Yin Zhuang, Jun Lin and Huilin Yang
Ali Liu, Jun-Mei Wang, Gui-Lin Li, Yi-Lin Sun, Shi-Bin Sun, Bin Luo and Mei-Hua Wang
The goal of this study was to assess the clinical and pathological features of benign brain tumors that had been treated with Gamma Knife surgery (GKS) followed by resection.
In this retrospective chart review, the authors identified 61 patients with intracranial benign tumors who had undergone neurosurgical intervention after GKS. Of these 61 patients, 27 were male and 34 were female; mean age was 49.1 years (range 19–73 years). There were 24 meningiomas, 18 schwannomas, 14 pituitary adenomas, 3 hemangioblastomas, and 2 craniopharyngiomas. The interval between GKS and craniotomy was 2–168 months, with a median of 24 months; for 7 patients, the interval was 10 years or longer. For 21 patients, a craniotomy was performed before and after GKS; in 9 patients, pathological specimens were obtained before and after GKS. A total of 29 patients underwent GKS at the Beijing Tiantan Hospital. All specimens obtained by surgical intervention underwent histopathological examination.
Most patients underwent craniotomy because of tumor recurrence and/or exacerbation of clinical signs and symptoms. Neuroimaging analyses indicated tumor growth in 42 patients, hydrocephalus in 10 patients with vestibular schwannoma, cystic formation with mass effect in 7 patients, and tumor hemorrhage in 13 patients, of whom 10 had pituitary adenoma. Pathological examination demonstrated that, regardless of the type of tumor, GKS mainly induced coagulative necrosis of tumor parenchyma and stroma with some apoptosis and, ultimately, scar formation. In addition, irradiation induced vasculature stenosis and occlusion and tumor degeneration as a result of reduced blood supply. GKS-induced vasculature reaction was rarely observed in patients with pituitary adenoma. Pathological analysis of tumor specimens obtained before and after GKS did not indicate increased tumor proliferation after GKS.
Radiosurgery is effective for intracranial benign tumors of small size and deep location and for tumor recurrence after surgical intervention; it is not effective for intracranial tumors with symptomatic mass effect. The radiobiological effects of stereotactic radiosurgery on the benign tumors are mainly caused by cellular and vascular mechanisms. Among the patients in this study, high-dose irradiation did not increase tumor proliferation. GKS can induce primary and secondary effects in tumors, which could last more than 10 years, thereby warranting long-term follow-up after GKS.
Fuxin Lin, Yuming Jiao, Jun Wu, Bing Zhao, Xianzeng Tong, Zhen Jin, Yong Cao and Shuo Wang
The impact of functional MRI (fMRI)–guided navigation on the surgical outcome of patients with arteriovenous malformations (AVMs) is undetermined. This large, randomized controlled trial (RCT) was designed to determine the safety and efficacy of fMRI-guided microsurgery of AVMs. This paper reports the preliminary results of the interim analysis.
Between September 2012 and June 2015, eligible patients were randomized to the standard microsurgery group (control group) or the fMRI-guided surgery group (experimental group) in a 1:1 ratio. Patients in the control group underwent conventional digital subtraction angiography and MRI before surgery. The surgery was performed according to the standard procedure. However, patients in the experimental group underwent blood oxygen level–dependent (BOLD) fMRI and diffusion tensor imaging within 1 week before surgery. Moreover, preoperative eloquent brain tissue mapping and intraoperative fMRI navigation were performed in addition to the standard procedure. The preliminary end points were the total removal rate of AVMs and postoperative surgical complications. The primary end points were modified Rankin Scale (mRS) score (favorable: mRS Score 0–2; poor: mRS Score 3–6) and surgery-related permanent functional deficits (S-PFD) at the last clinic visit (≥ 6 months). Statistical analysis was performed using the statistical package from SPSS.
