Marhold Franz, Mercea Petra A, Scheichel Florian, Berghoff Anna S, Heicappell Patricia, Kiesel Barbara, Mischkulnig Mario, Borkovec Martin, Wolfsberger Stefan, Woehrer Adelheid, Preusser Matthias, Knosp Engelbert, Ungersboeck Karl, Widhalm Georg
1Department of Neurosurgery, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria.
2Department of Neurosurgery, Medical University of Vienna, Austria.
J Neurosurg. 2019 Sep 27;133(4):1032-1043. doi: 10.3171/2019.6.JNS1997. Print 2020 Oct 1.
Incomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort.
Adult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria.
Altogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well.
In this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.
由于术中对肿瘤组织的可视化不足,脑转移瘤(BM)的神经外科手术切除不完全是一项重大临床挑战,可能导致局部复发。最近,首次在BM患者中报道了可见的5-氨基乙酰丙酸(5-ALA)诱导荧光。因此,本研究的目的是首次系统地调查5-ALA荧光在一大群患者中对BM术中可视化的价值。
在两个专业神经外科中心前瞻性招募术前给予5-ALA后进行疑似BM切除术的成年患者(≥18岁)。手术期间,研究每个BM的荧光状态(可见或无荧光)、荧光质量(强、模糊或无)和荧光均匀性(均匀或不均匀)。此外,BM的这些特定荧光特征与原发肿瘤类型和组织病理学亚型相关。根据当前的WHO 2016标准建立肿瘤诊断。
总共154例患者的157个BM接受了手术治疗。104个BM(66%)观察到可见荧光,其余53例(34%)无荧光。详细而言,53个肿瘤(34%)显示强荧光,51个肿瘤(32%)显示模糊荧光,53个肿瘤(34%)无荧光。大多数BM(84%的病例)表现出不均匀的荧光模式。根据原发肿瘤,与所有其他肿瘤相比,黑色素瘤BM中可见荧光的频率较低(p = 0.037)。根据组织病理学亚型,导管乳腺癌BM中可见荧光比所有其他亚型更常见(p = 0.008)。值得注意的是,在111例研究病例中的74例(67%)BM切除后,周围脑组织中也观察到可见荧光。
在迄今为止最大的系列研究中,三分之二的BM检测到可见的5-ALA荧光。然而,特征性的不均匀荧光模式和频繁缺乏强荧光限制了5-ALA在BM中的应用,因此该技术需要进一步改进。