Songbai Gui

Assessment of endoscopic treatment for middle cranial fossa arachnoid cysts

BackgroundEndoscopic cystocisternotomy is one of three surgical methods used to treat middle cranial fossa arachnoid cysts. There is debate about which method is the best.ObjectiveThe aim of this study is to evaluate the effectiveness and safety of endoscopic cystocisternotomy for treatment of arachnoid cysts of the middle cranial fossa.MethodsThirty-two patients with arachnoid cysts of the middle cranial fossa who had undergone endoscopic cystocisternal fenestration between 2004 and 2009 were studied retrospectively. Data were obtained on clinical and neuroradiological presentation, indications to treat, surgical technique, complications, and the results of clinical and neuroradiological follow-up.ResultsAmong the 27 patients with symptoms before surgery, 8 had disappearance of symptoms and 17 had improvement of symptoms. The cyst was reduced in size or it completely disappeared in 24 (75%) patients. The incidence rate of complications was 18.8%.ConclusionsEndoscopic cystocisternal fenestration is an effective treatment for symptomatic arachnoid cysts of the middle cranial fossa and should be the initial surgical procedure.

Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

BackgroundDopamine agonists (DAs) are the first-line treatment for prolactinomas, which account for 25–30% of functioning pituitary adenomas, and bromocriptine (BRC) is the only commercially available DAs in China. However, tumors are resistant to therapy in 5–18% of patients.MethodsThe exomes of six responsive prolactinomas and six resistant prolactinomas were analyzed by whole-exome sequencing.ResultsUsing stringent variant calling and filtering parameters, ten somatic variants that were mainly associated with DNA repair or protein metabolic processes were identified. New resistant variants were identified in multiple genes including PRDM2, PRG4, MUC4, DSPP, DPCR1, RP1L1, MX2, POTEF, C1orf170, and KRTAP10-3. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT–qPCR) in 12 prolactinomas and 3 normal pituitary glands. The mRNA levels of PRDM2 were approximately five-fold lower in resistant prolactinomas than in responsive tumors (p < 0.05). PRDM2 protein levels were lower in resistant prolactinomas than in responsive tumors, as determined by Western blotting and immunohistochemical analysis (p < 0.05). Overexpression of PRDM2 upregulated dopamine receptor D2 (D2DR) and inhibited the phosphorylation of ERK1/2 in MMQ cells. PRDM2 showed a synergistic effect with BRC on the inhibition of prolactin (PRL) secretion and MMQ cell viability, and low PRDM2 expression was associated with tumor recurrence.ConclusionsPRDM2 downregulation may play a role in dopamine-agonist resistance and tumor recurrence in prolactinomas.

Expression of estrogen receptor α and growth factors in human prolactinoma and its correlation with clinical features and gender

Background: Many studies demonstrate that growth factors play an important role in the pathogenesis of prolactinoma induced by estrogen. The effects of estrogen are mainly mediated through its nuclear receptor (ERα); however, expression of ERα and growth factors in prolactinoma and healthy pituitary and their relationship remain obscure. Aim: To obtain new insights regarding the expression differences of these factors and their relationship and to investigate the correlation between gender and clinical features in patients with prolactinoma. Subjects and methods: A total of 21 human prolactinomas and 6 healthy human pituitaries were examined for mRNA expression of ERα, basic fibroblast growth factor (bFGF), transforming growth factor α (TGFα), TGFβ1, TGFβ3, and TGFβ receptor type II (TGFβRII) by means of real-time PCR. Patient clinical data was also analyzed. Results: Both PRL level and tumor volume of the male patient group were higher than that of the female patient group. There was a significant correlation between PRL level and tumor volume in the total patient group. Expression of ERα, bFGF, TGFα, and TGFβ3 mRNA levels of the patient group were significantly different from that of the control group. A significant correlation between ERα mRNA levels and PRL levels, tumor volume, TGFβ1 mRNA levels in the total patient group were found. Conclusions: PRL level and tumor volume have a significant difference between genders in prolactinoma patients. ERα and some growth factors may be involved in the tumorigenesis of prolactinoma. ERα could potentially be an effective therapy target for treating prolactinoma.

The role of FSCN1 in migration and invasion of pituitary adenomas.