The interim analysis included 184 participants (93 in the experimental group and 91 in the control group). Patients were equally distributed between the 2 groups. Neither the preliminary nor the primary end points, including postoperative complications (p = 0.781), residual AVM (p = 1.000), last mRS score (p = 0.654), and S-PFD (p = 0.944) showed any significant difference between the control and experimental group. According to the results of the univariate analysis, eloquent adjacent brain tissue (OR 0.14; 95% CI 0.06–0.32; p < 0.001), large size of the nidus (OR 1.05; 95% CI 1.02–1.08; p = 0.002), or diffuse nidus (OR 3.05; 95% CI 1.42–6.58; p = 0.004) were all significantly associated with S-PFD. Additionally, a high Spetzler-Martin score (OR 3.54; 95% CI 2.08–6.02; p < 0.001), no previous hemorrhage (OR 2.35; 95% CI 1.00–5.54; p = 0.05), or a low preoperative mRS score (OR 0.42; 95% CI 0.17–1.00; p = 0.049) were also significantly associated with S-PFD. Multivariate analysis revealed that independent factors correlated with S-PFD were eloquent adjacent brain tissue (OR 0.17; 95% CI 0.04–0.70; p = 0.014) and low preoperative mRS score (OR 0.22; 95% CI 0.07–0.69; p = 0.009).
This preplanned interim analysis revealed no significant differences in the primary end points between the experimental and control group, prompting an early termination of this RCT. The preliminary data indicated that the additional intervention of fMRI navigation is not associated with a more favorable surgical outcome in patients with AVMs. The results indicated that eloquent adjacent brain tissue and a low preoperative mRS score are independent risk factors for S-PFD.
Clinical trial registration no.: NCT01758211 (clinicaltrials.gov)
Fuxin Lin, Bing Zhao, Jun Wu, Lijun Wang, Zhen Jin, Yong Cao and Shuo Wang
Case selection for the surgical treatment of arteriovenous malformations (AVMs) of the eloquent motor area remains challenging. The aim of this study was to determine the risk factors for worsened muscle strength after surgery in patients with this disorder.
At their hospital the authors retrospectively studied 48 consecutive patients with AVMs involving motor cortex and/or the descending pathway. All patients had undergone preoperative functional MRI (fMRI) and diffusion tensor imaging (DTI), followed by resection. Both functional and angioarchitectural factors were analyzed with respect to the change in muscle strength. Functional factors included lesion-to-corticospinal tract distance (LCD) on DTI and lesion-to-activation area distance (LAD) and cortical reorganization on fMRI. Based on preoperative muscle strength, the changes in muscle strength at 1 week and 6 months after surgery were defined as short-term and long-term surgical outcomes, respectively. Statistical analysis was performed using the statistical package SPSS (version 20.0.0, IBM Corp.).
Twenty-one patients (43.8%) had worsened muscle strength 1 week after surgery. However, only 10 patients (20.8%) suffered from muscle strength worsening 6 months after surgery. The LCD was significantly correlated with short-term (p < 0.001) and long-term (p < 0.001) surgical outcomes. For long-term outcomes, patients in the 5 mm ≥ LCD > 0 mm (p = 0.009) and LCD > 5 mm (p < 0.001) categories were significantly associated with a lower risk of permanent motor worsening in comparison with patients in the LCD = 0 mm group. No significant difference was found between patients in the 5 mm ≥ LCD > 0 mm group and LCD > 5 mm group (p = 0.116). Nidus size was the other significant predictor of short-term (p = 0.021) and long-term (p = 0.016) outcomes. For long-term outcomes, the area under the ROC curve (AUC) was 0.728, and the cutoff point was 3.6 cm. Spetzler-Martin grade was not associated with short-term surgical outcomes (0.143), although it was correlated with long-term outcomes (0.038).
An AVM with a nidus in contact with tracked eloquent fibers (LCD = 0) and having a large size is more likely to be associated with worsened muscle strength after surgery in patients with eloquent motor area AVMs. Surgical treatment in these patients should be carefully considered. In patients with an LCD > 5 mm, radical resection may be considered to eliminate the risk of hemorrhage.
