Outcome of retreatment for recurrent saccular cerebral aneurysms: a propensity score-matched analysis.
- 作者列表："Matsukawa H","Tanikawa R","Kamiyama H","Noda K","Uchida K","Shirakawa M","Yoshimura S
:Although endovascular or surgical treatment has been performed for preventing the rupture of saccular cerebral aneurysms (sCA), in some patients, the aneurysms may recur and require retreatment. We aimed to investigate the clinical and radiological outcomes of treating recurrent sCA. We retrospectively evaluated the data of 52 patients with 60 recurrent sCAs who were retreated and 1534 patients with 1817 sCAs who received initial treatment. The primary outcome was a recurrence of the aneurysm. Secondary outcomes were an additional treatment, rupture after treatment, and a neurological worsening, which was defined as an increase of 1 or more scores using the modified Rankin Scale at 12-month. Safety outcomes included postoperative ischemic and hemorrhagic complications. We compiled the 120 (60 each) propensity score-matched cohort based on a propensity score for the treatment of recurrent sCA. In the propensity score-matched cohort, recurrence after treatment was observed in 25% and 6.7% of cases in the retreatment and initial treatment groups, respectively. The odds ratio of recurrence after treatment was 4.7 (95% CI, 1.4-15; P = 0.011). The secondary and safety outcomes were not significantly different between the two groups. This study showed that the treatment of recurrent sCA was a risk factor for recurrence after treatment but not for additional treatment, rupture after treatment, or neurological worsening. Although decision-making regarding the treatment varies depending on the institutional protocols and personal experience of the physicians, endovascular or surgical retreatment could be performed without hesitation.
: 虽然已经进行了血管内或手术治疗以防止囊性脑动脉瘤 (sCA) 破裂，但在一些患者中，动脉瘤可能会复发并需要再次治疗。我们旨在研究治疗复发性 sCA 的临床和放射学结局。我们回顾性评估了 52 例 60 例复发 sCAs 患者复治和 1534 例 1817 例 sCAs 初始治疗的资料。主要结果是动脉瘤复发。次要结局是额外治疗、治疗后破裂和神经功能恶化，定义为 12 个月时使用改良 Rankin 量表增加 1 个或更多评分。安全性结局包括术后缺血性和出血性并发症。我们根据治疗复发性 sCA 的倾向评分汇编了 120 (每个 60) 个倾向评分匹配队列。在倾向评分匹配的队列中，再治疗组和初始治疗组分别有 25% 和 6.7% 的病例观察到治疗后复发。治疗后复发的比值比为 4.7 (95% CI，1.4 ~ 15; p = 0.011)。两组的次要和安全性结局无显著差异。本研究表明，复发性 sCA 的治疗是治疗后复发的危险因素，但不是额外治疗、治疗后破裂或神经功能恶化的危险因素。虽然关于治疗的决策因医生的机构方案和个人经验而异，但可以毫不犹豫地进行血管内或外科再治疗。
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.