The prediction of invasion or malignant behavior in PAs remains challenging. FSCN1, an actin-bundling protein, is associated with increased risk of mortality and metastasis in various cancer types. The objective of the study was to evaluate the expression of FSCN1 in 312 PAs cases, and to analyze its association with clinicopathologic features and invasion of PAs, thus serving as a promoter of cancer invasion. In non-function PAs (NFPA), FSCN1 nuclear-positive cases were 53/97 in the invasive group (IPA), and 21/115 in the noninvasive group (nIPA) (ⅹ(2) = 30.65, p = 0.004). FSCN1 cytoplasm-positive cases were 36/97 in IPA, and 8/107 in nIPA (ⅹ(2) = 29.09, p = 0.000). In growth hormone adenomas (GHomas), FSCN1 nuclear-positive were 10/13 in IPA, and 3/37 in nIPA (ⅹ(2) = 23.67, p = 0.000). FSCN1 cytoplasm-positive were 8/13 in IPA, and 2/37 in nIPA (Table 3 ⅹ(2) = 18.94, p = 0.000). Overall, a significant difference was found between FSCN1 expression and tumor size (ⅹ(2) = 46.21, p = 0.000), not age (ⅹ(2) = 2.09, p = 0.148). In the high FSCN1 expression group, 27/137 cases (19.7%) had tumor recurrence, and 10/175 cases (5.7%) in low FSCN1 level (ⅹ(2) = 14.40 p = 0.000). Reduction of FSCN1 suppressed the invasion level of GH3 cells through transwells test. In addition, reduction of FSCN1 can obviously down-regulate the level of Notch1 and DLL3. Our data may help in deciding whether FSCN1 can be a predictor for invasion and recurrence of PAs.

Identification of Differentially Expressed Genes in Pituitary Adenomas by Integrating Analysis of Microarray Data

Pituitary adenomas, monoclonal in origin, are the most common intracranial neoplasms. Altered gene expression as well as somatic mutations is detected frequently in pituitary adenomas. The purpose of this study was to detect differentially expressed genes (DEGs) and biological processes during tumor formation of pituitary adenomas. We performed an integrated analysis of publicly available GEO datasets of pituitary adenomas to identify DEGs between pituitary adenomas and normal control (NC) tissues. Gene function analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) networks analysis was conducted to interpret the biological role of those DEGs. In this study we detected 3994 DEGs (2043 upregulated and 1951 downregulated) in pituitary adenoma through an integrated analysis of 5 different microarray datasets. Gene function analysis revealed that the functions of those DEGs were highly correlated with the development of pituitary adenoma. This integrated analysis of microarray data identified some genes and pathways associated with pituitary adenoma, which may help to understand the pathology underlying pituitary adenoma and contribute to the successful identification of therapeutic targets for pituitary adenoma.

Whole‑exome sequencing identifies variants in invasive pituitary adenomas

Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of tumorigenesis, and most likely contribute to the development of oncocytic change and to the invasive tumor phenotype.

Suppression of MMQ cells by fulvestrant: possible mechanism of action and potential application for bromocriptine-resistant prolactinomas

Bromocriptine is an effective treatment for most prolactinomas. Estrogen receptor (ER) antagonists are an alternative for treating patients with bromocriptine-resistant prolactinomas (BCRP). Previously, we reported that fulvestrant, a selective ER antagonist, significantly inhibited the proliferation of, and prolactin secretion by, MMQ cells, a prolactin-secreting rat pituitary cell line, an exemplary model for prolactinoma. In this study, we used fulvestrant to block ERα expression by MMQ cells and analyzed the expression of β-catenin and Wnt inhibitory factor-1 (WIF1) to investigate the effects of fulvestrant on the Wnt signaling pathway. In addition, we examined the gene expression of ERα, β-catenin and WIF1 in clinical BCRP specimens to explore the correlation between gender and clinical features. There was no significant difference in β-catenin expression between fulvestrant-treated cells and untreated cells, whereas WIF1 expression was higher in the treated cells. In clinical BCRP specimens, ERα expression was higher (especially in male patients), whereas β-catenin expression was similar to normal pituitaries. In addition, WIF1 expression was significantly lower in BCRP specimens than in normal pituitaries. The tumor volume was larger in male patients than in female patients. Prolactin concentration was positively correlated with tumor volume, and a positive linear correlation was observed between ERα expression and tumor volume. In conclusion, the anti-tumor activity of fulvestrant on MMQ cells seems to be associated with ERα and the non-canonical Wnt pathway, and higher ERα levels in male patients with BCRP may contribute to the larger tumor volumes observed. Fulvestrant holds promise as a therapeutic agent for BCRP.

