Boucher Y, Salehi H, Witwer B, Harsh G R, Jain R K
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Br J Cancer. 1997;75(6):829-36. doi: 10.1038/bjc.1997.148.
Fluid transport parameters in intracranial tumours influence the delivery of therapeutic agents and the resolution of peritumoral oedema. The tumour and cortex interstitial fluid pressure (IFP) and the cerebrospinal fluid pressure (CSFP) were measured during the growth of brain and pial surface tumours [R3230AC mammary adenocarcinoma (R3230AC) and F98 glioma (F98)] in rats. Intratumoral and intracranial pressures were also measured in rodents and patients treated with dexamethasone, mannitol and furosemide (DMF), and hypocapnia. The results show that (1) for the R3230AC on the pial surface, IFP increased with tumour volume and CSFP increased exponentially for tumours occupying a brain volume of 5% or greater; (2) in F98 with volumes of approximately 10 mm3, IFP decreased from the tumour to the cortex, whereas for tumour volumes > 16 mm3 IFP equilibrates between F98 and the cortex; (3) DMF treatment reduced the IFP of intraparenchymal tumours significantly and induced a pressure gradient from the tumour to the cortex; and (4) in 11 patients with intracranial tumours, the mean IFP was 2.0 +/- 2.5 mmHg. In conclusion, the IFP gradient between intraparenchymal tumours and the cortex decreases with tumour growth, and treatment with DMF can increase the pressure difference between the tumour and surrounding brain. The results also suggest that antioedema therapy in patients with brain tumours is responsible in part for the low tumour IFP.
颅内肿瘤中的液体传输参数会影响治疗药物的递送以及瘤周水肿的消退。在大鼠脑和软脑膜表面肿瘤[R3230AC乳腺腺癌(R3230AC)和F98胶质瘤(F98)]生长过程中,测量了肿瘤和皮质的间质液压力(IFP)以及脑脊液压力(CSFP)。还在接受地塞米松、甘露醇和呋塞米(DMF)治疗以及低碳酸血症治疗的啮齿动物和患者中测量了瘤内和颅内压力。结果表明:(1)对于软脑膜表面的R3230AC肿瘤,IFP随肿瘤体积增加,而对于占据脑体积5%或更大的肿瘤,CSFP呈指数增加;(2)对于体积约为10 mm³的F98肿瘤,IFP从肿瘤向皮质降低,而对于肿瘤体积>16 mm³的情况,IFP在F98和皮质之间达到平衡;(3)DMF治疗显著降低了实质内肿瘤的IFP,并诱导了从肿瘤到皮质的压力梯度;(4)在11例颅内肿瘤患者中,平均IFP为2.0±2.5 mmHg。总之,实质内肿瘤与皮质之间的IFP梯度随肿瘤生长而降低,DMF治疗可增加肿瘤与周围脑组织之间的压力差。结果还表明,脑肿瘤患者的抗水肿治疗部分导致了肿瘤低IFP。