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Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the activation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting apoptosis, suppressing proliferation and angiogenesis of tumors. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future.

The current studies associated with tumor biology continue to describe a high correlation between tryptophan (Trp) metabolism and tumor progression. These findings reflect the complex underlying mechanism of tumor development and highlight the need to explore additional drug targets for carcinoma-associated diseases. In our study, we reported that elevated Trp metabolism was observed in highly malignant glioma tumor tissues from patients. The elevated Trp metabolism in glioma cells were induced by the overexpression of Trp 2,3-dioxygenase 2 (TDO2), which further contributed to the production of the metabolite kynurenine (Kyn). Subsequently, the Kyn derived from Trp metabolism was able to mediate the activation of the aryl hydrocarbon receptor (AhR) and downstream PI3K/AKT signals, resulting in the strengthening of tumor stemness and growth. Meanwhile, the activation of the AhR could promote the process of epithelial-mesenchymal transition in gliomas through a TGF-β-dependent mechanism, leading to enhanced tumor invasion in vitro and in vivo. Inhibition of the AhR using StemRegenin 1 was demonstrated to suppress glioma growth and improve the outcome of traditional chemotherapy in subcutaneous tumor-bearing mice, representing a promising therapeutic target for clinical glioma treatment.

Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.

Microvascular decompression (MVD) is the first choice of surgery for hemifacial spasm (HFS). MVD surgery for vertebral artery (VA)-associated HFS is more difficult than for non-VA-associated HFS. There is controversy about the cure rate and complication of MVD for HFS in previous studies. We searched PubMed, Web of Science, and Embase for relevant publications. Based on the search results, we compared the outcomes of MVD for VA-associated HFS and non-VA-associated HFS. At the same time, we analyzed spasm-free rates and the complications and assessed the relationship between VA-associated HFS and gender, left side, and age. For analysis, six studies that included 2952 patients in the VA-associated group and 604 in the non-VA-associated group were selected. The effective rate of MVD was not significantly different between both groups (OR = 1.16, 95% CI 0.81-1.67, P = 0.42). Compared to non-VA-associated group, the transient complications (OR = 0.64, 95% CI 0.46-0.89, P = 0.008) and permanent complications (OR = 0.28, 95% CI 0.15-0.54, P = 0.0001) occurred more frequently in VA-associated group. The rate of hearing loss was significantly higher in VA-associated HFS than non-VA-associated HFS (OR = 0.35, 95% CI 0.19-0.64, P = 0.0007); the facial paralysis after operation was not significantly different between both groups (OR = 1.25, 95% CI 0.91-1.72, P = 0.17). There were older patients (WMD = 3.67, 95% CI 3.29-4.05, P 0.00001) and more left-sided HFS (OR = 0.23, 95% CI 0.19 - 0.29, P 0.0002) in the VA-associated HFS group than non-VA-associated HFS group, while the non-VA-associated HFS group was female-dominated (OR = 1.58, 95% CI 1.32 - 1.89, P 0.00001). Both groups achieved good results in MVD cure rates. In VA-associated HFS, the complication rate of decompression and the rate of hearing loss after operation were higher than in non-VA-associated HFS, but the facial paralysis after operation was similar in both groups, and most complications were transient and disappeared during follow-up. VA-associated HFS is more prevalent in older adults, less prevalent in women, and more predominantly left-sided. More clinical studies are needed to better compare the efficacy and complication of MVD between both groups.

Purpose We aimed to describe and emphasize the qualitative and etiological diagnosis of Cushing disease combined with empty sella. Methods We reported a 54 y/o female patient who was diagnosed as Cushing syndrome and was qualitatively diagnosed as Cushing disease through endocrine function test. However, the first enhanced MRI examination only found the empty sella. The consistent results of all endocrine function tests led us to conduct the second enhanced MRI of pituitary microadenomas and finally found pituitary nodules on the background of empty sella after careful analysis of imaging films. Finally, the patient accepted surgical treatment and was followed up well. Conclusion The empty sella is not necessarily all hypopituitarism, and it may be hyperpituitarism or both in some cases. Standardized endocrine function tests and advanced imaging technology can play decisive roles for qualitative and etiological diagnosis.

Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan–Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 μM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 μM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Pigmented tumors are rare neoplasm of central nervous system. Melanocytic tumor, including primary and metastatic lesions, is the most common type. Owing to the rarity, the differential diagnosis of pigmented tumors and clinical management of melanocytic tumor remain challenge. Therefore, focusing on melanocytic tumors, the clinical, radiological, histopathological features and treatment outcomes were presented and analyzed in this study. We identified 22 melanocytic tumors, 2 melanotic medulloblastomas, 2 melanotic ependymomas and 1 melanotic schwannoma. Compared with metastatic melanocytic tumors (MMTs), primary melanocytic tumors (PMTs) were characterized by younger age (36.11 ± 17.96 vs. 51.69 ± 12.58 years, p = 0.0262), lower possibility to be multiple lesions (11.1%vs. 61.5%, p = 0.0306), higher proportion of hypointensity on T2-weighted images (66.7% vs. 15.4%, p = 0.0260) and higher frequency in black appearance (77.8% vs. 23.1%, p = 0.0247). During the follow-up, 4 PMTs and 11 MMTs (71.4%) experienced tumor progression. PMTs had better prognosis than MMTs that progression-free survival (PFS) rate of PMT was 50.0% but decreased to 23.1% for MMTs at 12 months (p = 0.0123). Cox proportional hazards regression revealed that multiplicity of tumor was an independent predictor for PFS. None of patient with multiple tumors was in PFS after 12 months’ follow-up whereas PFS rate was 40.5% for single tumor (p = 0.0002). In conclusion, radiological appearances, especially hypointensity on T2-weighted images, might be an indication for PMT. MMTs are more likely to be multiple intraparenchymal masses in elder patients located in supratentorial region. Current treatments included operation, radiotherapy and chemotherapy are not competent to control tumor progression and other therapeutic modalities are urgently needed.

Glioma initiating cells (GICs), also known as glioma stem cells, display the capacity to recapitulate the functional diversity within the tumor. Despite the great progress achieved over the last decades, defining the key molecular regulators of GICs has represented a major obstacle in this field. In our study, data from The Cancer Genome Atlas database illustrated a relationship between C-X-C motif chemokine receptor 4 (CXCR4) expression and the survival of glioma patients. Mechanistically, we further indicated that CXCR4 mediated the upregulation of Kruppel like factor 5 (KLF5), a zinc-finger-containing transcription factor, to facilitate the proliferation of GICs. What's more, CXCR4 also enhanced the chemoresistance through KLF5/Bcl2-like 12 (BCl2L12) in glioma. The elevated expression of KLF5 and BCL2L12 induced by CXCR4 was dependent on phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (AKT) signaling. Importantly, combined application of temozolomide and a CXCR4 inhibitor efficiently reversed CXCR4 mediated drugs resistance and improved anticancer effects in vivo. Collectively, our findings confirmed that CXCR4 promoted GICs proliferation via the KLF5/BCL2L12 dependent pathway, which may enrich the understanding of GICs and help drive the design of efficacious therapeutic strategies.

Background Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years. Methods Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients’ quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated. Results Thirty-six patients with a mean follow-up period of 61.6 months (range 13–123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4–96 months) and 38 months (range 4–125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470–0.756) and 0.939 (95% CI 0.772–0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154–0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118–0.956) result in significantly longer PFS in patients with SFT/HPC. Conclusions Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.

Non-functional pituitary adenomas (NFPAs) are one of the most prevalent pituitary adenoma subtypes. The lack of reliable screening approach for NFPAs for the insidious clinical course usually leads to delays in medical therapy and consequently worse prognosis. Hence, we employed a sequence cohort (patient: control, 6:2) and a validation cohort (patient: control, 22:8) to develop a serum exosomal miRNA profile-based method for NFPA screening and prognosis prediction. We found that a total of 1,395 kinds of human miRNA were detected. Compared with healthy donors, 18 up-regulated and 36 down-regulated miRNAs showed significant expression alterations in NFPA patients. Target genes of differentially expressed miRNAs are mainly enriched in axonogenesis and cancer-associated terms. After validation, hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p were promising biomarkers for NFPA, in which miR-486-5p was the most competent one. After a median of 33 months of prospective follow-up, exosomal hsa-miR-486-5p also was an efficient predictive biomarker for progression or relapse of NFPAs. By protein-protein interaction network construction of hsa-miR-486-5p targeted genes, the core modules revealed a high possibility that exosomal hsa-miR-486-5p regulated tumor progression by epigenetic regulation of MAPK signaling pathways. In conclusion, exosomal hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p are candidate biomarkers for diagnosis and screening of NFPAs. More importantly, prospective follow-up reveals that hsa-miR-486-5p can be regarded as a significant predictor for prognosis of NFPAs.

Although well-documented from pathological aspect, the clinical features and outcomes of acromegaly with mammosomatotroph (MSA) and mixed somatotroph-lactotroph adenoma (MSLA) are seldom reported. Thus, in this study, we analyzed and reported the clinical data about MSAs and MSLAs. We retrospectively reviewed medical records of patients with acromegaly in our institution during 2008–2017. Growth hormone (GH)-secreting adenomas were categorized into pure somatotroph adenoma (PSA), MSA and MSLA based on inclusion and exclusion criteria. Clinical information and treatment outcomes during follow-up were analyzed by univariate and multivariate methods. Among 94 patients within this cohort, PSAs, MSAs, and MSLAs accounted for 53, 28 and 13 cases, respectively. MSAs often had smaller size, lower frequency of cavernous sinus invasion and higher gross total resection (GTR) rate. MSLAs were characterized by bigger tumor size, higher frequency of preoperative hyperprolactinemia, and lower GTR rate. Thus, MSLAs had worse long-term biological remission rate than MSAs and PSAs (15.4% vs. 50.0% and 26.4%, p = 0.0371). Gender (male, OR = 0.784, p = 0.011) and tumor volume (OR = 0.784, p = 0.020) were independent predictors for long-term biological remission in binary logistic regression. Subgroup analyses indicated that postoperative nadir GH level (GH-7, HR = 1.242, p = 0.001) was the only risk factor for tumor recurrence for patients with GTR. Our results provide valuable insights into clinicopathological features of acromegaly. MSAs were relatively smaller lesions with better prognosis. MSLAs were more aggressive with massive size, invasiveness and preoperative hyperprolactinemia. Tumor size and GH-7 were significantly associated with biological remission and tumor relapse after GTR, respectively.

High-grade meningiomas in ventricles are rare, where most published series only include a few patients. A retrospective analysis was performed on the clinical features, radiological findings, and treatment outcomes of 26 patients with high-grade meningiomas in lateral ventricles who were surgically treated in our hospital between July 2008 and July 2016. A female predilection (female/male = 1.4:1) was observed with a mean age of 42.4 years. Headache and/or vomiting (65.3%) were the most common initial symptom, and with symptom duration time ranging between 7 days and 5 years (mean 8.5 months). The lateral ventricle trigone area was the most common site (80.7%). Twenty-two patients (84.6%) obtained gross total resection. The 2007 WHO classification was used to classify 22 (84.6%) meningiomas as grade II and the remaining four tumors were graded III. These tumors accounted for a recurrence rate of 38.5% (10 of 26 patients) and a mortality rate of 11.5% (3 deaths) during the follow-up periods. The recurrence rate after the gross total resection was 27.3% (6 of 22 patients). Radiotherapy was administered as an adjuvant treatment in 12 patients (46.2%) after surgery. There were 4 recurrences out of the 12 patients who received radiotherapy and 6 of the 14 patients relapsed without radiotherapy (p = 0.58). The subtotal resection was considered a risk factor for recurrence. The postoperative radiotherapy seemed to have little significance for the high-grade meningiomas in the lateral ventricles. Long-term follow-up is required, regardless of the resection grade, and reoperation is feasible for patients with recurrence.

Although pituitary adenomas (PAs) are regarded as benign neoplasm, efficient postoperative management of PAs, especially invasive PAs, is still a major challenge for neurosurgeons. Thus, in order to verify the effect of postoperative surveillance alone for invasive PAs and identify helpful predictive factors of relapse after initial surgery, a series of 107 cases of surgically gross-totally resected invasive PAs were retrospectively investigated. With regarded to pituitary function, the preoperative incidence of hypothyroidism was higher than that of hypoadrenocorticism and hypogonadism (66.4% vs. 31.8% and 29.9%; p 0.001). Tumors extended into sphenoid sinus or cavernous sinus may be less likely to develop hypoadrenocorticism or hypogonadism. Postoperative relapse was found in 35 cases (32.7%) during a median follow-up of 27 months. The overall relapse rates were 12.3, 28.9 and 38.4% at 1, 3 and 5 years, respectively. Tumor size was the exclusive independent risk factor for relapse. Higher relapse rates presented in large invasive PAs (more than 3.45 cm) were 24.5, 48.9 and 59.2% at 1, 3 and 5 years, respectively. In conclusion, preoperative larger tumors shared significantly higher risk of relapse after initial surgical total resection. Due to the relatively high relapse rate, close surveillance should be executed in strict rotation in postoperative management of gross-totally resected invasive PAs. Moreover, special attention should be payed to tumors with diameter of more than 3.45 cm for more than half of them relapsed in 5 years.

Peizhi Zhou,1,* Yue Cao,2,* Xiaoxiao Liu,3 Ting Yu,3 Qian Xu,3 Chao You,1 Xiang Gao,1,3 Yuquan Wei2 1Department of Neurosurgery, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pathology, Clinical Medicine College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China *These authors contributed equally tothis work Background: Gene therapy has recently shown considerable clinical benefit in cancer therapy during the past few years, and the application of this choice in cancer treatments is increasing continually. Gli1 is an ideal candidate target for cancer gene therapy and is important for tumorigenesis. Methods: In this study, we developed a novel gene delivery system with a self-assembly method by using a 1,2-dioleoyl-3-trimethylammonium-propane and methoxy poly (ethylene glycol)-poly(lactide) copolymer (DMP), with zeta potential of 32.7 mV and measuring 35.6 nm. The effect of this delivery system was tested in vitro and in vivo.Results: DMP showed good performance in delivering siRNA to glioma cells in vitro with high transfection performance (98%). Moreover, DMP–Gli1si shows a satisfactory anti-glioma effect via induction of cell apoptosis and cell growth inhibition in vitro. Furthermore, for subcutaneous tumor-bearing mice, treatment with the DMP–Gli1si complex significantly inhibited tumor growth by inhibiting Gli1 protein expression, promoting apoptosis, and reducing proliferation. Conclusion: The complex of Gli1 siRNA and DMP may potentially play an important role as a new drug in the clinical treatment of gliomas. Keywords: glioma, gene therapy, Gli1, MPEG-PLA, DOTAP

Giant prolactinomas represent a rare entity of pituitary tumors so that the management of these patients is still a prevalent challenge at present. Paying special attention to the treatment strategy and outcomes, we presented a large series of 42 cases looking forward to share our understanding and experience in management of these patients. Male patients accounted for 71.4% of this series and were relatively younger (35.70±2.42 vs. 52.00±3.55 years, p=0.0011) and harbored bigger tumors (14.57 vs. 7.74 cm3, p=0.0179) compared to females. Almost all of these tumors showed suprasellar extension (97.6%) and cavernous sinus invasion (92.9%). Dopamine agonist represented an efficient method to control PRL concentrations (98.8%) and reduce tumor burdens (81.2 %). PRL normalization was detected in 13 out of the 27 patients initially treated with bromocriptine (BRC) whereas none of the 14 patients with first-line operation gained a normalization of PRL concentration after surgery. Although there was no reliable predictor of tumor response, First PRL reduction was a predictive criterion for the nadir PRL level during the long-time period of follow-up for first-line bromocriptine treatment. In conclusion, patients with giant prolactinomas did not gain more benefits from initial surgery. Dopamine agonist (BRC) should be first-line treatment for giant prolactinomas whereas operation merely served as a remedy for acute compression symptoms and dopamine agonist resistance. Consecutive monitoring of serum PRL levels in the early stage of initial BRC treatment is useful for evaluation of therapeutic effect and further therapeutic decision.

Objective Atypical pituitary adenomas were relatively more malignant lesions defined by WHO criteria. However, not all of them show clinically aggressive behavior. Thus, the current WHO criteria of atypical adenoma didn’t seem to be enough to distinguish clinically aggressive adenoma. Therefore, we would like to identify other clinical factors in a cohort of atypical pituitary adenomas to a better identification of clinical aggressiveness. Patients and Methods In order to verify predictors of clinically aggressive phenotype among atypical pituitary adenomas, we retrospectively analyzed the clinical characteristics and therapeutic outcomes of consecutive 49 cases. Results Totally, 26 cases were identified as clinically aggressive pituitary adenoma. Clinically aggressive lesions were more likely to be functional (46.2% vs. 17.4%, p = .0388) and be detected in males (65.4% vs. 21.7%, p = .0037). Clinically aggressive adenomas also had higher Ki-67 index [5.0 (5.3)% vs. 4.1 (1.3)%, p = .0011] and presented bigger tumor size [11.83 (11.95) cm3 vs. 5.39 (6.08) cm3, p = .0174]. In multivariate analysis, gender (p = .017), functional status (p = .009) and Ki-67 index (p = .024) were independent predictors of clinical aggressiveness. Further analysis revealed that Ki-67 index of more than 4.45% was associated with worse progression-free survival. Conclusions Gender, functional status, tumor size and Ki-67 index ≥ 4.45% were associated with clinical aggressiveness. A clinicopathological classification of pituitary adenomas may be useful to determine who should be under closer radiological follow-up or followed multimodal treatment strategy.

Tumor-associated fibroblasts are the most abundant population in tumor stroma and impact on tumor initiation and progression. However, the biological function of tumor-associated fibroblasts in pituitary adenomas has not been fully elucidated to date. So, this study aims to clarify the function and significance of primary cultured pituitary adenoma-derived tumor-associated fibroblasts on rat pituitary adenoma cells. We identified primary cultured tumor-associated fibroblasts and normal fibroblasts based on the expression of α-smooth muscle actin as well as morphology. Furthermore, we investigated cell biological influences on rat pituitary adenoma cells through indirectly co-culturing tumor-associated fibroblasts with GH3 cells and subcutaneous xenograft model. All sorts of fibroblasts showed positive staining for α-smooth muscle actin. But α-smooth muscle actin and vascular endothelial growth factor highly expressed in invasive pituitary adenoma-derived tumor-associated fibroblasts compared to non-invasive pituitary adenoma-derived tumor-associated fibroblasts and normal fibroblasts. Besides, invasive pituitary adenoma-derived tumor-associated fibroblasts promoted the proliferation of GH3 cells in vitro as well as tumor growth in vivo. Finally, vascular endothelial growth factor was highly expressed in tumor specimens co-injected with invasive pituitary adenoma-derived tumor-associated fibroblasts. Our results suggested that invasive pituitary adenoma-derived tumor-associated fibroblasts displayed apparent growth promotion effects on rat pituitary cells both in vitro and in vivo accompanied by over-expression of vascular endothelial growth factor in invasive pituitary adenoma-derived tumor-associated fibroblasts and tumor specimens.

Pediatric germ cell tumors (GCTs) involving the basal ganglia and thalamus are relatively rare neoplasms which have not been extensively described. We here summarize the clinical and radiological features of a series of such tumors and discuss optimal treatment strategies based upon our experience. A total of 15 pediatric patients with basal ganglionic and thalamic GCTs were treated between 2011 and 2016 at West China Hospital. Epidemiological characteristics, clinical features, imaging findings, and treatment strategies were reviewed retrospectively. GCTs constituted 28% (15/53) of pediatric basal ganglionic and thalamic tumors in our institution between 2011 and 2016. There were 12 males and 3 females with mean age of 11.7 ± 2.8 years (range, 7–16 years). The most common initial manifestation was hemiparesis (n = 13, 86.7%), followed by headache (n = 5, 33.3%), vomiting (n = 3, 20.0%), cognitive disturbance (n = 2, 13.3%), and seizure (n = 1, 6.7%). No tumors were incidentally detected. The mean duration of the symptoms before diagnosis was 4.4 ± 3.9 months (range from 9 days to 13 months). The maximum diameters of the lesions ranged from 3.2 to 6.5 cm (mean 4.7 ± 1.1 cm). Cysts were seen in tumors in MRIs in 11 patients (73%), intratumoral hemorrhages in 3 (20%), calcification in 2 (13%), and there was obstructive hydrocephalus in 1 (7%). Of note, hemiatrophy was observed in 9 cases (60.0%). The mean follow-up for the 15 patients was 28 months (range, 9–54 months), and no patients were lost. During the follow-up period, all patients (9 cases) with germinomas responded well to radiotherapy, and no recurrence was observed. Among 4 patients with mixed nongerminomatous germ cell tumor, 2 suffered tumor recurrence after treatment. Neurological deficits improved or remained unchanged in 12 patients but 3 developed new dysfunction including significant cognitive disturbance and hemiparesis. Pediatric GCTs in the basal ganglia and thalamus are not as rare as previously considered. Tumor markers should be tested routinely for tumors in these sites in young patients. Optimal treatment strategy based on accurate diagnosis and comprehensive clinical assessment should be recommended.

Background Spontaneous spinal epidural hematoma (SSEH) is a rare neurosurgical emergency. It presents as acute spinal cord compression and usually requires surgical decompression. The patients who will benefit most from decompression surgery are unknown, and the factors associated with prognosis remain controversial. The purpose of our study was to identify the clinical features, treatments, and main factors related to the prognosis of SSEH. Methods We reviewed the records of 24 patients treated for SSEH from September 2010 to January 2016 at West China Hospital. Clinical features, radiologic images, treatment methods, and clinical outcomes were reviewed retrospectively. To ascertain which factors were related to outcomes, statistical analysis was performed. Results Among 24 patients, 19 presented with severe initial neurologic deficits (American Spinal Injury Association grade A–C) underwent decompressive surgery, and the remaining patients (initial American Spinal Injury Association grade D or E) received conservative treatment. Among the 19 patients in the operation group, seven (36.8%) had good outcomes, whereas 12 (63.2%) had poor outcomes. All patients in the conservative group had good outcomes. Conclusions SSEH is a rare but serious illness. It is more likely that SSEH arises from a ruptured internal vertebral venous plexus. The initial neurologic status is the determining factor influencing the treatment method and clinical outcome. The number of involved segments cannot be used to decide the treatment method or predict prognosis. Patients with shorter operative intervals appear to have better neurologic recovery.

Metastatic colorectal cancer is a stumbling block in colorectal cancer management due to limited treatment approaches and unfavorable prognosis. Angiogenesis is essential in tumor development and metastasis. Vascular endothelial growth factor receptor (VEGFR) targeted anti-angiogenesis drugs have gain inspiring achievements in cancer treatment. Apatinib is a novel small molecular VEGFR-2 tyrosine kinase targeted drug with poor water-solubility, showing anti-tumor ability in some solid tumors. In this study, PEG modified liposomal Apatinib (Apatinib-Lipo/PEG) was synthesized and applied for colorectal cancer treatment. Results showed that Apatinib-Lipo/PEG could attenuate proliferation and induce apoptosis of CT26 cells. Moreover, Apatinib-Lipo/PEG significantly reduced tumor growth in colorectal peritoneal model as well as subcutaneous model without obvious toxicity. The anti-tumor mechanisms included inhibiting tumor proliferation, promoting tumor apoptosis and suppressing tumor angiogenesis. Thereafter, the application of Apatinib-Lipo/PEG would be very promising in colorectal cancer treatment.

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (

Primary pilocytic astrocytoma (PA) of the spine is extremely rare and most published case series only include only a few patients. We attempted to explore the clinical features, radiological findings, and treatment outcomes of patients with spinal PA. Sixteen spinal PA patients who were surgically treated in our hospital between April 2008 and June 2018 were included in this retrospective study. An integrative analysis was performed regarding spinal PA patients by extracting from published studies on PubMed. The 16 patients with spinal PA included eight male and eight female patients with a mean age of 29.1 years. Ten cases (62.5%) had masses located in the cervical segments, five (31.3%) had masses in the thoracic segments, and one (6.2%) had masses in the sacral canal. All the patients were treated surgically with 13 gross total resections (GTRs, 81.3%) and three subtotal resections (STRs). The mean follow-up period was 40.4 months. These tumors accounted for a recurrence rate of 37.5% (6 of 16 patients) and no death during the follow-up periods. The influencing factors of recurrence were mainly STR, gene mutation (NF-1 and H2-K27M), and the number of segments involved. The mean recurrence-free survival duration was 19 months. The imaging features of spinal PA are heterogeneous, and the definitive diagnosis requires pathological support. GTR is the standard therapy for spinal PAs, although patients with GTR are still likely to relapse. The regular spinal magnetic resonance imaging follow-ups are required regardless of the resection status. Reoperation is feasible for patients with recurrence.

Intrasellar meningiomas are rare tumors that have the ability to mimic non-functioning pituitary adenomas. The majority of meningiomas are slow-growing and benign, therefore an intrasellar meningioma with malignant histological features is extremely rare. The present study describes the case of a malignant diaphragm meningioma that was controlled through combined chemotherapy, following subtotal surgical resection. The patient's symptoms ceased and no tumor recurrence was detected at the 3-year follow-up. Hormone levels were also observed as normal. Further investigation of similar cases may aid in achieving an accurate pre-operative diagnosis. This would prove particularly beneficial in regards to intrasellar meningiomas due to their specific location and surgical treatment. The present study analyzes the requirement of chemotherapy for the treatment of these unique tumors.

Objective Acromegalic patients with macro- or giant adenomas often had poor prognosis after surgery. Somatostatin analogues (SSAs) show high effectiveness in both tumor shrinkage and serum GH reduction. But the role of SSAs in pre-surgical treatment and the management among macro- and giant adenomas remains controversial. Patients and Methods A total of 100 acromegalic patients with macro- or giant adenomas that underwent surgery in our institution between January 2010 and December 2016 were enrolled in the current retrospective study. The relationships between several potential parameters and surgical outcomes were further analyzed. Results The overall long-term remission rate was 45% accompanied by gross total resection (GTR) rate of 44%. GTR (adjusted OR = 16.346; p = .001) and nadir GH level on OGTT 7 days after surgery (GH-7, adjusted OR = 0.660, p = .039) showed predictive significance for remission after surgery. Tumor size and invasiveness as well as cavernous sinus invasion were risk factors for residual tumor. For invasive macro- or giant adenomas, 6 of 15 patients achieved long-term remission with SSA pre-treatment whereas none of the 18 patients without any preoperative treatment was endocrine controlled. Conclusions Acromegalic patients did not gain more benefits from SSAs pretreatment. But, pre-treatment with SSA could be recommended to patients with invasive macro- or giant adenomas for significant improvement in long-term remission. GTR and GH-7 could be significant predictors in postoperative management of macro- or giant adenomas.

Objective Central neurocytoma (CN) is a rare central nervous system tumor the optimal management strategy of which remains controversial because of their rarity. Detailed information on CN is necessary to establish optimal management strategies. The purpose of this study was to show the clinical features, treatments, and long-term clinical outcomes of CN. Methods A total of 63 patients with CN were surgically treated between 1995 and 2016 at West China Hospital. All pathologically proven CN cases were identified. Epidemiologic characteristics, clinical features, imaging features, functional outcomes, overall survival, and progression-free survival according to multimodal treatments were reviewed retrospectively. Results There were 29 males and 34 females, with a median age of 29 years (range, 15–58 years). Thirty-four patients underwent gross total resection (GTR) and 29 patients underwent subtotal resection (STR). The surgical approaches to CNs in this study included a transcortical approach (39 cases) and an interhemispheric transcallosal approach (24 cases). There were no differences in functional outcomes or initial extent of resection according to the surgical approach used. The extent of resection was GTR in 34 patients (54.0%), and STR in 29 patients (46.0%). At the median follow-up of 74 months (range, 6–205 months), the actuarial 5-year and 10-year overall survival were 93.3% and 85.4%. At the last follow-up, 8 patients had experienced tumor progression. The 5-year and 10-year progression-free rate was 73.4% and 57.5%. The initial extent of resection and multimodal treatment was not related to overall survival; however, the actuarial local control rate differed significantly according to the initial extent of resection and multimodal treatment. Conclusions CN is a rare type of World Health Organization grade II primary brain tumor with a tendency to recur. Complete resection of CNs with maximal safety remains the primary treatment to minimize local progression. Adjuvant radiotherapy should be considered in patients receiving incomplete resection. The long-term clinical outcomes of CN after multimodal treatment seem to be satisfactory.

The purpose of this paper is to study invasiveness, tumor features and clinical symptoms of pediatric pituitary adenoma, and to discuss some inconclusive results in prior studies. We retrospectively reviewed 34 cases of children (

Intraventricular meningiomas are rather rare and only represent a small proportion of all intracranial meningiomas. Data are still limited toward this peculiar entity and surgical resection remains challenging for neurosurgeons. The purpose of present study is to demonstrate clinical features, surgical treatment, and potential risk factors determined long-term prognosis of intraventricular meningiomas. A total of 89 surgically treated and histopathologically confirmed intraventricular meningiomas were identified in our institution from 2008 to 2018. Clinical features, neuroimaging findings, surgical records, and prognosis data were extracted and reviewed retrospectively. Group comparison and recurrence-free survival analysis were performed. Female predominance was well established with a sex radio of 2.1:1. Raised intracranial pressure and decline of visual acuity were 2 chief symptoms that patients generally complained of. Preoperative magnetic resonance imaging (MRI) scans were performed in all patients and there was a trend toward lateral ventricular meningiomas were larger in size than others (P = .07). Superior parietal lobule and temporal approach were widely adopted and lateral/4th ventricular meningiomas were more easily to acquire total tumor resection as compared with 3rd ventricular meningiomas (P = .03). After an average follow-up of 57.3 months, 6 patients experienced recurrence of disease in our series. Individuals with subtotal resection (P

Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. Methods: We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. Results: We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. Conclusions: ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change.