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Brain and Spinal Cord Tumours

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Childhood Brain Tumours
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Klinger PH, Andrade AF, Delsin LE, et al.
Inhibition of SHH pathway mechanisms by arsenic trioxide in pediatric medulloblastomas: a comprehensive literature review.
Genet Mol Res. 2017; 16(1) [PubMed] Related Publications
Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment. Several new drugs aimed at SHH modulation are currently under development. This review focuses on the role of arsenic trioxide, a drug well established in clinical practice and probably an under-explored agent in medulloblastoma management, in the SHH pathway.

Liu Z, Wang J, Li Y, et al.
MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase.
Tumour Biol. 2017; 39(2):1010428317691429 [PubMed] Related Publications
Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.

Sato R, Nakano T, Hosonaga M, et al.
RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.
Biomed Res Int. 2017; 2017:8032910 [PubMed] Free Access to Full Article Related Publications
Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

Glebauskiene B, Liutkeviciene R, Vilkeviciute A, et al.
Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development?
Dis Markers. 2017; 2017:5839528 [PubMed] Free Access to Full Article Related Publications
Purpose. To determine if the MMP-9 genotype has an influence on development of pituitary adenoma (PA). Methodology. The study enrolled n = 86 patients with PA and n = 526 healthy controls (reference group). The genotyping of MMP-9 was carried out using the real-time polymerase chain reaction method. Results. Our data demonstrated that the MMP-9 (-1562) C/C genotype was more frequent in PA group than in healthy controls (81.4% versus 64.6%, p = 0.002); C/C genotype was more frequently present in PA females compared to healthy control females, 81.5% versus 64.6%, p = 0.018, as well. MMP-9 (-1562) C/C genotype was frequently observed for all subgroups: noninvasive and invasive, nonrecurrence, and inactive PA compared to healthy controls: 81.8% versus 64.6%, p = 0.021; 81.0% versus 64.6%, p = 0.041; 81.8% versus 64.6%, p = 0.005; 100.0% versus 64.6%, p < 0.001, respectively. MMP-9 (-1562) C/C genotype was more frequent in inactive PA compared to active PA: 100.0% versus 71.4%; p < 0.001. Conclusion. MMP-9 (-1562) C/C genotype plays a role in nonrecurrence, inactive, and invasive as well as in nonivasive PA development.

Long H, Liang C, Zhang X, et al.
Prediction and Analysis of Key Genes in Glioblastoma Based on Bioinformatics.
Biomed Res Int. 2017; 2017:7653101 [PubMed] Free Access to Full Article Related Publications
Understanding the mechanisms of glioblastoma at the molecular and structural level is not only interesting for basic science but also valuable for biotechnological application, such as the clinical treatment. In the present study, bioinformatics analysis was performed to reveal and identify the key genes of glioblastoma multiforme (GBM). The results obtained in the present study signified the importance of some genes, such as COL3A1, FN1, and MMP9, for glioblastoma. Based on the selected genes, a prediction model was built, which achieved 94.4% prediction accuracy. These findings might provide more insights into the genetic basis of glioblastoma.

Volkov AA, Filis AK, Vrionis FD
Surgical Treatment for Leptomeningeal Disease.
Cancer Control. 2017; 24(1):47-53 [PubMed] Related Publications
BACKGROUND: Advancements in cancer treatment have led to more cases of leptomeningeal disease, which requires a multimodal approach.
METHODS: Treatment modalities are reviewed from a neurosurgical standpoint, focusing on intrathecal chemotherapy and shunting devices. Potential complications and how to avoid them are discussed.
RESULTS: The Ommaya reservoir and the chemoport are used for administering intrathecal chemotherapy. Use of ventriculo-lumbar perfusion can efficiently deliver chemotherapeutic agents and improve intracerebral pressure. Shunting systems, in conjunction with all of their variations, address the challenge of hydrocephalus in leptomeningeal carcinomatosis. Misplaced catheters, malfunction of the system, and shunt-related infections are known complications of treatment.
CONCLUSIONS: From an oncological perspective, the surgical treatment for leptomeningeal disease is limited; however, neurosurgery can be used to aid in the administration of chemotherapy and address the issue of hydrocephalus. Minimizing surgical complications is important in this sensitive patient population.

Sahebjam S, Forsyth PA, Smalley KS, Tran ND
Experimental Treatments for Leptomeningeal Metastases From Solid Malignancies.
Cancer Control. 2017; 24(1):42-46 [PubMed] Related Publications
BACKGROUND: Leptomeningeal metastasis is a consequence of advanced solid malignancies and has limited treatment options. It is possible that it is becoming more common as the leptomeninges act as a sanctuary site for recurrence from systemic cancer.
METHODS: Potential targeted and immunotherapy agents for the most common types of solid-tumor leptomeningeal metastasis are reviewed, as are their dosing/delivery strategies and novel, immunological approaches.
RESULTS: Historically, patients with leptomeningeal metastasis have been excluded from clinical trials, and data on the management of leptomeningeal metastasis come from single case reports and retrospective analyses.
CONCLUSION: For the first time ever, published reports suggest the tide may be turning in this challenging disease.

Rigakos G, Liakou CI, Felipe N, et al.
Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis.
Cancer Control. 2017; 24(1):9-21 [PubMed] Related Publications
BACKGROUND: Neoplastic meningitis is a complication of solid and hematological malignancies. It consists of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid.
METHODS: A literature review was conducted to summarize the clinical presentation, differential diagnosis, laboratory values, and imaging findings of neoplastic meningitis.
RESULTS: Neoplastic meningitis is an event in the course of cancer with a variable clinical presentation and a wide differential diagnosis. In general, characteristic findings on gadolinium-enhanced magnetic resonance imaging and the presence of malignant cells in the cerebrospinal fluid remain the cornerstones of diagnosis. However, both modalities do not always confirm the diagnosis of neoplastic meningitis despite a typical clinical picture.
CONCLUSIONS: Clinicians treating patients with cancer should be aware of the possibility of neoplastic meningitis, especially when multilevel neurological symptoms are present. Neoplastic meningitis can be an elusive diagnosis, so clinician awareness is important so that this malignant manifestation is recognized in a timely manner.

Gutiérrez-Rodríguez A, Hansberg-Pastor V, Camacho-Arroyo I
Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells.
Biomed Res Int. 2017; 2017:1295087 [PubMed] Free Access to Full Article Related Publications
Progesterone-induced blocking factor (PIBF) is a progesterone (P4) regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM) from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM) blocked this effect. PIBF (100 ng/mL) increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12-48 h) and U251 (24 and 48 h) cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

Yao PS, Lin ZY, Zheng SF, et al.
Coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms: A case report and literature review.
Medicine (Baltimore). 2017; 96(5):e6012 [PubMed] Free Access to Full Article Related Publications
RATIONALE: There were a few case reports concerning epidermoid tumor coexisted with multiple cerebral aneurysms. Here, we present one case of coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms and performed a literature review.
PATIENT CONCERNS: A 42 years old male patient was admitted to our institution with complaints of headache and dizziness.
INTERVENTIONS: The radiological examinations showed a hypointense lesion in the right parasellar and petrous apex region and an ipsilateral saccular aneurysm originated from the M2-M3 junction of the right middle cerebral artery (MCA) and a saccular aneurysm of the clinoid segment of right internal carotid artery (ICA).
INTERVENTIONS: The patients underwent a right frontotemporal approach for removal of the epidermoid tumor and clipping of the MCA aneurysm in one stage. The aneurysm located at the clinoid segment of ICA was invisible and untreated during operation.
OUTCOMES: No postoperative complications were found in the patient. The patient's follow up after 5 years of surgical treatment was uneventful, and the untreated aneurysm remains stable.
LESSONS: The coexistence of intracranial epidermoid tumor and cerebral aneurysm is a rare event. The secondly inflammation in cerebral arterial wall may be responsible for the aneurysm formation. Surgical treatment of the intracranial epidermoid tumor and cerebral aneurysm repair may be an optimal scheme in one stage.

Sun Z, Cao Y, Zhai LZ
Java brucea and Chinese herbal medicine for the treatment of cholesterol granuloma in the suprasellar and sellar regions: A case report and literature review.
Medicine (Baltimore). 2017; 96(5):e5930 [PubMed] Free Access to Full Article Related Publications
RATIONALE: A cholesterol granuloma (CG) is usually found in the middle ear, papilla, orbits, petrous apex, and choroid plexus, but is highly uncommon in the skull. In spite of benign clinicopathological lesions, bone erosion can be seen occasionally in the patient with CG. The optimal treatment strategy is radical surgery, but complete excision is usually impossible due to anatomical restrictions and a risk of injury to the key structures located nearby. Here, we report a patient with CGs in the suprasellar and sellar regions who was successfully treated with Java brucea and Chinese herbal medicine.
PATIENT CONCERNS: A 31-year-old man presenting with progressive decreased vision in both eyes was analyzed.
DIAGNOSES: A skull magnetic resonance imaging (MRI) scan showed a low-density tumor in the uprasellar and sellar regions and histopathological examination revealed a CG.
INTERVENTIONS: The patient was referred the surgery and radiotherapy. In the meantime, brucea soft capsules and herbal medicine combined were administered to him.
OUTCOMES: The related clinical symptoms and signs resolved significantly after several months, as his therapy progressed. The patient showed no sign of recurrence during the treatment period. Furthermore, he was still alive and disease-free at 37 months of follow-up visit.
LESSONS: Overall, brucea soft capsules and a Chinese herbal formula treatment combined could be beneficial in improving the patient's quality of life with CG in the skull.

Omodaka S, Ogawa Y, Sato K, et al.
Preoperative embolization and immediate removal of a giant pituitary adenoma: a case report.
BMC Res Notes. 2017; 10(1):63 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Giant pituitary adenomas, with maximum diameter of at least 40 mm, continue to involve high surgical risks despite recent advances in microsurgical and/or endoscopic surgery. We treated a case of giant pituitary adenoma with preoperative endovascular embolization in an attempt to reduce blood loss.
CASE PRESENTATION: A 48-year-old Japanese Woman presented with severe right visual disturbance. Magnetic resonance imaging revealed a giant pituitary adenoma with maximum diameter of 82 mm. Angiography revealed significant tumor stain, with blood supply mainly from the branches of the right meningohypophyseal trunk. These feeding arteries were endovascularly embolized with n-butyl cyanoacrylate. Subsequently, the tumor was safely removed by transsphenoidal surgery in two stages. The patient showed significant improvement of visual disturbance postoperatively, and was discharged without other neurological deficit. The surgical policy was explained preoperatively to the patients and written informed consents were obtained.
CONCLUSIONS: Preoperative embolization of a giant pituitary adenoma is a useful procedure that can potentially decrease the morbidity and mortality of this devastating tumor.

Tang K, Kong X, Mao G, et al.
Primary cerebral malignant melanoma: A case report with literature review.
Medicine (Baltimore). 2017; 96(4):e5805 [PubMed] Free Access to Full Article Related Publications
Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs.We report an uncommon case of primary cerebral malignant melanoma-a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions.We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers' reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary.After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy.It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors.

Kong X, Li D, Kong Y, Zhong D
Malignant adenohypophysis spindle cell oncocytoma with repeating recurrences and a high Ki-67 index.
Medicine (Baltimore). 2017; 96(4):e5657 [PubMed] Free Access to Full Article Related Publications
Adenohypophysis spindle cell oncocytoma (ASCO) is a rare tumor recently reported by Roncaroli et al in 2002. This tumor is considered a grade I tumor by the World Health Organization.We report a rare case of malignant ASCO with repeating recurrences and a high Ki-67 index-a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological tests.We represent a 30-year-old man who had suffered from headaches, diplopia, and impaired visual field and acuity. His magnetic resonance imaging revealed an abnormal sellar mass and was originally misdiagnosed as a pituitary macroadenoma. We present detailed analysis of the patient's disease course and review relevant literature.When surgically treated, the specimen revealed a typical histopathology pattern of ASCO. The tumor recurred for several times and the patient underwent 3 surgeries and 1 γ-knife treatment, which was accompanied by a continuously increasing Ki-67 index.This is the first reported case of malignant ASCO (WHO III-IV grade). Despite its rarity, ASCO should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas.

Jin H, Guo ZN, Luo Y, et al.
Intracranial dermoid cyst rupture-related brain ischemia: Case report and hemodynamic study.
Medicine (Baltimore). 2017; 96(4):e5631 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Spontaneous rupture of intracranial dermoid cyst is a rare but serious clinical event that can result in cerebral ischemia. Cerebral vasospasm and vasculitis are considered as potential mechanisms of dermoid cyst rupture-related cerebral ischemia. However, the hemodynamic mechanisms between cerebral ischemia and dermoid cyst rupture are not well known.
PATIENT CONCERNS: A 55-year-old, right-handed man was admitted to our hospital with sudden receptive aphasia and right-sided hypoalgesia. Brain magnetic resonance imaging (MRI) revealed a ruptured dermoid cyst and watershed infarcts in the left hemisphere. Then brain magnetic resonance angiography disclosed mild stenosis in the left middle cerebral artery (MCA), and further high-resolution MRI demonstrated it was caused by an unstable atherosclerosis plaque. Transcranial Doppler of the patient showed a decreasing tendency of peak systolic velocity (PSV) of the left MCA at different time points after the stroke (from 290cm/s at day 6 to 120cm/s at day 30), indicating a transient vasospasm. However, the time course of dynamic cerebral autoregulation (dCA) seemed different from the PSV. The patient's dCA reached its lowest point at day 8 and was restored at day 10. The time course of dCA indicated a "called procedure" of a cerebrovascular regulating function to deal with the stimulation in subarachnoid space.
DIAGNOSES: A dermoid cyst rupture-related cerebral infarction was diagnosed in this patient.
INTERVENTIONS: Aspirin (100 mg/d) and atorvastatin (20 mg/d) were given to the patient. A neurosurgical operation was strongly recommended to minimize the risk of further injury of the ruptured dermoid cyst; however, the patient refused the recommended treatment.
OUTCOMES: The neurological deficit of the patient was significantly improved on 30 days follow-up.
LESSONS: We found that the spread of cyst contents through the subarachnoid and/or ventricular system can induce a vasospasm. Then, dCA was "called" to deal with the stimulation in the subarachnoid space. Compromised dCA seems to be one of the compensatory of cerebral vasospasm after a dermoid cyst rupture.

Yu YL, Yang YJ, Lin C, et al.
Analysis of volumetric response of pituitary adenomas receiving adjuvant CyberKnife stereotactic radiosurgery with the application of an exponential fitting model.
Medicine (Baltimore). 2017; 96(4):e4662 [PubMed] Free Access to Full Article Related Publications
Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome.A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model.The overall tumor control rate was 94.1% in the 36-month (range 18-87 months) follow-up period (mean volume change of -43.3%). Volume regression (mean decrease of -50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of -3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9).Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value according to relative distribution. An exponential decay model can be used to calculate the time course of tumors that are ultimately controlled.

Lee JK, Rho YJ, Jeong DM, et al.
Diagnostic Clue of Meningeal Melanocytoma: Case Report and Review of Literature.
Yonsei Med J. 2017; 58(2):467-470 [PubMed] Free Access to Full Article Related Publications
In this report, the patient was pre-diagnosed as meningioma before surgery, which turned out to be meningeal melanocytoma. Hence, we will discuss the interpretation of imaging and neurological statuses that may help avoid this problem. A 45-year-old man had increasing pain around the neck 14 months prior to admission. His cervical spine MR imaging revealed a space-occupying, contrast-enhancing mass within the dura at the level of C1. The neurologic examination revealed that the patient had left-sided lower extremity weakness of 4+, decreased sensation on the right side, and hyperreflexia in both legs. Department of Neuroradiology interpreted CT and MR imaging as meningiom. The patient underwent decompression and removal of the mass. We confirmed diagnosis as meningeal melanocytoma through pathologic findings. Afterwards, we reviewed the patient's imaging work-up, which showed typical findings of meningeal melanocytoma. However, it was mistaken as meningioma, since the disease is rare.

Duan K, Asa SL, Winer D, et al.
Xanthomatous Hypophysitis Is Associated with Ruptured Rathke's Cleft Cyst.
Endocr Pathol. 2017; 28(1):83-90 [PubMed] Related Publications
Xanthomatous hypophysitis is a rare inflammatory disease of the pituitary gland that can mimic a neoplastic lesion clinically and radiologically. Its pathogenesis remains largely unknown, although recent evidence suggests that pituitary inflammation may occur as a secondary reaction to mucous content released from a ruptured cyst. In a series of 1221 pituitary specimens, we identified seven cases of xanthomatous hypophysitis. Six patients had complete radiological and biochemical workup preoperatively: a cystic-appearing pituitary mass was identified in all six patients (100%) with a mean size of 2.0 cm (range 1.4-2.5 cm) on imaging, and pituitary endocrine dysfunction was noted in five patients (83.3%). In all cases, the pituitary mass was resected through an endoscopic transsphenoidal approach. Pathological examination revealed the presence of foamy macrophages admixed with variable amounts of giant cells and chronic inflammatory cells, confirming the diagnosis of xanthomatous hypophysitis. Additionally, all cases presented with concurrent findings of ruptured Rathke's cleft cyst, with the exception of one patient who had previous surgery for a Rathke's cleft cyst, followed by recurrence and diagnosis of xanthomatous hypophysitis. While accurate distinction of hypophysitis from a pituitary neoplasm can be problematic in the preoperative setting, the identification of a cystic lesion in the sella turcica should raise the possibility of such an entity in the clinical and radiological differential diagnosis. The current series provides further evidence that xanthomatous hypophysitis predominantly occurs as a secondary reaction to a ruptured Rathke's cleft cyst; thus, it is best classified as a secondary (reactive) hypophysitis.

Remon J, Le Rhun E, Besse B
Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era.
Cancer Treat Rev. 2017; 53:128-137 [PubMed] Related Publications
Leptomeningeal metastasis is a fatal manifestation seen in advanced cancer patients. Its incidence is increasing, reaching 3.8% in molecularly unselected non-small cell lung cancer patients and up to 5% and 9% in ALK-rearranged and EGFR-mutant lung cancer patients, respectively. The prognosis remains poor despite systemic treatment, intrathecal chemotherapy, radiation therapy and personalized treatments in molecularly selected patients. However, new therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease. Systemic chemotherapy, which may be combined with intrathecal chemotherapy, remains standard treatment for lung cancer patients with leptomeningeal disease and a good-risk profile. We summarize evidence reported in the literature for managing this complication in lung cancer patients. Based on this, we have selected potential therapeutic strategies that could be used in daily clinical practice.

Song YJ, Chen MT, Lian W, et al.
Surgical treatment for male prolactinoma: A retrospective study of 184 cases.
Medicine (Baltimore). 2017; 96(2):e5833 [PubMed] Free Access to Full Article Related Publications
A total of 184 cases of surgically treated male prolactinoma were analyzed retrospectively to summarize the outcome of this surgical intervention. We analyzed the general characteristics, clinical manifestations, hormone levels, imaging features, preoperative treatments, surgical outcomes, pathology results, and follow-up records for all included patients. The most common clinical manifestations included sexual dysfunction (47.4%), headache (55.9%), and visual disturbance (46.7%). Serum prolactin levels ranged from 150 to 204,952 ng/mL. Tumor size varied from 6 to 70 mm. Pituitary adenomas grew in a parasellar pattern with visual deficits occurring 40.7% of the time. After surgical therapy, 88.6% of patients achieved symptom relief, and 98.4% experienced an immediate postoperative decline in prolactin level. Fifty-seven patients (31.0%) achieved initial remission, and 26 patients (45.6%) experienced recurrence. Hence, our results suggest that in male prolactinoma characterized by a large pituitary diameter and high serum prolactin level, tumor size predicts the degree of gross resection. The prognostic predictors included preoperative tumor growth pattern and Ki-67 index.Citation: Yi-jun S, Mei-ting C, Wei L, Bing X, Yong Y, Ming F, Ren-zhi W. (2016) Surgical treatment for male prolactinoma: a retrospective study of 184 cases.

Mezzomo LC, Pesce FG, Marçal JM, et al.
Decreased TAp63 and ΔNp63 mRNA Levels in Most Human Pituitary Adenomas Are Correlated with Notch3/Jagged1 Relative Expression.
Endocr Pathol. 2017; 28(1):13-21 [PubMed] Related Publications
Despite recent advances in molecular genetics, the pituitary adenoma initiation, development, progress, and the molecular basis of their unique features are still poorly understood. In this sense, it is proposed that stem cell could be involved in pituitary adenoma tumorigenesis. It is suggested that TP63 has important functions in stem cells, and it may have interplay of TP63 and Notch and its ligand Jagged in this process. This study aimed to evaluate the distinct expression of TP63 isoforms (TAp63 and ΔNp63), as well as its correlation with Notch3 receptor and its ligand Jagged1 in human pituitary adenomas at the messenger RNA (mRNA) level. We included 77 pituitary adenoma tumor samples from patients who underwent surgical resection. The expression levels of TP63 isoforms (TAp63 and ΔNp63) and Notch3 and its ligand Jagged1 were evaluated by qRT-PCR using isoform-specific primers. We also evaluated proliferation index immunohistochemically using KI-67 antibody. The expression levels were associated with clinical outcomes, as age, gender, tumor size, and tumor subtype. In summary, we found that mRNA expression of both TP63 isoforms decreased in pituitary adenomas compared with normal pituitary control. On the other hand, there was an increase of relative Notch3 and Jagged1 mRNA expression in the majority of examined samples. The mRNA expression of three genes evaluated was correlated and statistically significantly. There was no significant association between gene expression and the analyzed clinical data. The current study has provided the first time evidence that Tap63 and ΔNp63 isoforms are underexpressed in most pituitary adenomas. These results are correlated with Notch3 and its ligand Jagged1 overexpression, corroborating previous studies pointing its antagonistic interactions.

Tan TS, Patel L, Gopal-Kothandapani JS, et al.
The neuroendocrine sequelae of paediatric craniopharyngioma: a 40-year meta-data analysis of 185 cases from three UK centres.
Eur J Endocrinol. 2017; 176(3):359-369 [PubMed] Related Publications
OBJECTIVES: The management of paediatric craniopharyngiomas was traditionally complete resection (CR), with better reported tumour control compared to that by partial resection (PR) or limited surgery (LS). The subsequent shift towards hypothalamic sparing, conservative surgery with adjuvant radiotherapy (RT) to any residual tumour aimed at reducing neuroendocrine morbidity, has not been systematically studied. Hence, we reviewed the sequelae of differing management strategies in paediatric craniopharyngioma across three UK tertiary centres over four decades.
METHODS: Meta-data was retrospectively reviewed over two periods before (1973-2000 (Group A: n = 100)) and after (1998-2011 (Group B: n = 85)) the introduction of the conservative strategy at each centre.
RESULTS: Patients had CR (A: 34% and B: 19%), PR (A: 48% and B: 46%) or LS (A: 16% and B: 34%), with trends reflecting the change in surgical approach over time. Overall recurrence rates between the two periods did not change (A: 38% vs B: 32%). More patients received RT in B than A, but recurrence rates were similar: for A, 28% patients received RT with 9 recurrences (32%); for B, 62% received RT with 14 recurrences (26%). However, rates of diabetes insipidus (P = 0.04), gonadotrophin deficiency (P < 0.001) and panhypopituitarism (P = 0.001) were lower in B than those in A. In contrast, post-operative obesity (BMI SDS >+2.0) (P = 0.4) and hypothalamic (P = 0.1) and visual (P = 0.3) morbidity rates were unchanged.
CONCLUSION: The shift towards more conservative surgery has reduced the prevalence of hormone deficiencies, including diabetes insipidus, which can be life threatening. However, it has not been associated with reduced hypothalamic and visual morbidities, which remain a significant challenge. More effective targeted therapies are necessary to improve outcomes.

