Kamp Marcel A, Felsberg Jörg, Sadat Hosai, Kuzibaev Jamshid, Steiger Hans-Jakob, Rapp Marion, Reifenberger Guido, Dibué Maxiné, Sabel Michael
Department of Neurosurgery, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany,
Acta Neurochir (Wien). 2015 Feb;157(2):207-13; discussion 213-4. doi: 10.1007/s00701-014-2313-4. Epub 2014 Dec 30.
The 5-aminolevulinic acid (5-ALA) fluorescence-guided resection of recurrent malignant glioma is a standard surgical procedure at many neuro-oncological centers and is considered to be equally reliable as the primary resection of these tumors. 5-ALA induced fluorescence (5-AIF)-guided resection has been demonstrated to be highly predictive for tumor tissue. As pseudoprogression and radiation-induced necrosis are critical differential diagnoses of glioma recurrence, the purpose of the present analysis was to analyze 5-AIF behavior in resected tissue specimens histopathologically showing regressive and reactive changes but lacking active, that is, cellular recurrent tumor tissue after adjuvant treatment of malignant glioma.
A retrospective analysis was performed in patients suffering from malignant glioma who underwent surgical resection for suspected contrast-enhancing tumor recurrence (according to RANO criteria) at our institution between 2007 and 2013, but in whom histopathological analysis only revealed reactive changes. The presence of AIF in the resected tissue samples was intraoperatively assessed and classified by the surgeon, using the categories (1) no, (2) vague and (3) solid AIF.
A total of 13 out of 313 patients who underwent AIF-guided surgical resection of tissue suspicious for recurrent glioma histologically demonstrated only reactive changes without active recurrent tumor tissue after adjuvant therapy. Pretreatment was chemotherapy with temozolomide in 1 patient and combined radio-/chemotherapy in 12 patients. Six patients had suffered previous tumor recurrence with a subsequently intensified adjuvant therapy. Seven of the 13 patients displayed solid, 5 patients vague and 1 patient no 5-AIF of the resected tissue specimens. However, all 5-AIF-positive lesions exhibited heterogeneous fluorescence patterns with vaguely or solidly fluorescent as well as nonfluorescent regions.
Resection of reactive tissue without active recurrent tumor after multimodal treatment for glioblastoma is frequently associated with solid or vague 5-AIF. Therefore, neurosurgeons should remain cautious when attempting to employ intraoperative 5-AIF to discriminate radiation- and chemotherapy-induced tissue changes from true disease progression. Nevertheless, 5-AIF-guided resection remains a valid tool in the neurosurgical treatment of recurrent gliomas.
5-氨基乙酰丙酸（5-ALA）荧光引导下切除复发性恶性胶质瘤是许多神经肿瘤中心的标准手术方法，并且被认为与这些肿瘤的初次切除同样可靠。5-ALA诱导荧光（5-AIF）引导下切除已被证明对肿瘤组织具有高度预测性。由于假性进展和放射性坏死是胶质瘤复发的关键鉴别诊断，本分析的目的是在组织病理学上显示退行性和反应性改变但缺乏活跃的（即细胞性复发性肿瘤组织）恶性胶质瘤辅助治疗后的切除组织标本中分析5-AIF的表现。
对2007年至2013年间在本机构因疑似对比增强肿瘤复发（根据RANO标准）接受手术切除的恶性胶质瘤患者进行回顾性分析，但组织病理学分析仅显示反应性改变。手术中由外科医生对切除组织样本中AIF的存在进行评估并分类，使用的类别为（1）无，（2）模糊和（3）实性AIF。
在313例接受AIF引导下对疑似复发性胶质瘤组织进行手术切除的患者中，共有13例在组织学上仅显示反应性改变，辅助治疗后无活跃的复发性肿瘤组织。1例患者的预处理为替莫唑胺化疗，12例患者为联合放化疗。6例患者曾有肿瘤复发，随后强化了辅助治疗。13例患者中有7例切除组织标本显示实性5-AIF，5例显示模糊5-AIF，1例显示无5-AIF。然而，所有5-AIF阳性病变均表现出异质性荧光模式，有模糊或实性荧光区域以及非荧光区域。
胶质母细胞瘤多模式治疗后切除无活跃复发性肿瘤的反应性组织常与实性或模糊的5-AIF相关。因此，神经外科医生在试图利用术中5-AIF区分放疗和化疗引起的组织变化与真正的疾病进展时应保持谨慎。尽管如此，5-AIF引导下切除仍然是复发性胶质瘤神经外科治疗中的一种有效工具。
