Volume 36 · Issue 09 · 2020

To explore the clinical features and treatment strategy of pediatric tectal gliomas (TGs).

The clinical data of patients with the diagnosis of TGs (age ≤ 18 years old) admitted to Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University from January 1996 to December 2019 were retrospectively analyzed. Eighty-four patients first underwent treatment of hydrocephalus. Among them, 42 patients underwent ventriculoperitoneal shunt (VPs) and 42 underwent endoscopic third ventriculostomy (ETV). A total of 24 patients eventually underwent tumor resection by transcallosal interforniceal/transchoroidal approach (n=11), supracerebellar infratentorial/trans-fourth ventricular approach (n=10) and sub-occipital transtentorial approach (n=3). According to MRI at follow-up, the recovery of hydrocephalus, tumor resection and progression were evaluated.

Of the 88 patients, the median age was 9.3 years (range: 6 months to 18 years). The obstructive hydrocephalus with intracranial hypertension due to tumor compression was the primary presentation at diagnosis and reported in 45 patients (51.1%). Of 42 cases with failure of VPs, 14 (33.3%) received additional revisions. Only 6 out of 42 cases (14.3%) in the ETV group required additional VPs and the successful rate of ETV was 85.7% (36/42). Synchronous tissue biopsy during ETV was performed in 9 patients. Among the 24 cases(27 procedures) who underwent craniotomy, total resection was achieved in 7 procedures, near total resection 14, and partial resection in 6. After hydrocephalus treatment, 58 cases were followed up without undergoing craniotomy or biopsy and histological examination was conducted in the remaining 30 cases. Among them, 25 patients had low grade glioma, 3 patients had high grade gliomas, and gliosis was reported in 2. The median follow-up duration of 88 children was 39.5 months (4-288 months). Among the 76 children who did not undergo early craniotomy, the follow-up indicated tumor progression in 24 patients (31.6%), 2 patients (8.3%) underwent a second resection due to tumor recurrence and 2 (2.3%) deaths were documented. The remaining 86 cases kept a normal life. There were 4 cases of transient memory impairment, 3 cases of eye movement disorder and 20 cases of recurrence of hydrocephalus.

Pediatric TGs are generally low-grade gliomas and obstructive hydrocephalus is its mainly manifestation. ETV should be the first choice and an alternative to shunt placement for hydrocephalus treatment. Resection surgery is required in only some cases. In most cases, general recommendation for treatment is close observation after management of hydrocephalus, while attention should be paid to the tumor progression.

To investigate the clinical features and prognostic factors of central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT).

Thirty-one AT/RT patients diagnosed by postoperative pathological examination and surgically treated at Department of Neurosurgery, West China Hospital, Sichuan University from January 2007 to August 2019 were retrospectively analyzed. Kaplan-Meier method was used to analyze the postoperative survival of the children.

Among the 31 children, 17 were males and 14 were females. The median age of onset was 22 months (2 months to 15 years). There were 21 cases in the ≤3-year-old group and 10 cases in the >3-year-old group. Of the 31 patients, 17 were in the supratentorial region, 13 in the infratentorial region, and 1 across the supratentorial and infratentorial regions. The maximum diameter of the tumor was 2.5-9.1 (5.2±1.7) cm. Twenty-five patients had total tumor resection and 6 had subtotal resection. Compared with the > 3-year-old group, the proportion of men in the≤3-year-old group was slightly higher (3/10 vs. 14/21), and the proportion of tumors located in the supratentorial region was slightly lower (8/10 vs. 9/21), and the rate of peritumoral edema was slightly lower (4/9 vs. 2/20), while the differences were not statistically significant (all P>0.05). Followed up for 1 to 60 months, the median survival time was 5 (1-60) months. The 1-year survival rate was 16.1% (5/31) and the 2-year survival rate was 3.2% (1/31). Kaplan-Meier analysis showed that the median survival time in the ≤3-year-old group was 4.0 (1.0, 6.5) months, and that in the >3-year-old group was 9.5 (6.0, 21.0) months. The difference was statistically significant (P=0.002). The median survival time of 9 children with adjuvant radiotherapy and/or chemotherapy was 7.0 (4, 18.5) months, and the median survival time of 22 children who underwent surgery only was 4.0 months (1.0, 7.0), the difference was statistically significant (P=0.037).

