Guijun Jia

Clinical course of untreated pediatric brainstem cavernous malformations: hemorrhage risk and functional recovery

OBJECT The aim of this study was to investigate the clinical appearance of untreated pediatric brainstem cavernous malformations (CMs) and to identify the hemorrhage risks and functional outcomes. METHODS All pediatric patients with a diagnosis of brainstem CM between 1985 and 2012 were registered. The clinical chart and radiographs were recorded, and follow-up evaluations were obtained prospectively. RESULTS A total of 85 patients (69.4% male) were included with a mean age of 12.7 years. Sixty-seven patients (78.8%) had prior hemorrhage, and 6 patients (7.1%) were asymptomatic. There were 15 midbrain lesions, 53 pons lesions, and 17 medulla lesions. The mean lesion size was 1.9 cm. During a total of 401.6 patient-years of follow-up, 47 hemorrhages occurred in 37 patients, and the annual hemorrhage rate was 11.7% per patient-year. The mean hemorrhage interval was 47.8 months. The hemorrhage risk declined over time, especially after the first 2 years. Both a lesion size ≥ 2 cm (hazard ratio [HR] 2.122, p = 0.037) and the presence of perilesional edema (HR 2.192, p = 0.039) predicted future hemorrhage and were associated with a high annual hemorrhage rate. The hemorrhage-free survival at 6 months was 85.7%, and at 1, 5, 10, and 15 years was 71.5%, 49.4%, 27.5%, and 13.7%, respectively. At the most recent functional evaluation, 33 patients (38.8%) had improved, 32 (37.6%) had stabilized, and 20 (23.5%) had worsened, without any deaths. Twenty-two patients (25.9%) obtained a full recovery. Prospective hemorrhage (HR 0.191, p = 0.003) was the adverse predictor for full recovery. Full recovery primarily occurred within the first 12 months, after which the chance of full recovery decreased. The cumulative percentage of complete recovery at 6 months was 32.7%, and at 1, 3, and 5 years was 40.8%, 43.6%, and 49.2%, respectively. CONCLUSIONS In this study the hemorrhage rate was relatively high in pediatric brainstem CMs, although the functional outcome was acceptable. The decline in hemorrhage risk and the identified adverse predictors in this study were helpful for clinicians and patients when deciding on treatment. Referral bias and the insufficient follow-up period of the study were highlighted as limitations.

Treatment Response and Prognosis After Recurrence of Atypical Meningiomas

OBJECTIVE Intracranial atypical meningiomas have a greater rate of recurrence than benign meningiomas. Scant literature, however, is available regarding the treatment and prognosis of these tumors after recurrence. The objective of this study was to analyze the treatment outcomes and prognostic factors of atypical meningiomas after recurrence of disease. METHODS Forty-one cases with clinical characteristics and follow-up data were available in our department from 2000 to 2013. Certain factors, such as sex, age, preoperative Karnofsky Performance Status Scale score, location, prerecurrence tumor precursor, interval time, Simpson grade, histologic grade after recurrence, and radiotherapy, were selected to study the relationship with the prognosis of the tumors. RESULTS The mean progression-free survival (PFS) and overall survival (OS) in our cases were 40.5 ± 4.7 and 57.1 ± 5.8 months, respectively. The 1-, 3-, and 5-year PFS rates were 79.8%, 44.1%, and 39.2%, respectively, and the corresponding OS rates were 92.4%, 66.1%, and 48.8%, respectively. The precursors of recurrent tumors were transformed meningiomas, an interval time less than 24 months, and a postrecurrence histologic diagnosis of anaplastic meningioma might predict an unfavorable outcome. Surgery Simpson I and II can improve the PFS and OS of tumors. Because of the limited number of cases, we could not identify a relationship between radiotherapy and prognosis. CONCLUSIONS Recurrent atypical meningiomas are intractable tumors with a high rate of recurrence and death. Total resection of the tumors under relatively safe conditions remains the most suitable treatment strategy.

