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Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is the active catalytic component of prolyl 4-hydroxylase and plays a crucial role in modulating extracellular matrix hemostasis. P4HA1 has been reported to promote tumor progression by enhancing invasion and angiogenesis. Overexpression of P4HA1 is associated with decreased survival for patients with breast and prostate cancer. However, the prognostic significance of P4HA1 for glioma patients remains undefined.The expression of P4HA1 in 290 gliomas (WHO grade II-IV) and 10 normal brain tissues was examined with TMA-based immunohistochemistry assay. The correlation between P4HA1 expression and clinicopathological parameters as well as the prognosis of glioma patients was investigated.Cytoplasmic expression of P4HA1 is high in 37.93% of all glioma cases, with 44.98% in high-grade gliomas and 19.75% in low-grade gliomas respectively. Increased P4HA1 level was correlated with advanced histological grade (p0.01) and old age (p=0.01). Upregulation of P4HA1, as well as histological grade, was an independent risk factor for unfavorable prognosis. Subgroup analysis demonstrated that high P4HA1 expression was significantly associated with poor prognosis for high-grade gliomas (p0.01) but not for low-grade gliomas.P4HA1 was upregulated in gliomas. High expression of P4HA1 was correlated with the malignancy of gliomas and could serve as a prognostic indicator for patients with high-grade gliomas.

Background: The present study presents 18 cases of Chinese patients harboring a Langerhans cell histiocytosis (LCH) of the skull. Methods: Eighteen consecutive patients were diagnosed as LCH of the skull and confirmed pathologically between March 2002 and February 2014. In the present study, the patients of LCH without skull involvement were excluded. According to disease extent at diagnosis, the 18 LCH patients with skull involvement were divided into three groups: (I) unifocal-monosystem group, including ten cases with solitary skull lesion; (II) multifocal-monosystem group, including two cases with multiple bone lesions and no extra-skeletal involvement; (III) multisystem group, including six cases with LCH lesions involving both skeletal and extra-skeletal system. In unifocal-monosystem group, excision of the skull lesion was performed in eight of ten cases, a low dosage of local radiotherapy and a purposeful observation was accept by the remaining two cases of this group after biopsy respectively. In multifocal-monosystem group, both of the two cases were received chemotherapy. In multi-system group, all the six cases were managed with systemic chemotherapy, after their diagnoses of LCH were confirmed. Results: The mean age at the time of diagnosis was 9.4 years. There was a male predominance in this disease male/female ratio was 3.5:1. In our cases, a skull mass with or without tenderness was the most common chief complaint (13 cases, 72.2%), and frontal bone was the most frequent affected locations of skull (6 cases, 33.3%). In unifocal-monosystem group, nine of ten remained free from LCH, the remain one lesion recurred 22 months after his surgical excision. In multifocal-monosystem group, a complete response (CR) was obtained in one of them, and a stable disease (SD) of multiple osseous lesions was obtained in another one. In the multi-system group, a CR in four cases and a partial response (PR) in one case were obtained, and a progressive disease (PD) was observed in the remaining one. Conclusions: The unifocal-monosystem of LCH of the skull is a clinicopathological entity with a good outcome, and resection, irradiation or purposeful observation are also can be been utilized as the choice of treatment. For the multifocal bone lesions and multisystem lesions of LCH, chemotherapy is an effective treatment as a systemic therapy. There is no enough publication literature to determine guidelines or indications for managing this disease.

Background It is rare for 2 primary tumors to occur simultaneously in a patient. Management of cervical dumbbell schwannomas (CDSs) with concurrent tumors (CTs) requires a specific neurosurgical strategy. The primary objective of this study is to investigate surgical strategies for CDSs with CTs while preserving as much of the mechanically relevant bone structures as possible. Methods Twelve patients with concurrent CTs and CDSs were identified from 3 medical centers. Surgical strategies for CDSs were based on accurate preoperative images and subsequent treatment considerations for CTs. All patients received surgical treatment for CDSs and CTs. Clinical features, surgical considerations for a transforaminal approach (TA), and ultimate outcome were studied retrospectively. Results Gross total resection of CDSs was achieved with endoscopic and microscopic assistance in 9 cases, and subtotal resection was achieved in 3 cases after the head and neck surgeons exposed and removed the extraforaminal anatomy. One patient required an additional hemilaminectomy for the resection of the intraspinal segment. After wound healing, patients were transferred to the appropriate surgical department for surgery on CTs with cervical spine stabilization after a transforaminal approach. Conclusions In most patients, the stability of the cervical spine can be preserved with low invasive microsurgical or endoscopic transforaminal resection. CTs could be surgically treated sequentially after microscopic- and endoscopic-assisted resection of CDSs.

