma, probably small numbers of invading remnant cells will not significantly affect the survival time of patients. Wider resection to eradicate invading tumor cells would be performed at the risk of significant brain damage.
In non-enhancing low-grade gliomas (LGGs), neurosurgeons consider the tumor to be completely resected when the high-intensity area of FLAIR images disappears postoperatively. In LGGs, the smaller the number of remnant tumor cells, the better the prognosis of the patients, which may be more significant than in malignant gliomas because the range of invasion would be narrower in LGG. Fluorescence-guided resection may work better to accomplish complete resection.
However, there is another problem: In these LGGs, tumor cells are not necessarily positive for PpIX accumulation. In the Department of Neuro-Oncology/Neurosurgery, International Medical Center, Saitama Medical University, 23% of LGGs were fluorescence positive (Table 1). Valdés, PA et al. also reported that one oligoastrocytoma was positive, whereas the other oligoastrocytoma was negative for fluorescence. In LGG, the problem is not only the sensitivity of the technique as in malignant gliomas but also the fact that not all tumor cells are positive for fluorescence.
Table 1.
Fluorescence-positive gliomas at Saitama Medical University (2008)
| Histologic type | Fluorescence-positive/total (%) |
|---|---|
| Glioblastoma | 46/49 (94) |
| Anaplastic glioma | 14/19 (74) |
| Low-grade glioma | 4/15 (23) |
Still a long way to go …
Reference
- 1.Valdés PA, Kim A, Brantsch M, Niu C, Moses ZB, Tosteson TD, Wilson BC, Paulsen KD, Roberts DW, Harris BT. δ-Aminolevulinic acid-induced protoporphyrin IX concentration correlates with histopathological markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy. Neuro-Oncol. 2011;13 doi: 10.1093/neuonc/nor086. 846–856. [DOI] [PMC free article] [PubMed] [Google Scholar]