Surgical management of pediatric brainstem cavernous malformations

OBJECT The goal of this study was to evaluate surgical outcomes of pediatric brainstem cavernous malformations (CMs) and identify the risk factors associated with postoperative full recovery and rebleeding. METHODS The clinical charts and radiographs from a series of 52 pediatric patients (37 male and 15 female; mean age 12.2 years; range 1-17 years) who underwent surgery for brainstem CMs between 1996 and 2011 were reviewed. Follow-up evaluation measures were obtained retrospectively. Neurological function was evaluated using the modified Rankin Scale (mRS) score. RESULTS The lesion locations among the 52 patients included the midbrain (n = 7, 13.5%), pons (n = 38, 73.1%), and medulla (n = 7, 13.5%). The mean duration of symptoms was 18.5 months, and the preoperative annual hemorrhage and rebleeding rates were 12.3% and 32.5% per patient-year, respectively. The mean lesion size was 2.1 cm. Gross-total resection without surgery-related death was achieved in 49 patients (94.2%). Immediate postoperative reduced neurological function was observed in 17 patients (32.7%). Surgical morbidities developed in 25 patients (48.1%) and remained in 11 patients (21.2%) after 7.9 years of follow-up. The mean mRS scores at admission, discharge after surgery, 3 and 6 months postsurgery, and recent evaluation were 2.0, 2.3, 2.0, 1.5, and 1.0, respectively. The postoperative mRS scores at 6 months (p < 0.001) and on recent evaluation (p < 0.001) were significantly lower than those at admission. Postoperative rebleeding occurred in 2 patients, and the postoperative annual rebleeding rate was 0.5% per patient-year. By the most recent evaluation, 10 patients (19.2%) had achieved full recovery and all patients were either improved (n = 32, 61.5%) or unchanged (n = 20, 38.5%). The adverse predictors for full recovery included age ≥ 12 years (HR 0.230, p = 0.021), ≥ 2 preoperative hemorrhages (HR 0.124, p = 0.048), and poor preoperative status (HR 0.197, p = 0.040). An HR < 1 predicted poor complete recoveries. The single risk factor predicting postoperative rebleeding was incomplete resection (χ2 = 4.340, p = 0.037). CONCLUSIONS Fair outcomes for pediatric brainstem CMs could be obtained through surgery, but only a few patients achieved full recovery. Thus, to minimize surgical morbidity, surgical planning must be tailored to individual patients in all cases in which an operation is warranted. Complete resection must be attempted to reduce the risk of postoperative rebleeding. The predictors associated with complete postoperative recovery were referential for determining treatment.

Factors for tumor progression in patients with skull base chordoma.

Skull base chordoma is a rare and fatal disease, recurrence of which is inevitable, albeit variable. We aimed to investigate the clinicopathologic features of disease progression, identify prognostic factors, and construct a nomogram for predicting progression in individual patients. Data of 229 patients with skull base chordoma treated by one institution between 2005 and 2014 were retrieved and grouped as primary and recurrent. Kaplan–Meier survival of progression was estimated, taking competing risks into account. Multivariable Cox regression was used to investigate survival predictors. The primary group consisted by 183 cases, gained more benefits on 5‐year progression‐free survival (PFS) (51%) and mean PFS time (66.9 months) than the recurrent group (46 cases), in which 5‐year postrecurrent PFS was 14%, and mean postrecurrent PFS time was 29.5 months. In the primary group, visual deficits, pathological subtypes, extent of bone invasion, preoperative Karnofsky performance scale (KPS) score, and variation in perioperative KPS were identified as independent predictors of PFS. A nomogram to predict 3‐year and 5‐year PFS consisted of these factors, was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.68). In the recurrent group, marginal resection (P = 0.018) and adjuvant radiotherapy (P = 0.043) were verified as protective factors associated with postrecurrent PFS. Factors for tumor progression demonstrated some differences between primary and recurrent cases. The nomogram appears useful for risk stratification of tumor progression in primary cases. Further studies will be necessary to identify the rapid‐growth histopathological subtype as an independent predictor of rapid progression.

How to Address Small- and Medium-Sized Acoustic Neuromas with Hearing: A Systematic Review and Decision Analysis

OBJECTIVE Small- and medium-sized acoustic neuromas (ANs) increase in both number and proportion. Observation, radiosurgery, and microsurgery are all used to treat this disease; however, the appropriate treatment is controversial, especially in patients with hearing. METHODS We searched the MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Con-trolled Trials), LILACS (Latin American and Caribbean Center on Health Sciences Information), and CMB (Chinese Biomedical Database) databases without limits on the language and the time of publication. For the wait-and-scan strategy, we included the population-based prospective studies with sufficient follow-up time and information. We also attempted to locate high-level evidence that compared radiosurgery with microsurgery. The data were extracted from the studies to synthesize the probabilities. We surveyed 60 patients with small- and medium-sized ANs to plot the outcomes on a linear scale to measure the utility. RESULTS Eight studies met the inclusion criteria of the wait-and-scan strategy, and 3 grade II evidence studies were found that compared microsurgery with radiosurgery. After synthesizing the data in 3 groups, the preservation of useful hearing was 58.9%, 60.2%, and 4.3%, whereas the rate of tumor control was 71.1%, 97.0%, and 94.3%, respectively. The expected value for radiosurgery was 0.68, whereas the expected values for wait-and-scan and surgery were 0.64 and 0.28, respectively. CONCLUSION On the basis of the evidence, radiosurgery is the optimal choice for small- and medium-sized ANs. Because of the current difficulty with understanding the natural history of ANs, we suggest that there is a need for new evidence and a health economics assessment to update this result.

The Brachyury Gly177Asp SNP Is not Associated with a Risk of Skull Base Chordoma in the Chinese Population

A recent chordoma cancer genotyping study reveals that the rs2305089, a single nucleotide polymorphism (SNP) located in brachyury gene and a key gene in the development of notochord, is significantly associated with chordoma risk. The brachyury gene is believed to be one of the key genes involved in the pathogenesis of chordoma, a rare primary bone tumor originating along the spinal column or at the base of the skull. The association between the brachyury Gly177Asp single nucleotide polymorphism (SNP) and the risk of skull base chordoma in Chinese populations is currently unknown. We investigated the genotype distribution of this SNP in 65 skull-base chordoma cases and 120 healthy subjects. Comparisons of the genotype distributions and allele frequencies did not reveal any significant difference between the groups. Our data suggest that the brachyury Gly177Asp SNP is not involved in the risks of skull-base chordoma, at least in the Chinese population.

Clinical features and surgical outcomes of patients with skull base chordoma: a retrospective analysis of 238 patients

OBJECTIVE Skull base chordoma is relatively rare, and a limited number of reports have been published regarding its clinical features. Moreover, the factors associated with extent of resection, as well as the value of marginal resection for long-term survival, are still in question for this disease. The objective of this study was to investigate these factors by evaluating their clinical features and surgical outcomes. METHODS A retrospective analysis of 238 patients with skull base chordomas, who met the inclusion criteria, was performed. This study summarized the clinical features, selection of approaches, degree of resection, and postoperative complications by statistical description analyses; proposed modified classifications of tumor location and bone invasion; studied the contributions of the clinical and radiological factors to the extent of resection by Pearson χ2, ANOVA, rank test, and binary logistic regression analysis; and estimated the differences in overall survival and progression-free survival rates with respect to therapeutic history, classification of tumor location, extent of bone invasion, and extent of tumor resection by the Kaplan-Meier method. A p value < 0.05 was considered statistically significant. RESULTS The study included 140 male and 98 female patients with a mean age of 38.1 years. Headache and neck pain (33.2%) and diplopia (29%) were the most common initial symptoms. Sphenoclival type accounted for the largest proportion of tumor location (59.2%); endophytic chordoma was the more common type of bone invasion (81.5%). Lateral open approaches were performed in two-thirds of the study population (78.6%). The rate of marginal resection was 66%, composed of gross-total resection (11.8%) and near-total resection (54.2%). Meningitis (8%) and CSF leakage (3.8%) were the most frequent complications. The mean follow-up period was 43.7 months. The overall survival and progression-free survival rates at 5 years were 76% and 45%, respectively. Recurrent tumor and larger tumor volume (≥ 40 cm3) were identified as risk factors of marginal resection. Patients who presented with recurrent tumor and underwent intralesional resection had a worse long-term outcome. CONCLUSIONS The classifications of both tumor location and bone invasion demonstrated clinical value. Marginal resection was more likely to be achieved for primary lesions with smaller volumes (< 40 cm3). The rate of CSF leakage declined due to improved dura mater repair with free fat grafts. Marginal resection, or gross-total resection when possible, should be performed in patients with primary chordomas to achieve better long-term survival.

Less-aggressive surgical management and long-term outcomes of jugular foramen paragangliomas: a neurosurgical perspective.

OBJECTIVE The aim of this study was to analyze the neurological functional outcome and recurrent risks in surgically treated jugular foramen paragangliomas (JFPs) and to propose an individualized therapeutic strategy. METHODS Clinical charts and radiological information were reviewed retrospectively in 51 consecutive cases of JFPs. Less-aggressive surgical interventions were adopted with the goal of preserving neurovascular structures. Scheduled follow-up was performed. RESULTS The mean age of the patients in the cases reviewed was 41.6 years, and the group included 27 females (52.9%). The mean preoperative Karnofsky Performance Scale (KPS) score was 78.4. The mean lesion size was 3.8 cm. Forty-three cases (84.3%) were Fisch Type D, including 37 cases (72.5%) of Type Di1 and Di2. Thirty-seven cases (72.5%) were Glasscock-Jackson Type III-IV. Gross-total resection and subtotal resection were achieved in 26 (51.0%) and 22 (43.1%) cases, respectively. Surgical morbidities occurred in 23 patients (45.1%), without surgery-related mortality after the first operation. The mean postoperative KPS scores at discharge, 3 months, 1 year, and most recent evaluation were 71.8, 77.2, 83.2, and 79.6, respectively. The mean follow-up duration was 85.7 months. The tumor recurrence/regrowth (R/R) rate was 11.8%. Compared with preoperative status, swallowing function improved or stabilized in 96.1% and facial function improved or stabilized in 94.1% of patients. A House-Brackmann scale Grade I/II was achieved in 43 patients (84.3%). Overall neurological status improved or stabilized in 90.0% of patients. Pathological mitosis (HR 10.640, p = 0.009) was the most significant risk for tumor R/R. A 1-year increase in age (OR 1.115, p = 0.037) and preoperative KPS score < 80 (OR 11.071, p = 0.018) indicated a risk for recent poor neurological function (KPS < 80). Overall R/R-free survival, symptom progression-free survival, and overall survival at 15 years were 78.9%, 86.8%, and 80.6%, respectively. CONCLUSIONS Surgical outcomes for JFPs were acceptable using a less-aggressive surgical strategy. Most patients could adapt to surgical morbidities and carry out normal life activities. Preserving neurological function was a priority, and maximal decompression with or without radiotherapy was desirable to preserve a patients quality of life when radical resection was not warranted. Early surgery plus preoperative devascularization was proposed, and radiotherapy was mandatory for lesions with pathological mitosis.

Brachyury: A sensitive marker, but not a prognostic factor, for skull base chordomas

Patients with skull base chordomas have a poor prognosis, and the role of the protein expression of brachyury in chordomas remains to be fully elucidated. The present study used immunohistochemistry to analyze 57 cases of skull base chordoma, and analyzed the clinical data of the patients. The results demonstrated that the protein expression of brachyury was negative in 8.8% (5/57) of the cases. The weak/positive, positive and strong/positive rates were 5.3% (3/5 7), 21.1% (12/57) and 64.9% (37/57), respectively. The association between the expression of brachyury and recurrence was not statistically significant. Kaplan-Meier analysis revealed that the degree of surgery, rather than the expression of brachyury, was associated with tumor recurrence (P=0.001). In conclusion, the results of the present study demonstrated that the expression of Brachyury offers a sensitive marker, but not a risk factor, for skull base chordomas, and radical surgery is recommended.

Growth hormone secreting pituitary microadenomas and empty sella – An under-recognized association?

OBJECTIVE To describe an association of growth hormone (GH) secreting pituitary microadenomas and empty sella (ES), which has been described in case reports - the underlying mechanisms are unclear. METHODS We retrospectively analyzed patients operated for GH-producing pituitary adenomas between February 2004 and February 2009. Magnetic resonance imaging (MRI), computed tomography (CT) imaging, and pituitary function testing were performed. All cases underwent transsphenoidal surgery (TSS). Mean follow up was 38 months (range 12-80 months). RESULTS Out of 152 patients with acromegaly due to GH-producing pituitary adenomas (female:male=73:79; age range 17-63 years), 69 patients had microadenomas (45.4%; 38 females, 31 males). We found 14 cases (14/69, 20.3%), all microadenomas, with presurgical evidence of ES - 10 females (71%) and 4 males (29%) (female:male=2.5:1). When compared with 103 patients with GH-negative microadenomas treated in the same time period (ES in 4 of 103; 3.9%), ES was highly significantly associated with GH production by the microadenoma (p=0.001). In acromegalics with empty sella, no cases of ectopic adenoma were found. Postoperatively, GH and IGF-1 levels fell in all patients, and 7 cases had random GH and IGF-1 levels consistent with cure. CONCLUSION The combination of GH-producing microadenomas and empty, enlarged sella is not rare. In this setting, preoperative CT scans are very useful and the transsphenoidal approach is efficient and safe. The mechanism underlying the association of GH-producing microadenomas and empty sella remains unclear and requires further studies.