The overall prognosis of AT/RT seems poor. In addition, the proportion of young children ≤3 years old is relatively higher and their survival time seems shorter.Adjuvant radiotherapy and/or chemotherapy may help prolong the survival of children.

To investigate the prognosis of surgical treatment for fourth ventricle ependymomas in children.

The clinical data of 17 children with fourth ventricle ependymomas who underwent surgical treatment at Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University from January 2008 to October 2019 were retrospectively reviewed. The male/female ratio was 11/6. The median diagnostic age was 5 (1-16) years old. There were 11 cases of >3 years old, 9 cases of ≤5 years old and 6 cases of ≤3 years old. The patients older than 3 years underwent radiotherapy and chemotherapy according to the individual conditions. All the children underwent clinical follow-up.Kaplan-Meier method was used to analyze the survival of patients.

Of all 17 patients, total resection was achieved in 11 cases and subtotal resection in 6 cases. Postoperative pathological examination of all patients showed that there were 8 cases of WHO grade Ⅱ ependymoma, and 9 cases of WHO grade Ⅲ (anaplastic) ependymoma. The median follow-up time was 16 (1-96) months. By the last follow-up, 10 patients died, 7 survived and 3 relapsed. The Kaplan Meier analysis showed that the 1-year overall survival rate of 17 patients was 58.8%, 2-year survival rate was 43.4%, and the median survival time was 18.0 months. There was no significant difference in survival time according to sex, age, tumor resection degree and WHO classification (all P > 0.05). The survival probability of patients with Ki-67 index < 20% was higher than that of patients with Ki-67 index ≥20% ( P=0.030).

The prognosis of children with fourth ventricle ependymomas seems poor. The Ki-67 index may be an important factor affecting the survival of children and other factors need to be further studied in a larger cohort.

To investigate the therapeutic strategies and prognosis of intracranial immature teratomas with negative serum tumor markers including alpha fetoprotein (AFP) and beta human chorionic gonadotropin (β-hCG).

We retrospectively analyzed the clinical data of 23 intracranial immature teratoma patients with negative preoperative serum tumor markers (AFP and β-hCG) who were admitted to Department of Neurosurgery, Huashan Hospital, Fudan University from January 1997 to December 2019. All patients underwent surgery to remove the tumor. Among them, postoperative radiotherapy (merely conventional radiotherapy in 10, conventional radiotherapy combined with gamma knife therapy in 7, and merely gamma knife therapy in 1) was performed in 18 patients and chemotherapy in 10. Kaplan-Meier method and log-rank test were used for survival analysis and comparison.

Of the 23 patients, 16 underwent total resection, 4 had subtotal resection, and 3 had partial resection. Postoperative pathological results indicated 19 cases of immature teratoma and 4 cases of mixed germ cell tumor containing immature teratoma components. Of the 23 patients, 2 were lost to follow-up and 21 were followed up. The 5-year and 10-year survival rates of 23 patients were 71.7% and 65.7%, respectively. Lag-rank analysis results showed that postoperative radiotherapy and chemotherapy were not influencing factors for the survival rate of patients (both P>0.05). Among the 16 patients with residual tumors or recurrent tumors after surgery, the 5-year survival rates of those undergoing gamma knife treatment (8 cases) and those without gamma knife treatment (8 cases) were 100.0% and 28.6% respectively (P=0.01).

As for intracranial immature teratoma with negative preoperative serum tumor markers, surgical treatment should be preferred and total resection should be achieved as far as possible. Timely treatment using Gamma knife could be an effective complementary therapy for postoperative residual or recurrent tumor, which could lead to a relatively long survival.

To investigate the clinical features of cerebellar mutism syndrome (CMS) and its related preoperative risk factors of CMS in children post surgery of posterior fossa tumor.