Preoperative prognostic nutritional index (PNI) has been widely demonstrated to predict survival of patients with malignant tumors. Its utility in predicting outcomes in patients with high-grade gliomas (HGG) remains undefined. A retrospective study of 188 HGG patients was conducted. An optimal PNI cut-off value was applied to stratify patients into high PNI (≥52.55, n = 78) and low PNI (

// Qun-Ying Yang 1, * , Cheng-Cheng Guo 1, * , Mei-Ling Deng 2 , Jian Wang 1 , Jing Wang 1 , Fu-hua Lin 1 , Ji Zhang 1 , Xiao-Bing Jiang 1 , Yong-Gao Mou 1 , Zhong-Ping Chen 1 1 State Key Laboratory of Oncology in South China, Department of Neurosurgery/Neuro-Oncology at The Cancer Center of Sun Yat-sen University, Collaborative Innovation Center of Oncology, Guangzhou 510060, China 2 State Key Laboratory of Oncology in South China, Department of Radiotherapy at The Cancer Center of Sun Yat-sen University, Collaborative Innovation Center of Oncology, Guangzhou 510060, China * These authors have contributed equally to this work Correspondence to: Zhong-Ping Chen, email: chenzhp@sysucc.org.cn Keywords: primary intracranial germ cell tumor, clinical diagnosis, diagnostic radiotherapy, diagnostic chemotherapy Received: January 27, 2016 Accepted: June 10, 2016 Published: June 22, 2016 ABSTRACT Background and Objective: Primary intracranial germ cell tumors (GCTs) are a class of heterogeneous tumors. Surgery can quickly relieve tumor compression and provide histological diagnosis. It is very difficult to treat some patients who are unable to be pathologically diagnosed. We aimed to analyze clinically diagnosed GCTs patients. Methods: Patients clinically diagnosed as primary intracranial GCTs were included in this study. Results: From 2002 to 2015, 42 patients clinically diagnosed with primary intracranial GCTs received chemotherapy and/or radiotherapy. Patients were assigned to diagnostic chemotherapy group (25 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 85.8%, 75.0% and 63.6%, respectively. There were no statistically significant difference ( p value = 0.44). Patients were assigned to the group (30 cases) with secretory tumors and the group (12 cases) with non-secretory tumors based on their levels of tumor makers. The 5- year survival rates were 80.7% and 68.6%, respectively. There were no statistically significant difference ( p value = 0.49).The major adverse reactions were grade III - IV bone marrow suppression with an incidence of 35.2% and grade II- III nausea/vomiting with an incidence of 45.8%. Conclusion: Surgical removal of tumor or biopsy is recognized as the most accurate method to determine the pathological property of tumor. But for some patients who can not be pathologically diagnosed, they can receive comprehensive treatments such as chemotherapy combined with radiotherapy, and some of them can still have good responses.

Objectives Malignant gliomas are common primary brain tumors with dismal prognosis. The blood–brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas. Patients and methods Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20 mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3 + 3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded. Results Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322 days (95% CI, 173–471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. Conclusions The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.

