Clinical and Radiological Outcomes of Intracranial Aneurysm Clipping Aided by Transit Time Flowmetry.
- 作者列表："Van Lanen RHGJ","Jacobi-Postma LAA","Veersema TJ","Teernstra OPM","Dings JTA
BACKGROUND:Since the International Subarachnoid Aneurysm Trial, coiling has been favored over clipping for intracranial aneurysms, resulting in selection of increasingly complex aneurysm configurations for clipping. We present the outcomes of clipping of aneurysms not suitable for coiling, with transit time flowmetry technology to aid monitoring of intraoperative flow. METHODS:All consecutive patients surgically treated for intracranial aneurysms were included. We assessed intraoperative arterial blood flow in relation to postoperative ischemia and unfavorable outcome (modified Rankin Scale score 3-6), along with radiological occlusion rate, at 6 months and 1 year after surgery. RESULTS:Mortality at 1 year was 7.9%, with a 21.6% rate of an unfavorable outcome. Almost all (96.1%) of patients with unruptured aneurysms had an favorable outcome at 1 year, compared with 71.9% of patients with aneurysmal subarachnoid hemorrhage. Postoperative computed tomography imaging showed an 86.7% occlusion rate and a 7.5% rate of clip-related ischemia. Flow <40% of baseline significantly predicted clip-related ischemia (odds ratio [OR], 5.14; 95% confidence interval [CI], 1.41-8.4; P = 0.012). Clip reposition aided by transit time flowmetry resulted in restored flow >50% above baseline flow in 85.7% of aneurysms. Less than 50% flow from baseline was an independent predictor of unfavorable outcome (OR, 3.85; 95% CI, 1.6-9.0; P = 0.001), along other risk factors. CONCLUSION:In this study of clinical and radiological outcomes of surgically treated cerebral aneurysms not suitable for unassisted coiling, we showed positive results for these challenging aneurysms, aided by transit time flowmetry as a valuable tool, providingquantitative measurements of arterial blood flow to help achieve optimal clip placement and minimizing aneurysm residuals that may be sites of rebleeding. Adequate flow, defined as ≥50% of baseline, greatly reduces the risk of unfavorable outcome.
背景: 自国际蛛网膜下动脉瘤试验以来，弹簧圈栓塞术一直被青睐于颅内动脉瘤的夹闭术，导致越来越复杂的动脉瘤构型被选择用于夹闭术。我们介绍了不适合弹簧圈栓塞的动脉瘤夹闭的结局，采用了传输时间流量测定技术来帮助监测术中流量。 方法: 纳入所有因颅内动脉瘤手术治疗的连续患者。我们评估了术中动脉血流与术后缺血和不良结局的关系 (改良 Rankin 量表评分 3-6)，以及术后 6 个月和 1 年的放射学闭塞率。 结果: 1 年死亡率为 7.9%，不良结局率为 21.6%。与 96.1% 的动脉瘤性蛛网膜下腔出血患者相比，几乎所有 (71.9%) 的未破裂动脉瘤患者在 1 年时有良好的预后。术后计算机断层扫描成像显示 86.7% 的闭塞率和 7.5% 的夹相关缺血率。50% 的动脉瘤中流量高于基线流量 85.7%。相对于基线流量小于 50% 是不良结局的独立预测因子 (OR，3.85; 95% CI，1.6-9.0; P = 0.001) 以及其他危险因素。 结论: 在这项不适合非辅助弹簧圈栓塞手术治疗的脑动脉瘤的临床和影像学结果的研究中，我们对这些具有挑战性的动脉瘤显示了积极的结果，通过时间流量测定作为一种有价值的工具。提供动脉血流的定量测量，以帮助实现最佳的夹闭放置，最大限度地减少可能是再出血部位的动脉瘤残留。足够的流量，定义为 ≥ 基线的 50%，大大降低了不良结局的风险。
METHODS:PURPOSE:To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS:Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS:The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION:The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.
METHODS:BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.
METHODS:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue. MAIN BODY:The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities. SHORT CONCLUSIONS:On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.