The clinical data of 122 children with posterior fossa tumors admitted to Department of Neurosurgery, Beijing Children′s Hospital, Capital Medical University from January 2015 to December 2018 were retrospectively analyzed. They were divided into CMS group (n=31) and non-CMS group (n=91) according to whether CMS is present. The clinical characteristics of CMS were observed, and the clinical features and preoperative imaging features were compared between the two groups. Multivariate logistic regression analysis was used to determine the preoperative risk factors associated with postoperative CMS.

Among all 122 cases, 31 (25.4%) developed CMS after operation. Mutism occurred immediately after operation in 19 cases, less than 3 days after operation in 11 cases, and in 1 case on the 7th day after operation. At the last follow-up, except for 3 deaths, the mutism duration in the other 28 cases was 7-315 days. The CMS lasted for 7-28 days in 12 cases and less than 90 days in 25 cases. Compared with non-CMS group, the proportion of males in the CMS group was higher [80.6% (25/31) vs. 49.5% (45/91)], and the proportion of medulloblastoma patients was higher [71.0% (22/31) vs. 37.4% (34/91)], and the difference was statistically significant (both P<0.05). Compared with non-CMS group, the proportion of solid tumors in the CMS group was higher [92.9%(26/28)vs. 67.5%(56/83)], the lower vermis was more involved [100.0%(28/28) vs. 69.9%(58/83)], and the proportion of brainstem compression was higher [85.7%(24/28) vs. 61.4%(51/83)]. Those difference were all significant (all P<0.05). There was significant difference in the tumor location between the two groups (P<0.05). There was no significant difference in age, tumor size, Evan′s index, hydrocephalus, paraventricular edema or the proportion of upper vermis involvement between the two groups(allP>0.05). Multivariate logistic regression analysis showed that male (OR=4.7, 95%CI: 1.5-14.1, P=0.006) and brain stem compression (OR=4.7, 95%CI: 1.3-16.4, P=0.017) were independent risk factors for postoperative CMS in children with posterior fossa tumors.

CMS mostly occurs in the early stage after operation and recovers within 3 months. Male and brainstem compression may be the independent risk factors of postoperative CMS.

To explore a convenient and effective way of external drainage for infants and young children with acute hydrocephalus.

A retrospective analysis was conducted on 43 children of acute hydrocephalus who underwent external drainage of the lateral ventricle at Department of Neurosurgery, Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine. All children demonstrated significant symptom of intracranial hypertension (IH) during infection or bleeding. Intermittent flow control mode was employed for external drainage, which was performed when the child was quiet or asleep. The total daily drainage was controlled at about 100 ml. The efficacy of external drainage and the incidence of related bleeding, cerebrospinal fluid (CSF) leakage and infection were observed.

A total of 47 procedures of ventricular puncture and external drainage were performed in 43 cases. All children with IH symptoms were significantly improved, and their infection or bleeding were resolved. The median duration of the catheter maintenance was 14 (5 to 60) d. During external drainage, there were 2 cases of secondary ventricular hemorrhage (4.7%), 3 cases of CSF leakage (7.0%), 2 cases of catheter blockage (4.7%), and none of them had catheter-related secondary infection. The second-stage ventricular-peritoneal shunting was performed in all cases.

External drainage with intermittent flow control mode during the period of intracranial infection period or ventricular hemorrhage in infants and young children with acute hydrocephalus can safely and effectively reduce intracranial pressure, reduce the risk of cerebral hemorrhage and subdural fluid accumulation, and does not seem to increase the risk of secondary infection.

To investigate therapeutic effects of postoperative fluid and electrolyte management based on enhanced recovery after surgery (ERAS) in craniopharyngioma patients.

A total of 80 patients with craniopharyngiomas undergoing surgical operation at Department of Neurosurgery, Xijing Hospital, Air Force Military Medical University from January 2018 to March 2020 were retrospectively enrolled in this study. Among them, 37 patients in group A received normal fluid and electrolyte strategies, while 43 patients in group B were treated with ERAS based managements post operation. The clinical features, serum Na⁺ level and fluctuations, diabetes insipidus control quality, and therapeutic effect in the two groups were evaluated after surgery.

There was no statistical difference in age, gender, body mass index, tumor maximal diameter, tumor texture, QST type, surgical approach, extent of tumor resection, or pathological type between group A and group B (all P>0.05). In the first week after surgery, the serum Na⁺ values in group B appeared less frequently at high-risk levels (<130 mmol/L and >150 mmol/L) than those in group A [median (interquartile range): 53 (20.3)vs. 84 (3.5), 67 (25.6) vs. 90 (35.8), both P<0.05], while they were more often at low-risk level (130-150 mmol/L) in group B than in group A [141 (54.1)vs. 77 (30.7), P<0.05]. From day 1 to day 7 post surgery, daily fluctuation ranges of serum Na⁺ in group B were lower compared with those in group A (all P<0.05), and the fluctuation ranges in both groups were gradually reduced with the increase of postoperative time (F₁=105.200, F₂=87.100, both P<0.05). The difference in the average urine output between group A and B had no statistical significance at day 1 post surgery (P>0.05). However, daily urine output in group A was higher than that in group B from day 2 to day 7 post surgery (allP<0.05). Furthermore, the average daily urine output in both groups presented a trend of decrease from day 2 to day 7 post surgery (F₁=62.600, F₂=99.400, both P<0.05). Glasgow coma scale (14.5±3.6 pointsvs. 10.3±4.9 points) and postoperative length of stay (9.7±2.9 d vs. 14.9±4.8 d) in group B were superior to those in group A (both P<0.05). There was no statistical difference in Karnofsky performance status and hospital anxiety and depression scale between the two groups (allP>0.05).

ERAS based management of fluid and electrolyte could stabilize serum Na⁺ level, reduce serum Na⁺ fluctuation range, control diabetes insipidus and improve therapeutic effect in craniopharyngioma patients.

To explore the clinical characteristics, diagnosis and treatment of spinal cord injury without radiological abnormality (SCIWORA) in children.

A retrospective analysis was performed involving 32 children with SCIWORA who were admitted to Neurosurgery Department of Children′s Hospital of Chongqing Medical University from April 2010 to November 2019. All patients underwent conservative treatment including bed rest, local immobilization, hormone, mannitol, nerve growth factor, et al. and catheterization for urinary retention. All the children underwent clinical follow-up post discharge, and Frankel grading was used to assess the recovery of spinal cord injury.

Among 32 patients, the ratio of boy to girl was 1.0 ∶2.2. The median age was 82 months (range: 2 months to 180 months). All cases had a clear traumatic history, and the most common injury cause was back bend movements in dance (19/32), followed by traffic accidents (6/32), fall from heights (3/32) and fall down on ground (3/32) and injury by heavy objects (1/32). The main clinical manifestations included weakness in both legs (23/32), weakness with numbness in both legs (8/32) and numbness in both legs (1/32). Symptoms usually appeared immediately after injury (23/32) and progressively aggravated (31/32). CT and X-ray examination of the spine showed no abnormalities, while MRI examination showed more abnormalities (26/32) presenting with spinal cord contusion (23/32) and spinal cord hemorrhage (3/32). The lesion was involving the thoracic segments in 20 cases, cervical segments in 4, cervical, thoracic and lumbar segments in 2, cervical and thoracic segments in 4, and thoracic and lumbar segments in 2 cases. After one week of treatment, the Frankel grade of 32 children was significantly higher than that before treatment (P < 0.05). The Frankel grade improved by 4 in 6 cases, 3 in 2, 2 in 5, and 1 in 7. During treatment, 9 cases (28.1%) developed urinary tract infection. The median follow-up time of all 32 patients was 21 months (3 months to 5 years). During the follow-up, 26 patients received regular rehabilitation treatment, and 6 (grade E) received no special treatment. At the last follow-up, Frankel grading was significantly higher than that before treatment ( P < 0.05), while it was not statistically different from that at 1 week post treatment ( P > 0.05).