To explore the survival of newly diagnosed malignant gliomas patients on combined modality therapy of surgery, radiotherapy and chemotherapy.The data of 122 newly diagnosed malignant glioma patients on combined modality therapy at our center between 2000 and 2010 were retrospectively reviewed and analyzed. The median age was 40 years old (range: 5 - 75) and median Karnofsky performance status score (KPS) 80 (range: 60 - 100). Combined modality therapy consisted of surgery (maximal safety tumor resection), followed by fractionated focal irradiation for a total dose of 54 - 60 Gy and then 4 - 6 cycles of adjuvant chemotherapy including temozolomide or nitrosourea-based regimens or other ones without temozolomide and nitrosourea. The overall and progression-free survivals were analyzed by the Kaplan-Meier method and the influencing factors screened by Cox proportional hazard model.There were grade IV (n = 70) and grade III (n = 52). The median survival periods were 17.0 months for grade IV patients and 36.0 months for grade III ones. The 2, 3, 4 and 5-year survival rates were 32.0% vs 64.8%, 19.6% vs 47.8%, 11.8% vs 32.0% and 5.9% vs 25.4% (P0.01) for grades IV and III patients respectively. The median progression-free survivals were 9.0 vs 12.0 months and 1, 2 and 3-year progression-free survival rates 30.8% vs 50.0%, 12.3% vs 31.4% and 9.2% vs 17.7% (P0.01) respectively. Multivariate analysis revealed that histologic type was an independent prognostic factor.Combined modality therapy of surgery, adjuvant radiotherapy and chemotherapy may improve the survival of patients with malignant gliomas.

Background Brain metastases (BM) from hepatocellular carcinoma (HCC) are extremely rare and are associated with a poor prognosis. The aim of this study was to define clinical outcome and prognostic determinants in patients with BM from HCC. Methods Between January 1994 and December 2009, all patients with HCC and BM treated in Sun Yat-sen University Cancer Center were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors. Results Forty-one patients were diagnosed with BM from HCC, an incidence of 0.47%. The median age at diagnosis of BM was 48.5 years. Thirty-three patients (80.5%) developed extracranial metastases at diagnosis of BM, and 30 patients (73.2%) had hepatitis B. Intracranial hemorrhage occurred in 19 patients (46.3%). BM were treated primarily either with whole brain radiation therapy (WBRT; 5 patients), stereotactic radiosurgery (SRS; 7 patients), or surgical resection (6 patients). The cause of death was systemic disease in 17 patients and neurological disease in 23. Patients in a high RPA (recursive partitioning analysis) class, treated with conservatively and without lung metastases, tended to die from neurological disease. Median survival after the diagnosis of BM was 3 months (95% confidence interval: 2.2-3.8 months). In multivariate analysis, the presence of extracranial metastases, a low RPA class and aggressive treatment, were positively associated with improved survival. Conclusions BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive treatment. The clinical implication of extracranial metastases in HCC patients with BM needs further assessment.

To investigate correlation between the expression of TGF-β1 and the amount of Treg cell in glioma, and evaluate their clinical values in predicting the prognosis of glioma.Double immunohistochemistry staining was used to detect the expression of TGF-β1, CD4 and Foxp3 in 135 specimens of human gliomas (WHO I 18, WHO II 45, WHO III 53, WHO IV 19) and 15 normal brain.OF the 135 specimans of glioma, 58 showed low TGF-β1 expression and 77 (57.03%) showed high TGF-β1 expression while ws not expression in normal brain tissue. Average Treg cell density in glioma was 2. 031/HP, but there was no expression of Treg in normal brain tissue. Expression of TGF-β1 was positively correlated with the mount of Treg in glioma tissues (r = 0.294, P0.01). Compared with the low grade, The levels of TGF-β1 and the amount of Treg cells with significant higher in high-grade glioma, however the mount of Treg had no correlations with Sex, KPS score. The Laplan-Meier analysis showed that there wer significant difference in overall survival (OS) between the TGF-β1 high-expression and low-expression group (P0.001). Cox multivariate analysis showed that TGF-β1 and Treg were not independent prognostic factors (P0.05).Intratumoral of TGF-β1 may relate to the infiltration of Treg cells in glioma tissues. The level of TGF-β1 was obviously increased in high grade. Glioma patients with TGF-β1 or Trg high expression have poorer prognosis, while TGF-β1 and Treg cannot serve as independent prognostic factors of glioma survival time.