Hung-Chen Wang, Tzu-Ming Yang, Wei-Che Lin, Yu-Jun Lin, Nai-Wen Tsai, Chia-Wei Liou, Aij-Lie Kwan and Cheng-Hsien Lu
Increased plasma nuclear and mitochondrial DNA levels have been reported in critically ill patients, and extracellular DNA may originate from damaged tissues having undergone necrosis. This study tested the hypothesis that nuclear and mitochondrial DNA levels in CSF and plasma are substantially increased in patients with acute spontaneous aneurysmal subarachnoid hemorrhage (SAH) and decrease thereafter, such that nuclear and mitochondrial DNA levels may be predictive of treatment outcomes.
Serial nuclear and mitochondrial DNA levels in CSF and plasma from 21 adult patients with spontaneous aneurysmal SAH and 39 healthy volunteers who received myelography examinations during the study period were evaluated.
Data showed that circulating plasma nuclear DNA concentrations and both nuclear and mitochondrial DNA levels in CSF significantly increased in patients with aneurysmal SAH on admission compared with the volunteers. In patients with poor outcome, the CSF nuclear and mitochondrial DNA levels were significantly higher on Days 1 and 4, and plasma nuclear DNA levels were significantly higher from Day 8 to Day 14. Higher CSF nuclear (> 85.1 ng/ml) and mitochondrial DNA levels (> 31.4 ng/ml) on presentation were associated with worse outcome in patients with aneurysmal SAH.
Higher CSF DNA levels on presentation, rather than plasma DNA levels, are associated with worse outcomes in patients with acute spontaneous aneurysmal SAH. More prospective multicenter investigations are needed to confirm the predictive value of CSF and plasma DNA levels on outcome.
Da Li, Shu-Yu Hao, Liang Wang, Gui-Lin Li, Jun-Mei Wang, Zhen Wu, Li-Wei Zhang, Jun-Ting Zhang and Wang Jia
Medulloepithelioma (MEPL) is a rare, malignant primitive neuroectodermal tumor with dismal survival rates. The authors aimed to define independent risk factors for progression-free survival (PFS) and overall survival (OS) and to propose an optimal treatment protocol for MEPL.
The authors reviewed the clinicoradiological data obtained in 12 patients with MEPL who underwent surgical treatment at their institution between January 2008 and June 2016. In addition, they reviewed 55 cases of MEPL published in the literature from January 1957 to July 2017. A pooled analysis of individual patient data of these 67 patients was performed to evaluate risk factors.
The authors’ cohort included 5 males and 7 females with a mean age of 15.7 years. Gross-total resection (GTR) was achieved in 10 (83.3%) patients. Radiotherapy (mean total dose 42.8 Gy) and chemotherapy were administered to 7 and 4 patients, respectively. After a median follow-up of 21.7 months, 6 (50%) patients suffered recurrence and subsequently died, with median PFS and OS times of 5.5 and 13.9 months, respectively. Among the 55 patients in the literature, 13 (23.6%) patients received GTR, and 25 (49.0%) and 15 (29.4%) received radiotherapy (median total dose 53.2 Gy) and chemotherapy, respectively. After a median follow-up of 10.0 months, the recurrence and mortality rates were 69.7% (23/33) and 70.8% (34/48), respectively, and the median PFS was 6.0 months. Of the pooled cohort, the actuarial 5-year PFS and OS were 36.3% and 29.2%, respectively, and the estimated median survival time for PFS and OS were 12.8 and 15.2 months, respectively. A multivariate Cox model verified non-GTR (HR 5.537, p < 0.001) and no radiotherapy (HR 3.553, p = 0.008) as independent adverse factors for PFS. The 5-year PFS in patients with or without GTR was 63.8% and 6.3%, respectively, and in patients with or without radiotherapy was 42.7% and 23.1%, respectively. A multivariate model demonstrated non-GTR (HR 9.089, p < 0.001), no radiotherapy (HR 3.126, p = 0.004), and no chemotherapy (HR 3.621, p = 0.004) as independent adverse factors for poor OS. The 5-year OS in patients with GTR, radiotherapy, or chemotherapy was 72.1%, 44.0%, and 58.0%, respectively. In contrast, in patients without GTR, radiotherapy, or chemotherapy, the 5-year OS was 5.8%, 14.3%, and 15.8%, respectively. Overall, in patients receiving GTR plus chemoradiotherapy, the actuarial 5-year PFS and OS were both 87.5%.