SCIWORA in children seems more common in girls, and back bend movements in dance is the most common cause. Thoracic spinal cord is involved in most cases. Total spinal MRI examination is the optimal method to make the diagnosis of SCIWORA and conservative treatment is the main therapy. To avoid delaying treatment, patients with the clear history of related trauma and symptoms should receive the spinal MRI immediately.

To summarize the clinical efficacy of early endoscopy-assisted craniectomy and postoperative cranial orthosis therapy for infants with nonsyndromic craniosynostosis.

A retrospective analysis was conducted on the clinical data of 8 children with non-syndromic craniosynostosis who were admitted to Department of Neurosurgery, Beijing Children′s Hospital, Capital Medical University from July 2018 to July 2019. The children were 4.1±0.8 months (3 to 5 months) old, and among them there were 5 cases of sagittal synostosis, 2 cases of coronal craniosynostosis, and 1 case of multiple craniosynostosis. All 8 children underwent endoscopy-assisted craniectomy. After operation, the children underwent the therapy with orthopedic helmets for 9 to 12 months and ≥22 h per day. Regular clinical follow-up was conducted after wearing an orthopedic helmet to scan the skull for establishing a 3D model, reviewing cerebral morphology and measuring head circumference, head transverse diameter, head anteroposterior diameter, cephalic index (CI), cranial vault asymmetry index (CVAI), vertex-nasion-gnathion (V-N-G) included angle, while taking photos of the head and face of preoperative and postoperative conditions to evaluate the correction effect. The infants with abnormal growth quotient before the surgery were reviewed after the surgery to assess the improvement of neurological development by the treatment.

Among the 8 cases, 2 adopted coronal suture strip resection, 5 had sagittal suture strip resection, and 1 had multiple cranial suture strip resection. No serious complications occurred after operation. The follow-up time of the 8 patients was 7.5±1.5 months (6-10 months). At 6 months post operation, the CVAI of the two children with unilateral coronal suture synostosis decreased from 3.062 and 3.341 to 0.232 and 0.312, respectively. The VNG angle was corrected from 167° and 169° to 180° and 178°, respectively. The correction effect of cerebral deformity and typical maxillofacial deformity was satisfactory. Among the 5 children with sagittal synostosis, 3 cases with correct helmet wearing reported increase of head width, and their narrow biparietal diameter were widened. Besides, their CI recovered to 0.80-0.89, gaining a satisfactory correction result. The other 2 cases had unsatisfactory correction results, and their CI level was below 0.75. The head circumference of one case with multiple craniosynostosis was increased from 400.5 mm to 432.5 mm, and the triangular head gradually returned to normal round appearance. The correction effect was satisfactory. The multiple craniosynostosis children with premature neurodevelopmental delay were reviewed with a normal growth quotient at 6 months post surgery.

Preliminary observation showed that for children with non-syndromic craniosynostosis, early endoscopy-assisted craniectomy and postoperative cranial orthosis therapy can correct their cranial deformities, maxillofacial deformities, and improve the nervous system development to a certain extent.

To describe the clinical outcomes of a cohort of consecutive pediatric moyamoya patients of ischemic type undergoing modified EDAS (encephaloduroarterio-synangiosis).

A retrospective study was conducted on the clinical and radiographic data of 26 patients with moyamoya disease consecutively admitted to Department of Neurosurgery, Children′s Hospital Affiliated to the Capital Institute of Pediatrics in the period from June 2016 to June 2019. The 26 children underwent superficial temporal artery EDAS, superficial temporal artery (STA) EDAS with bilateral frontal encephalogaleoperiosteal synangiosis (EGS), or occipital artery EDAS combined with multiple burr-hole (MBH). During operation, the arachnoid membrane over the M4 segment of MCA was opened under the pathway of arterial band and dural inversion was performed. Neurological function outcomes after the operation were evaluated according to the modified Rankin Scale (mRS).

Among 26 patients with ischemic momyamoya disease, 12 underwent bilateral. A total of 39 surgical procedures were performed and included 37 procedures of superficial temporal artery EDAS, 1 procedure of superficial temporal artery EDAS combined wih bifrontal EGS, and 1 procedure of occipital artery EDAS combined with MBH. One patient developed subcutaneous and intracranial hematomas postoperatively which were resolved by pressure dressing. There was no perioperative death. The follow-up duration of the children was 17.1±1.3 months (3-39 months). Out of 39 procedures, 38 led to the results of TIA (transient ischemic attack)-free or improvement of ischemic stroke without new infarction during 2 months post operation. There was no symptomatic improvement in 1 procedure, and the effectiveness of the operation was 97.4% (38/39). The mRS scores of 26 patients in 3 months after surgery were all scored ≤ 2 points. A total of 29 cases of vascular imaging follow-up examination at 3 months post surgery showed that the branches of the external carotid artery provided blood supply to the brain tissues, consisting of STA (or occipital artery) plus middle meningeal artery (MMA) in 26 cases and merely MMA in 3 cases.

Modified EDAS is a safe and effective procedure for ischemic pediatric moyamoya disease, which could increase blood supply region, enhance the effective rate of cerebral vascular reconstruction and thus improve the neurological functions of the patients.

To explore the clinical characteristics and long-term follow-up results of pituitary gigantism.

We performed a retrospective study on 24 patients with pituitary gigantism who were diagnosed and treated at Chinese Academy of Medical Science and Peking Union Medical College, Peking Union Medical College Hospital from January 1990 to December 2018 and underwent follow-up lasting for at least 1 year. Among them, merely one surgical operation was performed in 9 cases, operation combined with medication in 3, operation combined with radiotherapy in 4, operation combined with drugs and radiotherapy in 7, and merely medication in 1. We analyzed the patient’s basic information, laboratory and imaging data. The patients were divided into the cured group and the non-cured group according to follow-up data, and the differences between the two groups were analyzed.

Of the 24 patients, 20 (83.3%) were males, the median age of onset was 13(P₂₅, P₇₅: 10, 14) years, the median age of diagnosis was 17.0(P₂₅, P₇₅: 14.0, 21.0) years, and the median duration of disease was 4.0 (P₂₅, P₇₅: 2.0, 7.0) years. The first symptom of 19 patients (79.2%) was rapid growth in height. Twenty-four cases were pituitary adenomas, of which 21 (87.5%) were pituitary macroadenomas. The median follow-up time for 24 patients was 3.0 (P₂₅, P₇₅: 2.0, 5.7) years, of which 14 were in the cured group (58.3%) and 10 in the non-cured group (41.7%). Compared with the cured group, the non-cured group had older median age of onset [14 (P₂₅, P₇₅: 13, 15) years vs. 11 (P₂₅, P₇₅: 7, 13) years] old, higher median growth hormone level at diagnosis [58.8 (P₂₅, P₇₅: 20.8, 165.9) μg/L vs. 15.2 (P₂₅, P₇₅): 10.0, 22.5 μg/L], larger maximal diameter of the tumor (3.6 ± 0.8 cm vs. 2.2 ± 1.2 cm), higher proportion of surgical treatment combined with medication and radiotherapy (6/10 vs. 1/14, P=0.009), and the differences were statistically significant (all P<0.05).

Preliminary studies show that pituitary gigantism has the characteristics including male predominance, relatively high incidence of pituitary macroadenomas and high chance of delayed diagnosis. The follow-up data show that the cure rate is low, and it is recommended to pay clinical attention to children and adolescents who grow too fast for the purpose of early diagnosis and treatment.

To investigate the expanded application of Poppen approach in the CNS (central nervous system) tumors.

From January 2004 to June 2018, 311 patients with CNS tumors underwent operation through Poppen approach at Department of Neurosurgery, Nanfang Hospital of Southern Medical University. Their clinical data were retrospectively reviewed. There were 221 cases originating from the pineal region, 23 cases from the thalamus, 31 cases from the midbrain, 7 cases from the cerebellum and 29 cases from the tentorium cerebelli. Postoperative MRI examination was regularly performed to evaluate the extent of tumor resection.

A total of 316 operations, including 3 re-operations due to tumor recurrence and 2 re-operations due to residual tumor, were successfully performed in 311 patients. Postoperative MRI revealed that total resection was achieved in 280 (90.0%) cases, subtotal resection in 10 (3.2%) and partial resection in 21 (6.8%). Among 208 patients suffering from preoperative hydrocephalus, 177 (85.1%) achieved symptomatic improvement after operation. Among 103 patients without preoperative hydrocephalus or with improved hydrocephalus after conservative treatment, 13 (12.6%) suffered from postoperative hydrocephalus. Out of all 311 patients, 3 suffered from postoperative hemiplegia with improved symptoms to different degrees at discharge, and 4 suffered from postoperative coma and included 2 with stable conditions whose families refused therapy and 2 with critical conditions at discharge. There were 5 cases of death due to different causes, including 1 case of acute hydrocephalus who did not undergo timely treatment, 1 case of intracranial infection due to external drainage for hydrocephalus, 1 case of severe cerebral swelling because of damage of the venous system, and 2 cases of multiple organ dysfunction syndrome. According to postoperative pathological examinations, there were 118 cases of germ cell tumor, 72 cases of neuroepithelial tumor, 51 cases of pinealoma, 29 cases of meningioma and 41 cases of other rare types.

The Poppen approach can be extensively applied in the tumors in the areas of thalamus, brain stem tumors and cerebellum in addition to those in the pineal region with favorable outcomes.

To investigate the effect of different treatment schemes on survival of patients with cerebrospinal fluid (CSF) dissemination and leptomeningeal dissemination of gliomas.

A total of 1 036 patients were diagnosed with gliomas and admitted to Department of Radiotherapy, Tianjin Huanhu Hospital from February 2012 to May 2019. Among them, 34 patients were diagnosed as CSF dissemination and/or leptomeningeal dissemination, whose clinical data were retrospectively analyzed in this study. The patients were divided into 3 groups based on the treatment schemes. The palliative treatment group (5 cases) consisted of patients who received only symptomatic and supportive treatment. Fundamental treatment group (15 cases) were patients who underwent radiotherapy, chemotherapy, radiotherapy plus chemotherapy or targeted treatment only. Comprehensive treatment group (14 cases) were patients who underwent simultaneous radiotherapy and chemotherapy (including intrathecal chemotherapy) combined with targeted therapy. We collected the general data of patients, tumor removal degree, pathological type, WHO rating, postoperative radiotherapy and chemotherapy scheme, tumor dissemination time, post-dissemination treatment regimen, post-dissemination survival (PDS), etc. The clinical characteristics of different groups were compared. The survival curve was drawn using the Kaplan-Meier method, and the survival periods of the 3 groups were compared.

Among 3 groups, differences in the patient′s age, gender, WHO rating, pathological type, opening of the ventricle, proximity to the ventricle and pre-treatment KPS (Karnofsky Performance Status)score were not statistically significant (all P>0.05), while the resection degree of previous operation and time of postoperative dissemination were statistically significant (bothP<0.05). The median follow-up time for 34 patients was 19.4 months (2.9-93.2 months). By the last follow-up, there were 11 cases of survival (32.3%) and 23 deaths (67.6%). Among them, all 5 cases(5/5) in the palliative treatment group died, 11 deaths(11/15) were reported in the fundamental treatment group and 7 deaths(7/14) in the comprehensive treatment group. The median PDS of 34 patients was 6.1 months (1.0-20.5 months). The median PDS was 2.1 months (1.0-3.2 months) in palliative treatment group, 5.9 months (2.5-20.5 months) in fundamental treatment group, and 9.3 months (1.0-19.0 months) in comprehensive treatment group. The difference in PDS between 3 groups was statistically significant (χ²= 43.404, P<0.001).

Comprehensive treatment of radiation and chemotherapy combined with targeted therapy can effectively prolong the survival of glioma patients post CSF and leptomeningeal dissemination.

To investigate the effect of siRNA interfering butyrophilin family member BTN3A3 on the apoptosis of glioma cells.

Glioma cell lines (HS683 and U251) and primary glioma cells were cultured and divided into negative control (NC) group (blank cells), Si-1 group and Si-2 group (transfected with plasmids with 1 and 2 sequences, respectively). Western blot was used to analyze the expression levels of BTN3A3 in glioma cell lines and microglia cell line (HMC3). Flow cytometry was used to analyze the changes of cell apoptosis following knockdown of BTN3A3. Glioma tissue obtained during surgical resection was cultured to obtain primary glioma cells. The expression levels of BTN3A3 in the primary cells were examined by Western blot, and changes of cell apoptosis following knockdown of BTN3A3 were detected by flow cytometry.

BTN3A3 was expressed at higher levels in HS683 and U87-MG cell lines than in HMC3 cell line (HS683: 1.12±0.03, U87-MG: 1.08±0.05, HMC3: 0.66±0.02, both P<0.01). The expression levels of BTN3A3 of Si-1 (0.11±0.01) and Si-2 (0.12±0.01) groups in U251 cell line were lower than that of NC group (0.21±0.01) (bothP<0.01). The expression levels of BTN3A3 of Si-1 and Si-2 groups in HS683 cell line were 0.77±0.03 and 0.78±0.04 respectively, which were lower than that of NC group (1.01±0.03) (bothP<0.01). When BTN3A3 was knocked down, the proportions of early apoptotic cells in HS683 cell line (NC: 31.6%, Si-1: 53.7%, Si-2: 63.3%) and late apoptotic cells in U251 cell line (NC: 10.4%, Si-1: 18.9%, Si-2: 26.5%) were increased. BTN3A3 expression level was higher in primary glioma cells (0.75±0.07) than in HMC3 microglia cells (0.55±0.06) (P<0.05). After transfection of siRNA, expression levels in primary glioma cells decreased (Si-1: 0.44±0.01, Si-2: 0.49±0.02, NC: 0.90±0.01, bothP<0.01), whereas the proportion of late apoptotic cells in primary glioma cells was increased (NC: 12.3%, Si-1: 22.6%, Si-2: 18.2%).

Interference of siRNA with butyrophilin family member BTN3A3 promotes cell apoptosis of glioma cell lines and primary glioma cells.

To explore the expression, clinical significance and biological function of HOXB2 in gliomas.

Bioinformatics analysis was employed to retrospectively analyze the transcriptome and information clinical data of 1001 glioma patients in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). Kaplan-Meier (KM) analysis was used to explore the effect of HOXB2 on the survival of patients. Univariate and multivariate Cox regression analysis methods were used to evaluate the effect of HOXB2 on the prognosis of glioma patients. Pearson correlation analysis was used to screen genes related to HOXB2, and gene enrichment analysis was performed on those genes through Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

The expression levels of HOXB2 in gradeⅡ, grade Ⅲ and grade Ⅳ gliomas were significantly different (all P<0.05). Higher tumor grade was associated with higher expression ofHOXB2. The overall survival time of glioma patients in the HOXB2 high expression group was significantly lower than that in the HOXB2 low expression group (P<0.01). CGGA data showed that the expression ofHOXB2 (HR=1.237, 95%CI: 1.094-1.398, P<0.001) and tumor grade(WHO grade Ⅳ) (HR=3.447, 95%CI: 2.456-4.837, P<0.001) were independent prognostic factors. TCGA data showed thatHOXB2 expression (HR=1.580, 95%CI: 1.320-1.892, P<0.001), age (HR=1.037, 95%CI: 1.027-1.048, P<0.001), tumor grade (WHO grade Ⅳ)(HR=2.500, 95%CI: 1.782-3.505, P<0.001) and IDH1 mutation status (HR=0.509, 95%CI: 0.360-0.719, P<0.001) were independent prognostic factors. The results as above suggested that the expression ofHOXB2 was negatively correlated with overall survival in glioma patients. GO and KEGG analysis revealed that the expression of HOXB2 was closely related to extracellular matrix, antigen presentation, inflammation and other pathways. Matrix metalloproteinases (MMPs) showed a significant positive correlation with the expression of HOXB2, suggesting that HOXB2 promoted the invasion of gliomas (all P<0.05).

The expression of HOBX2 is associated with tumor grade which could be used as an independent prognostic indicator in patients with gliomas.