Loss of 15-hydroxyprostaglandin dehydrogenase indicates a tumor suppressor role in pituitary adenomas

15-hydroxyprostaglandin dehydrogenase (15-PGDH) may function as a tumor suppressor that antagonizes the action of the cyclooxygenase-2 (COX-2) oncogene in several types of tumors. However, it is unknown if it has a role in the pituitary. Recently, our group found that 15-PGDH expression was low in prolactin (PRL) secreting adenomas (prolactinomas) and growth hormone (GH) secreting adenomas (GHomas) using fiber-optic BeadArray technology. In this study, we examined the relative expression of 15-PGDH and COX-2 mRNA in clinical specimens and examined the effects of 15-PGDH on GH3 rat pituitary tumor cell proliferation, apoptosis and hormone secretion. 15-PGDH expression was lower and COX-2 expression was higher in prolactinomas and GHomas compared with normal controls. Overexpressed 15-PGDH inhibited tumor cell proliferation and induced apoptosis. It had a significant suppressive effect on mRNA levels and on the secretion of PRL and GH in GH3 cells. The inhibition of cell proliferation was accompanied by the decreased expression of cox-2, matrix metalloproteinase-9 (MMP-9) and B cell leukemia/lymphoma-2 (Bcl-2). These data are suggestive of a previously unrecognized pathway in pituitary tumorigenesis, and this novel observation may shed light on therapeutic strategies for pituitary tumors.

Endoscopic treatment of suprasellar cysts without hydrocephalus.

OBJECTIVE At present, endoscopic treatment is advised as the first procedure in cases of suprasellar arachnoid cysts (SSCs) with hydrocephalus. However, the appropriate therapy for SSCs without hydrocephalus has not been fully determined yet because such cases are very rare and because it is usually difficult to perform the neuroendoscopic procedure in patients without ventriculomegaly given difficulties with ventricular cannulation and the narrow foramen of Monro. The purpose of this study was to find out the value of navigation-guided neuroendoscopic ventriculocystocisternostomy (VCC) for SSCs without lateral ventriculomegaly. METHODS Five consecutive patients with SSC without hydrocephalus were surgically treated using endoscopic fenestration (VCC) guided by navigation between March 2014 and November 2015. The surgical technique, success rate, and patient outcomes were assessed and compared with those from hydrocephalic patients managed in a similar fashion. RESULTS The small ventricles were successfully cannulated using navigational tracking, and the VCC was accomplished in all patients. There were no operative complications related to the endoscopic procedure. In all patients the SSC decreased in size and symptoms improved postoperatively (mean follow-up 10.4 months). CONCLUSIONS Endoscopic VCC can be performed as an effective, safe, and simple treatment option by using intraoperative image-based neuronavigation in SSC patients without hydrocephalus. The image-guided neuroendoscopic procedure improved the accuracy of the endoscopic approach and minimized brain trauma. The absence of hydrocephalus in patients with SSC may not be a contraindication to endoscopic treatment.

Anatomic study of the anterior skull base via an endoscopic transnasal approach.

OBJECTIVES With rapid advances in endoscopic neurosurgery, it has become possible to treat some lesions located in the anterior skull base through a transnasal approach. This anatomic study was undertaken to describe the area of surgical exposure of the anterior skull base afforded by transnasal approaches with an endoscope, as well as to provide references for clinical practice. METHODS Thirty bony skull base specimens (all Chinese) were used, and 10 injected adult cadaver heads (all Chinese) were dissected for a simulated endoscopic transnasal approach to the anterior skull base. The distance between the bilateral optic canals was measured in skull base specimens and the distance between the columella and anterior ethmoid artery or posterior ethmoid artery was measured on both sides in adult cadaver heads. RESULTS The optic canals were 15.13±1.69 mm apart. The distance between the columella and posterior ethmoid artery was 71.01±3.99 mm on the left side and 72.27±3.97 mm on the right side. The distance between the columella and anterior ethmoid artery was 64.811±3.74 mm on the left side and 64.18±3.74 mm on the right side. The endoscopic transnasal approach to the anterior skull base exposed the optic protuberance, sellar floor, crista galli, anterior ethmoid artery, and posterior ethmoid artery. In addition, bilateral olfactory bulbs, olfactory tracts, and optic nerves beneath the dura mater were also revealed. CONCLUSIONS The anatomic data as well as established anatomic landmarks associated with endoscopic surgery would benefit clinical practice.