MEPL is a rare neoplastic entity with a poor prognosis. There are no distinguishing radiological features apart from cystic degeneration. Via the pooled analysis, the authors identified independent adjustable factors associated with PFS and OS, from which they advocate for GTR plus chemoradiotherapy with a sufficient dose if tolerable as an optimal treatment to improve outcomes. Future studies with large cohorts will be necessary to verify our findings.
Jian-Cong Weng, Da Li, Liang Wang, Zhen Wu, Jun-Mei Wang, Gui-Lin Li, Wang Jia, Li-Wei Zhang and Jun-Ting Zhang
Intracranial giant cell tumors (GCTs) are extremely rare neoplasms with dismal survival and recurrence rates. The authors aimed to confirm independent adverse factors for progression-free survival (PFS) and to propose an optimal treatment algorithm.
The authors reviewed the clinical data of 43 cases of intracranial GCTs in their series. They also reviewed 90 cases of previously reported GCTs in the English language between 1982 and 2017 using Ovid MEDLINE, Embase, PubMed, and Cochrane databases with keywords of “giant cell tumor” or “osteoclastoma” and “skull,” “skull base,” “temporal,” “frontal,” “sphenoid,” or “occipital.” These prior publication data were processed and used according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Aforementioned risk factors for the authors’ series and the pooled cases were evaluated in patients not lost to follow-up (m = 38 and n = 128, respectively).
The authors’ cohort included 28 males and 15 females with a mean age of 30.5 years. Gross-total resection (GTR) was achieved in 15 (34.9%) patients. Fifteen patients (39.5%) who did not undergo GTR received postoperative radiotherapy with a mean total dose of 54.7 ± 4.1 Gy. After a mean follow-up of 71.3 months, 12 (31.6%) patients experienced recurrence, and 4 (10.5%) died of disease. The actuarial 5-year PFS and overall survival (OS) were 68.6% and 90.0% in the authors’ cohort, respectively. A multivariate Cox regression analysis verified that partial resection (HR 7.909, 95% CI 2.296–27.247, p = 0.001), no radiotherapy (HR 0.114, 95% CI 0.023–0.568, p = 0.008), and Ki-67 ≥ 10% (HR 7.816, 95% CI 1.584–38.575, p = 0.012) were independent adverse factors for PFS. Among the 90 cases in the literature, GTR was achieved in 49 (54.4%) cases. Radiotherapy was administered to 33 (36.7%) patients with a mean total dose of 47.1 ± 5.6 Gy. After a mean follow-up of 31.5 months, recurrence and death occurred in 17 (18.9%) and 5 (5.6%) cases, respectively. Among the pooled cases, the 5-year PFS and OS were 69.6% and 89.2%, respectively. A multivariate model demonstrated that partial resection (HR 4.792, 95% CI 2.909–7.893, p < 0.001) and no radiotherapy (HR 0.165, 95% CI 0.065–0.423, p < 0.001) were independent adverse factors for poor PFS.
GTR and radiotherapy were independent favorable factors for PFS of intracranial GCTs. Based on these findings, GTR alone or GTR plus radiotherapy was advocated as an optimal treatment; otherwise, partial resection plus radiotherapy with a dose ≥ 45 Gy, if tolerable, was a secondary alternative. Lack of randomized data of the study was stressed, and future studies with larger cohorts are necessary to verify these findings.
Systematic review no.: CRD42018090878 (crd.york.ac.uk/PROSPERO/)
Jie Zhang, Dong-Xiao Zhuang, Cheng-Jun Yao, Ching-Po Lin, Tian-Liang Wang, Zhi-Yong Qin and Jin-Song Wu
The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection.
Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection.
Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up.
This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.
Tao Yu, Xingwen Sun, Yan You, Jie Chen, Jun-mei Wang, Shuo Wang, Ning Lin, Buqing Liang and Jizong Zhao
Brain capillary telangiectasias (BCTs) are usually small and benign with a predilection in the pons and basal ganglion. Reports of large and symptomatic BCTs are rare. Large BCTs have a much higher risk of causing uncontrolled bleeding and severe neurological defects, and they can be fatal if left untreated. Therefore, large BCTs should be managed with special caution. Because of the lack of reports, diagnosis of large BCTs has been difficult. Strategies of management are undefined for large or giant BCTs.
The current study presents 5 cases of giant and large BCTs. To the authors’ knowledge, this is the largest series of this disease ever reported. Radiological findings, histopathological characteristics, clinical presentations, and surgical management were analyzed in 5 symptomatic, unusually large BCTs (mean diameter 5.06 cm, range 1.8–8 cm).
Four patients presented with focal or generalized seizures, and 1 patient presented with transient vision loss attributed to the lesions. Gross-total resection of the lesion was achieved in all patients. After surgery, the 4 patients with seizures were symptom free for follow-up periods varying from more than 1 to 5 years with no additional neurological deficits.
The unique location, radiological characteristics, and clinical course suggest that giant BCTs could be a different entity from small BCTs. Surgery might be a good option for treatment of patients with intractable neurological symptoms, especially in those with surgically accessible locations. Complete removal would be anticipated to provide relief of the symptoms without causing new neurological deficits.
Da Li, Yu-Ming Jiao, Liang Wang, Fu-Xin Lin, Jun Wu, Xian-Zeng Tong, Shuo Wang and Yong Cao
Surgical management of brainstem lesions is challenging due to the highly compact, eloquent anatomy of the brainstem. This study aimed to evaluate the safety and efficacy of preoperative diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in brainstem cavernous malformations (CMs).
A prospective randomized controlled clinical trial was performed by using stratified blocked randomization. The primary eligibility criterion of the study was being a surgical candidate for brainstem CMs (with informed consent). The study enrolled 23 patients who underwent preoperative DTI/DTT and 24 patients who did not (the control group). The pre- and postoperative muscle strength of both limbs and modified Rankin Scale (mRS) scores were evaluated. Muscle strength of any limb at 12 months after surgery at the clinic visit was the primary outcome; worsened muscle strength was considered to be a poor outcome. Outcome assessors were blinded to patient management. This study reports the preliminary results of the interim analysis.
The cohort included 47 patients (22 women) with a mean age of 35.7 years. The clinical baselines between these 2 groups were not significantly different. In the DTI/DTT group, the corticospinal tract was affected in 17 patients (73.9%): it was displaced, deformed/partially interrupted, or completely interrupted in 6, 7, and 4 patients, respectively. The surgical approach and brainstem entry point were adjusted in 3 patients (13.0%) based on DTI/DTT data. The surgical morbidity of the DTI/DTT group (7/23, 30.4%) was significantly lower than that of the control group (19/24, 79.2%, p = 0.001). At 12 months, the mean mRS score (1.1, p = 0.034) and percentage of patients with worsened motor deficits (4.3%, p = 0.006) were significantly lower in the DTI/DTT group than in the control group (1.7% and 37.5%). Multivariate logistic regression identified the absence of preoperative DTI/DTT (OR 0.06, 95% CI 0.01–0.73, p = 0.028) and use of the 2-point method (OR 4.15, 95% CI 1.38–12.49, p = 0.011) as independent adverse factors for a worsened motor deficit. The multivariate model found a significant correlation between poor mRS score and both an increased preoperative mRS score (t = 3.559, p = 0.001) and absence of preoperative DTI/DTT (t = −2.747, p = 0.009).
DTI/DTT noninvasively allowed for visualization of the anatomical relationship between vital tracts and pathologies as well as facilitated the brainstem surgical approach and entry-point decision making. The technique was valuable for complex neurosurgical planning to reduce morbidity. Nonetheless, DTI/DTT data should be interpreted cautiously.
■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized controlled trial; evidence: class I.
Clinical trial registration no.: NCT01758211 (ClinicalTrials.gov)