The incidence of brain metastasis (BM) from colorectal carcinoma (CRC) is increasing. The objectives of the present study were to explore the clinical characteristics and potential prognostic factors in CRC patients with BM. Between April 1991 and December 2010, all CRC patients treated in the Sun Yat-sen University Cancer Center were retrospectively reviewed and 60 patients were identified to have BM (36 males and 24 females). The association between patients and their tumor characteristics, treatment modality, and survival were statistically analyzed. The median age at diagnosis of BM was 62.5 years. Fifty-three patients (88.3%) developed extracranial metastases at diagnosis of BM. The cause of death was systemic disease in 19 patients and neurological disease in 23 patients. Brain metastases were primarily treated with either whole brain radiation therapy (WBRT; 15 patients), stereotactic radiosurgery (SRS; nine patients), or surgical resection (seven patients). Ten patients received WBRT and SRS, and 19 patients (31.7%) were treated with steroids alone. The median survival after diagnosis of BM was 8 months (95% confidence interval = 4.2–11.8 months). Recursive partitioning analysis (RPA) class, the number of brain lesions, and treatment modality type were significantly associated with survival. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. A low RPA class and a limited number of brain lesions may predict increased survival after therapy for CRC patients with BM.

Background. Radiation-induced temporal lobe necrosis is a rare and serious late complication in irradiated patients with nasopharyngeal carcinoma (NPC). Treatment of radiation-induced temporal lobe necrosis with surgery has been seldom thoroughly investigated. Methods. We retrospectively analyzed the clinical data of 14 patients with radiation-induced temporal lobe necrosis treated with surgical intervention. Results. Radiation-induced temporal lobe necrosis pre- sented as obvious cystic formation or as heterogeneous enhanced nodule on MRI. Among 3 patients with 18 F-fluoro- deoxyglucose ( 18 F-FDG) PET-CT scan, increased uptake of 18 F-FDG was observed in 2 cases. Four patients were anes- thestized nasotracheally and 1 was through tracheostomy dur- ing surgery because of other radiation complications, including trismus and skull base osteoradionecrosis. The temporal approach was applied in all cases, with the removal of bone flap in 11 patients. During follow-up, 1 patient died of exhaustion. Conclusions. Surgery benefits selected patients with NPC with radiation-induced temporal lobe necrosis. The goals of surgery are to relieve the increased intracranial pressure and to establish the accurate diagnosis. V

PURPOSE To explore the feasibility and efficacy of a cell delivery system using amniotic membrane (AM) fixed by a novel biomembrane-fixing device (BMFD) for corneal epithelium reconstruction in rabbits with limbal stem cell deficiency (LSCD). METHODS Sixty female rabbits with LSCD were created and randomly assigned to three groups of 20 each: LSCD rabbits without treatment (the control), LSCD rabbits treated with BMFD-fixed AM (BMFD-AM), and rabbits treated with male human limbal epithelial cells delivered with BMFD-fixed AM (BMFD-AM+cells). They were followed up with slit lamp observation and corneal fluorescein staining for 14 days. Cytokeratin K3 and K4 and mucin 5AC were used to evaluate corneal conjunctivalization. Sry gene detection was used to trace the delivered cells. RESULTS The corneal re-epithelialization time was 5.60 ± 0.46 days in the BMFD-AM+cell group, significantly shorter (P < 0.05) than in the LSCD (12.45 ± 0.65 days) and the BMFD-AM (9.25 ± 0.51 days) groups. Conjunctivalization and neovascularization were observed to be severe in the LSCD group and moderate in the BMFD-AM group. The prevention of conjunctivalization in the BMFD-AM+cell group was evidenced by positive K3/K12 and negative MUC5AC and K4 observed on re-epithelialized corneal epithelium. The histologic sections at different time points and positive Sry gene expression indicated that the delivered cells adhered to the wounded corneal surface and proliferated well. CONCLUSIONS These findings demonstrate that the BMFD with fixed AM served well as a cell delivery system for the ocular surface. The delivered limbal epithelial cells promoted corneal re-epithelialization and prevented corneas from conjunctivalization and neovascularization in rabbits with experimental LSCD.

Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment), the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.

Background Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients. Methods Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed. Results Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients. Conclusions For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients.