The clinical significance of inflammatory mediators in predicting obesity and progression-free survival in patients with adult-onset Craniopharyngioma.

BACKGROUND: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. METHODS: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. RESULTS: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. CONCLUSION: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma.

BACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study.

OBJECTIVE: Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. METHODS: We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. RESULTS: Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. CONCLUSIONS: The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.

Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells.

Mechanical interactions between cells and extracellular matrix (ECM) are critical for stem cell fate decision. Synthetic models of ECM, such as hydrogels, can be used to precisely manipulate the mechanical properties of the cell niche and investigate how mechanical signals regulate the cell behavior. However, it has long been a great challenge to tune solely the ECM-mimic hydrogels' mechanical signals since altering the mechanical properties of most materials is usually accompanied by chemical and topological changes. Here, we employ DNA and its enantiomers to prepare a series of hydrogels with univariate stiffness regulation, which enables a precise interpretation of the fate decision of neural progenitor cells (NPCs) in a three-dimensional environment. Using single-cell RNA sequencing techniques, Monocle pseudotime trajectory and CellphoneDB analysis, we demonstrate that the stiffness of the hydrogel alone does not influence the differentiation of NPCs, but the degradation of the hydrogel that enhances cell-cell interactions is possibly the main reason. We also find that ECM remodeling facilitates cells to sense mechanical stimuli.

The effect of endoscopic transsphenoidal somatotroph tumors resection on pituitary hormones: systematic review and meta-analysis.

PURPOSE: Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative effects on pituitary endocrine function, and the pituitary function of somatotroph tumors is a point of particular concern after the operation. This study aimed to conduct a meta-analysis on the effect of endoscopic transsphenoidal somatotroph tumor resection on pituitary function. METHODS: A systematic literature search was conducted for articles that included the evaluation of pituitary target gland before and after endoscopic transsphenoidal pituitary tumor resection and were published between 1992 and 2022 in PubMed, Cochrane, and Ovid MEDLINE. RESULTS: Sixty-eight studies that included biochemical remission rates in 4524 somatotroph tumors were concluded. According to the 2000 consensus, the biochemical remission rate after transsphenoidal endoscopic surgery was 66.4% (95% CI, 0.622-0.703; P = 0.000), the biochemical remission rate was 56.2% according to the 2010 consensus (95% CI, 0.503-0.620; P = 0.041), and with the rate of biochemical remission ranging from 30.0 to 91.7% with investigator's definition. After endoscopic resection, adrenal axis dysfunction was slightly higher than that before surgery, but the difference was not statistically significant. Hypothyroidism was 0.712 times higher risk than that before surgery (OR = 0.712; 95% CI, 0.527-0.961; P = 0.027). Hypogonadism was 0.541 times higher risk than that before surgery (OR = 0.541; 95% CI, 0.393-0.746; P = 0.000). Hyperprolactinemia was 0.131 times higher risk than that before surgery (OR = 0.131; 95% CI, 0.022-0.783; P = 0.026). The incidence of pituitary insufficiency was 1.344 times the risk before surgery after endoscopic resection of somatotroph tumors, but the difference was not statistically significant. CONCLUSIONS: In patients with somatotroph tumors after undergoing endoscopic surgery, the risk of dysfunction and pituitary insufficiency tend to increase, while preoperative thyroid insufficiency, gonadal insufficiency, and hyperprolactinemia will be partially relieved.

The intestinal flora of patients with GHPA affects the growth and the expression of PD-L1 of tumor.

CONTEXT: Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors' growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown. OBJECTIVE AND METHODS: Here we used high-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study of the immune response. RESULT: We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8+ cells. Increased numbers of CD3+CD8+ cells and increased levels of sPD-L1 were detected in peripheral blood. CONCLUSION: These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.

Feasibility of endoscopic endonasal resection of intrinsic third ventricular craniopharyngioma in adults.

Intrinsic third ventricular craniopharyngiomas (IVCs) are usually considered as a contraindication of endoscopic endonasal approach (EEA). The aim of this study is to evaluate the safety and feasibility of EEA for the resection of IVCs based on MRI topographical diagnosis and surgical findings. We reviewed the data of 22 patients who were diagnosed to be IVCs according to five MRI criteria and underwent surgery through EEA. Sixteen IVCs were resected using endoscopic endonasal infrachiasmatic corridor, five IVCs by using endoscopic endonasal suprachiasmatic trans-lamina terminalis corridor, and one IVC by using both the infrachiasmatic and suprachiasmatic corridors. During the operation, all the 22 cases were verified to be IVCs. Gross total resection was achieved in 21 (95.5%) patients. After surgery, visual improvement was observed in 14 (63.6%) patients, no change in 6 (27.3%) patients, and some deterioration in 2 (9.1%) patients. An improvement in intellectual ability was observed in nine (40.9%) patients, no change in twelve (54.5%) patients, and some deterioration in one (4.5%) patient. Fifteen of the 22 patients (68.2%) developed new endocrinological deficit. One postoperative cerebral spinal fluid leakage occurred. EEA can be used as a safe and efficacious approach for the radical resection of IVCs. The combination of the five MRI criteria may serve as an accurate preoperative diagnostic tool to define the topographical relationships between craniopharyngiomas and the third ventricle. The endoscopic transnasal view from below has the advantage of clarifying the relationship between tumors and the third ventricle floor.

Mid-term follow-up surgical results in 284 cases of clival chordomas: the risk factors for outcome and tumor recurrence.

OBJECTIVE: Skull base chordoma (SBC) is rare and one of the most challenging diseases to treat. We aimed to assess the optimal timing of adjuvant radiation therapy (RT) and to evaluate the factors that influence resection and long-term outcomes. METHODS: In total, 284 patients with 382 surgeries were enrolled in this retrospective study. Postsurgically, 64 patients underwent RT before recurrence (pre-recurrence RT), and 47 patients underwent RT after recurrence. During the first attempt to achieve gross-total resection (GTR), when the entire tumor was resected, 268 patients were treated with an endoscopic midline approach, and 16 patients were treated with microscopic lateral approaches. Factors associated with the success of GTR were identified using χ2 and logistic regression analyses. Risk factors associated with chordoma-specific survival (CSS) and progression-free survival (PFS) were evaluated with the Cox proportional hazards model. RESULTS: In total, 74.6% of tumors were marginally resected [GTR (40.1%), near-total resection (34.5%)]. History of surgery, large tumor volumes, and tumor locations in the lower clivus were associated with a lower GTR rate. The mean follow-up period was 43.9 months. At the last follow-up, 181 (63.7%) patients were alive. RT history, histologic subtype (dedifferentiated and sarcomatoid), non-GTR, no postsurgical RT, and the presence of metastasis were associated with poorer CSS. Patients with pre-recurrence RT had the longest PFS and CSS, while patients without postsurgical RT had the worst outcome. CONCLUSION: GTR is the goal of initial surgical treatment. Pre-recurrence RT would improve outcome regardless of GTR.

Development and Application of Three Steps Training Mode for Endoscopic Transnasal Transsphenoidal Approach.

OBJECTIVE: The model of endoscopic transnasal transsphenoidal approach (METTA) were made and the application of the 3-steps training mode in the endoscopic transnasal transsphenoidal approach (ETTA) training was discussed. METHODS: The plastic skull model was used to make a simple METTA model; the multicolor and multi-material 3D printing technology was used to make a METTA simulation model and the perfusion cadaver head specimen was used as the gold standard training model. Then 3 neurosurgeons evaluated the 3 types of models. Level 1 training group only received perfusion cadaveric head specimen training; level 2 training group with 3D printing METTA model plus cadaver head specimen training, and level 3 training group with simple model, 3D printing model and cadaver head specimen training group. The authenticity of the model and the training effect were evaluated according to the operation time and the damage degree to the surrounding structures. RESULTS: The results showed that perfusion cadaveric head specimens scored the highest in each item. The simplified model was superior to the 3D printing METTA in simulating the shape and elasticity of pituitary tumor tissue. The score of surgical skill training was the same as that of 3D printing METTA. In terms of the training effect, the doctors who had received 3 steps training had the highest score, which was better than the other 2 groups. CONCLUSIONS: The application of 3 steps training mode with simple training model, 3D printing model and perfusion cadaver head specimen can improve the effect of ETTA operation training.

Experience of Endoscopic Endonasal Approach for 803 Pituitary Tumors With Cavernous Sinus Invasion.

OBJECTIVE: The aim of this study was to investigate the effectiveness, safety, complications, and prognosis of endoscopic endonasal surgery for pituitary adenomas with cavernous sinus invasion (CSI). METHODS: The clinical data of 803 pituitary adenomas with CSI surgeries performed in our single ward between January 1, 2006 and December 31, 2018 were retrospectively reviewed. The resection degree, bone invasion, endocrine examination, complications, and outcome were retrospectively summarized. RESULTS: Gross total resection was achieved in 394 patients (49.1%) subtotal resection in 171 patients (21.3%) and partial resection in 238 patients (29.6%). Clinically variable analyses showed that there was a significant correlation between CSI and female, older age, operation history, and non-gross total resection (NGTR). Among the pituitary adenomas with CSI, there was a significant correlation between bone invasive and NGTR, Knosp classification, recurrence. K-M curves showed that young age, larger tumors, bilateral invasion, Grade 4 of Knosp classification, NGTR, and bone invasion were associated with pituitary adenomas regrowth. Multivariate analysis revealed that bone invasion, NGTR, and Grade 4 of Knosp classification were independent risk factors for pituitary adenomas regrowth. There was a significant correlation between CSI and female, older age, operation history, and tumor resection degree. CONCLUSIONS: There was a significant correlation between CSI and female, older age, operation history, and tumor resection degree. The patients with CSI and bone invasion were likely to recurrent. Non-gross total resection, bone invasion, and Grade 4 of Knosp classification were independent risk factors for pituitary adenomas regrowth. Endoscopic endonasal surgery is an excellent choice for pituitary adenomas with CSI.

LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis.

BACKGROUND: Dysregulated lncRNA PCAT6 was discovered in many cancers excluding pituitary adenomas (PA). Therefore, we explored the role of PCAT6 in PA in this research. METHODS: Abnormally expressed miRNAs were analyzed by bioinformatics and RT-qPCR. The target and regulator of miR-139-3p were determined by bioinformatics, dual-luciferase reporter assay, or RIP. The correlation among PCAT6, miR-139-3p, and BRD4 was further analyzed. The viability, apoptosis, cell cycle distribution of PA cells, as well as their ability to invade, migrate, and proliferate, were tested after transfection through CCK-8, flow cytometry, transwell, wound healing, and colony formation assays. After construction of transplanted-tumor model in nude mice, cell apoptosis in the tumor was detected by TUNEL. The expressions of PCAT6, BRD4, miR-139-3p, and apoptosis-related factors in PA tissues, cells, or tumor tissues were detected by RT-qPCR, Western blot, or IHC. RESULTS: PCAT6 and BRD4 were high-expressed but miR-139-3p was low-expressed in PA. Both the 3'-untranslated regions of PCAT6 and BRD4 mRNAs were demonstrated to contain a potential binding site for miR-139-3p. PCAT6 was positively correlated to BRD4, and miR-139-3p was negatively correlated to PCAT6 and BRD4. MiR-139-3p mimic, shPCAT6 and siBRD4 inhibited the viability, migration, invasion, and proliferation of PA cells while inducing apoptosis. MiR-139-3p mimic and shPCAT6 inhibited the cell cycle progression of PA cells, decreased the weight and volume of the xenotransplanted tumor, and reduced the levels of Bcl-2 and BRD4 while enhancing the levels of Bax, miR-139-3p, and Cleaved caspase-3. MiR-139-3p inhibitor caused the opposite effect of miR-139-3p mimic and further reversed the effect of shPCAT6 on on PA cells. CONCLUSION: PCAT6 regulated the progression of PA via modulating the miR-139-3p/BRD4 axis, which might provide a novel biomarker for the prevention, diagnosis, and treatment of PA.

Up-regulation of the expressions of MiR-149-5p and MiR-99a-3p in exosome inhibits the progress of pituitary adenomas.

This study explored the function of microRNAs (miRNAs) in invasive pituitary adenomas (IPA), and developed a microRNA-exosome strategy for the disease treatment. Differentially expressed miRNAs and tumor-associated markers in IPA, non-invasive pituitary adenoma (NIPA), and rat pituitary adenoma cells were identified by bioinformatics analysis and qRT-PCR. Then, the cells were treated by miR-149-5p and miR-99a-3p mimics or inhibitors, or incubated with modified exosome with overexpressed or silenced miRNAs. The cell behaviors were analyzed by molecular experiments. Xenograft assays were constructed by injection of pituitary adenoma cells and exosome into NU/NU nude mice. Tumor size, weight, and expressions of markers related to miRNAs and angiogenesis were determined. Target genes for miR-99a-3p and miR-149 were predicted and verified by bioinformatics analysis and molecular experiments. Twenty differentially expressed miRNAs were identified, among which miR-99a-3p and miR-149 were inhibited in both pituitary adenoma cells and tissues significantly. Expressions of E-cadherin and p53 were down-regulated, while those of MMP-2, MMP-9, N-cadherin, Vimentin, and VEGF were up-regulated in pituitary adenoma cells and tissues, especially in IPA. Further experiments revealed that overexpressed miR-149 and miR-99a-3p inhibited the growth and metastasis of pituitary adenoma cells and tube formation of endothelial cells. MiR-149 and miR-99a-3p overexpressed by exosome showed similar suppressive effects on cell viability, metastasis, tube formation ability, in vivo tumor growth, and expressions of angiogenesis-related markers. Further analysis showed that NOVA1, DTL, and RAB27B were targeted by miR-99a-3p. This study found that overexpressed miR-149-5p and miR-99a-3p induced by exosome could suppress the progression of IPA. 1. MiR-149-5p and miR-99a-3p affect the expression of EMT- and ECM-related markers and tumor-related genes in rat pituitary adenoma cells treated with exosomes. 2. Exosome inhibited the tumor growth. 3. Overexpressed miR-149-5p and miR-99a-3p induced by exosome.

Suprasellar arachnoid cysts: systematic analysis of 247 cases with long-term follow-up.

At present, limited data exists to discuss the characteristics of suprasellar arachnoid cysts (SACs). The aim of this study is to elucidate the relationship between characteristics of cysts and outcomes, quantitatively analyze improvement in hydrocephalus, and evaluate the risk factors for the prognosis of SACs treated by endoscope. From June 2002 to 2017 December, 247 cases of SACs treated by endoscope in Beijing Tiantan Hospital were included in this study. The severity of hydrocephalus was evaluated by Evans' index (EI). The results showed that the slit-valve and the transparent/thin membrane were noted in 86.2% and 76.5% of overall patients, respectively, and the distribution differences among age-groups were statistically significant (p < 0.01). After a mean follow-up duration of 73.1 months, 18 patients underwent a reoperation. Ventriculocystostomy (VC) (hazard ratio (HR), 3.37; 95% confidence interval (CI), 1.2-9.47; p = 0.024) and history of treatment (HR, 3.98; 95% CI, 1.31-12.31; p = 0.015) were adverse factors for reoperation rate. MRI at 1-year follow-up revealed mean decreases of 78.4% and 9.13% in cyst size and EI. No paraventricular edema was an adverse factor associated with the improvement in hydrocephalus (HR, 11.22; 95% CI, 5.43-23.18; p < 0.01). These results indicated that ventriculocystocisternostomy (VCC) and no history of treatment is favorable factors for prognosis of SACs treated by endoscope. If feasible, VCC is the optimal choice for SACs. Slit-valve phenomenon and transparent/thin membrane are correlated with age but did not influence the outcomes of endoscopic fenestration. The mechanism for the expansion of cysts may be different between child and adult patients. Paraventricular edema is a favorable factor for the improvement in hydrocephalus after endoscopic surgery.

Suprasellar arachnoid cysts in adults: clinical presentations, radiological features, and treatment outcomes.

A tendency for suprasellar arachnoid cysts (SACs) to occur in young children is known. Data of adult SACs were rare in previous reports. The aim of this study is to discuss their clinical presentations, radiological features, and treatment outcomes based on 23 adult patients who underwent endoscopic fenestration in our hospital between January 2003 and December 2018. Preoperative cyst volume ranged from 12.3 to 72.5 cm3 (mean 39.8 ± 19.8). Endocrine disorders occurred in 7 (30.4%) patients. Hydrocephalus was observed in 20 patients. In the patients with hydrocephalus, the mean preoperative Evans' index (EI) (%) and frontooccipital horn ratio (FOHR) (%) were 44.8 (ranged 32.2-63.4) and 49.6 (ranged 36.7-59.8), respectively. A bivariate correlation showed significant positive association between preoperative cyst volume and preoperative EI or FOHR (Pearson correlation, r = 0.607, p = 0.005; r = 0.583, p = 0.007). The slit-valve phenomenon was observed in 13 (56.5%) patients. Pale/tenacious cyst walls were observed in 12 (52.2%) patients. Postoperatively, all patients achieved the improvement in clinical symptoms and a decrease in cyst size. The mean decreases in cyst volume, EI, and FOHR were 64.7%, 7.89%, and 5.8%, respectively. A bivariate correlation indicated the irrelevance between the postoperative cyst volume and postoperative EI or FOHR (Pearson correlation: r = 0.37, p = 0.11; r = 0.43, p = 0.054). These results reveal that there are a few differences in several aspects between adult patients and child patients. The severity of hydrocephalus is correlated with cyst size in adult patients. Additionally, the excellent outcomes in adult SACs can be obtained by endoscopic fenestration.

Research advances on the immune research and prospect of immunotherapy in pituitary adenomas.

BACKGROUND: Pituitary adenomas are one type of intracranial tumor, which can be divided into microadenoma (≤ 1 cm), macroadenoma (> 1 cm), and giant adenoma (≥ 4 cm) according to their diametral sizes. They are benign, typically slow-progressing, whereas the biological behavior of some of them is invasive, which presents a major clinical challenge. Treatment of some pituitary adenomas is still difficult due to drug resistance or multiple relapses, usually after surgery, medication, and radiation. At present, no clear prediction and treatment biomarkers have been found in pituitary adenomas and some of them do not cause clinical symptoms, so patients are often found to be ill through physical examination, and some are even found through autopsy. With the development of research on pituitary adenomas, the immune response has become a hot spot and may serve as a novel disease marker and therapeutic target. The distribution and function of immune cells and their secreted molecules in pituitary adenomas are extremely complex. Researchers found that infiltration of immune cells may have a positive effect on the treatment and prognosis of pituitary adenomas. In this review, we summarized the advance of tumor immunity in pituitary adenomas, revealing the immunity molecules as potential biomarkers as well as therapeutic agents for pituitary adenomas. CONCLUSION: The immune studies related to pituitary adenomas may help us find relevant immune markers. At the same time, the exploration of immunotherapy also provides new options for the treatment of pituitary adenomas.

A good choice for the patients with prior failed ventriculoperitoneal shunt treatment of suprasellar arachnoid cysts: endoscopic fenestration.

To investigate the effectiveness of endoscopic fenestration in the patients with prior failed ventriculoperitoneal (VP) shunt treatment of suprasellar arachnoid cysts (SACs). Between 2012 and 2018, four pediatric patients of SACs with previous failed VP shunt treatment were surgically treated using endoscopic ventriculocystocisternostomy (VCC) in our hospital. The clinical symptoms, imaging data, and surgical outcomes were collected and analyzed retrospectively. A literature review is provided with regard to the reasons of shunt failure and surgical outcome of further endoscopic fenestration in the previously reported patients of SACs with prior failed VP shunt. For the 4 cases, the initial clinical symptoms relieved or even disappeared after shunt placement, but, respectively, recurred 2, 6, 11, and 6 months later. MR scans were conducted when the clinical symptoms reappeared and showed a cyst had greatly enlarged after shunt placement. Furthermore, VP shunt-related slit ventricle was also demonstrated in 3 cases. Clinical improvement and cysts shrinkage occurred in all 4 patients after VCC. Slit ventricle and hydrocephalus were also resolved. Three patients had their shunt apparatus removed after VCC, and another patient's guardian refused to remove the shunt apparatus. Subdural hematoma occurred in one case after shunt apparatus removal. Four patients have been stable during follow-up period (mean follow-up 26.5 months). All the three patients whose VP shunt were removed were shunt independence. There were 24 patients who underwent endoscopic fenestration as an alternative to the failed VP shunt treatment in the published reports. Added our 4 patients to the published group, the effective rate of endoscopic fenestration for SACs following previous failed VP shunt treatment was approximately 93% (26/28). Of the 24 patients, the shunt apparatuses were in situ or reimplantation in 9 patients due to shunt dependence. The correction to recognize the SAC is the first condition to select the optimal management philosophy. The analysis of the series suggests endoscopic operation is still an effective and safe option in the SAC patients with previous failed VP shunt, and the shunt apparatus can be removed for some patients. The short interval time between shunt operation and endoscopic fenestration is conductive to return patients to the shunt-free state.

SNF5 as a prognostic factor in skull base chordoma.

The current study aimed to characterize SNF5 expression and investigate the relationship between SNF5 and clinicopathological features in skull base chordoma. 48 patients diagnosed with skull base chordoma were enrolled in this study. Tissue microarray and immunohistochemistry were performed to evaluate the expression of SNF5 in skull base chordoma. Kaplan-Meier survival analysis was used to assess survival. Multivariable Cox regression analysis was used to identify risk factors affecting patient survival. The H-scores for cytoplasmic SNF5 ranged from 124.47 to 254.52. Low expression of SNF5 was correlated with shorter overall survival (OS) (p = 0.021). Patients with age > 55 years old had shorter progression free survival (PFS) and OS times than patients whose age ≤ 55 years old (p = 0.005 and 0.003, respectively). The gross total resection group showed longer PFS than the non-gross total resection group (p = 0.024). Females showed shorter PFS times than males (p = 0.033). Multivariable Cox regression analysis showed that age, extent of resection and sex were independent prognostic factors for PFS (p = 0.010, 0.013 and 0.042, respectively). Age was an independent prognostic factor for OS (p = 0.010). Our study indicate that low expression of SNF5 is associated with poor prognosis in skull base chordoma.

Application of endoscopic third ventriculostomy for treating hydrocephalus-correlated Chiari type I malformation in a single Chinese neurosurgery centre.

The correlation between hydrocephalus and Chiari type I malformation (CIM) has been debated since Chiari's first descriptions of CIM but some studies have shown that CIM and hydrocephalus (HCP) could cause symptoms/disease of each other or vice versa. Recent research has found that treatment focused on hydrocephalus with ventricle enlargement also provides alleviation of CIM and even of syringomyelia. However, the lack of consensus among previous studies left unanswered the question of how endoscopic third ventriculostomy (ETV) addresses CIM and why it fails. Ten symptomatic hydrocephalic patients associated with CIM underwent ETV from October 2002 to May 2012. The clinical features and neuroimaging of all patients were reviewed. Statistical analysis was applied to evaluate the changes in the tonsillar ectopia and the ventricle dilation after operation. The mean follow-up period of this series was 92 months (range 24-163 months). Eight patients (80%) remained shunt free or experienced symptom relief following ETV. The remaining two patients were identified as failures due to the deterioration of symptoms or subsequent hindbrain decompression. Endoscopic third ventriculostomy provides an effective treatment for hydrocephalus associated with CIM, which can relieve HCP and improve the symptoms of CIM in most patients. The clinical outcomes are related to the major cause of the tonsillar herniation.

Global expression profile of tumor stem-like cells isolated from MMQ rat prolactinoma cell.

BACKGROUND: Cancer stem cells (CSCs), which have been isolated from various malignancies, were closely correlated with the occurrence, progression, metastasis and recurrence of the malignant cancer. Little is known about the tumor stem-like cells (TSLCs) isolated from benign tumors. Here we want to explore the global expression profile of RNA of tumor stem-like cells isolated from MMQ rat prolactinoma cells. METHODS: In this study, total RNA was extracted from MMQ cells and MMQ tumor stem-like cells. RNA expression profiles were determined by Agilent Rat 8 × 60 K Microarray. Then we used the qRT-PCR to test the result of Microarray, and found VEGFA had a distinct pattern of expression in MMQ tumor stem-like cells. Then WB and ELISA were used to confirm the VEGFA protein level of tumor sphere cultured from both MMQ cell and human prolactinoma cell. Finally, CCK-8 was used to evaluate the reaction of MMQ tumor stem-like cells to small interfering RNAs intervention and bevacizumab treatment. RESULT: The results of Microarray showed that 566 known RNA were over-expressed and 532 known RNA were low-expressed in the MMQ tumor stem-like cells. These genes were mainly involved in 15 different signaling pathways. In pathway in cancer and cell cycle, Bcl2, VEGFA, PTEN, Jun, Fos, APC2 were up-regulated and Ccna2, Cdc25a, Mcm3, Mcm6, Ccnb2, Mcm5, Cdk1, Gadd45a, Myc were down-regulated in the MMQ tumor stem-like cells. The expression of VEGFA were high in tumor spheres cultured from both MMQ cell and human prolactinomas. Down-regulation of VEGFA by small interfering RNAs partially decreased cell viability of MMQ tumor stem-like cells in vitro. Bevacizumab partially suppressed the proliferation of MMQ tumor stem-like cells. CONCLUSIONS: Our findings characterize the pattern of RNA expression of tumor stem-like cells isolated from MMQ cells. VEGFA may act as a potential therapeutic target for tumor stem-like cells of prolactinomas.