Eroukhmanoff J, Tejedor I, Potorac I, et al.
MRI follow-up is unnecessary in patients with macroprolactinomas and long-term normal prolactin levels on dopamine agonist treatment.
Eur J Endocrinol. 2017; 176(3):323-328 [PubMed] Related Publications
OBJECTIVE: Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first-line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once prolactin is controlled. The aim of our study was to determine whether a regular MRI follow-up was necessary in patients with long-term normal prolactin levels under DA.
PATIENTS AND METHODS: We conducted a retrospective multicenter study (Marseille, Paris La Pitie Salpetriere and Nancy, France; Liege, Belgium) including patients with macroprolactinomas (largest diameter: >10 mm and baseline prolactin level: >100 ng/mL) treated by dopamine agonists, and regularly followed (pituitary MRI and prolactin levels) during at least 48 months once normal prolactin level was obtained.
RESULTS: In total, 115 patients were included (63 men and 52 women; mean age at diagnosis: 36.3 years). Mean baseline prolactin level was 2224 ± 6839 ng/mL. No significant increase of tumor volume was observed during the follow-up. Of the 21 patients (18%) who presented asymptomatic hemorrhagic changes of the macroprolactinoma on MRI, 2 had a tumor increase (2 and 7 mm in the largest size). Both were treated by cabergoline (1 mg/week) with normal prolactin levels obtained for 6 and 24 months. For both patients, no further growth was observed on MRI during follow-up at the same dose of cabergoline.
CONCLUSION: No significant increase of tumor size was observed in our patients with controlled prolactin levels on DA. MRI follow-up thus appears unnecessary in patients with biologically controlled macroprolactinomas.

Li CZ, Li CC, Hsieh CC, et al.
Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor: A case report.
Medicine (Baltimore). 2017; 96(1):e5774 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery.
METHODS AND RESULT: A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later.
CONCLUSION: If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

Xu W, Zhao J, Zhu Y, Zhang W
Cerebroretinal microangiopathy with calcifications and cysts: A case report.
Medicine (Baltimore). 2017; 96(1):e5545 [PubMed] Free Access to Full Article Related Publications
RATIONAL: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is believed to be an autosomal recessive genetic disease, with disorders in multisystem organs. Its characteristic neurological disorders manifested on neuroimaging are a triad of leukoencephalopathy, intracranial calcifications, and parenchymal cysts. In this paper, we report a CRMCC patient with multisystem involvement, focusing on the neuroimaging features, to get a better understanding of the rare disease and improve our diagnostic ability.
PATIENT CONCERNS: The 23-year-old female patient firstly presented with an adolescence onset of ophthalmological manifestations. Four years later, hematological and neurological disorders occurred, the latter of which demonstrated a relatively slow progression in the following 7 years preceding her presentation to our hospital.
INTERVENTIONS: During hospitalization, disorders involving digestive, cardiovascular and respiratory systems were also detected. In addition, a more comprehensive depiction of neurological disorders on neuroimaging was also obtained.
DIAGNOSES: On the basis of multiple system disorders and the detection of mutations in conserved telomere maintenance component 1(CTC1) gene, a diagnosis of CRMCC was made.
OUTCOMES: After supportive therapy during her 4-week hospitalization, the patient's general condition improved and was released from the hospital.
LESSONS: CRMCC could be primarily diagnosed with the aid of its multiple system disorders and remarkable neuroimaging features. Cerebral micro hemorrhages determined by the combination of CT and T2-weighted magnetic resonance images in our case could provide some additional information for diagnosis. Furthermore, several other associated disorders were depicted for the first time in our case, expanding the clinical spectrum of CRMCC.

Uchida H, Hirano H, Moinuddin FM, et al.
Radiologic and histologic features of the T2 hyperintensity rim of meningiomas on magnetic resonance images.
Neuroradiol J. 2017; 30(1):48-56 [PubMed] Related Publications
A hyperintensity rim is often seen at the brain-tumor interface of meningiomas upon T2-weighted (T2WI) magnetic resonance imaging (MRI), and it is referred to as the cerebrospinal fluid (CSF) space; however, the true nature of the rim remains unclear. We surveyed the MRI findings and the histopathologic characteristics of such rims. Our study population consisted of 53 consecutive patients who underwent meningioma removal at our hospital. The intensity of the rim on MRI scans obtained with different imaging sequences was assessed in all patients. We used 22 tumors for histopathologic investigation: tissue samples were acquired from both the tumor surface and from a deep intratumoral site. Of the 53 meningiomas, 37 (69.8%) manifested a hyperintensity rim on T2WI (T2-rim). The other 16 showed neither a hyperintense nor a hypointense rim on their T2WI. An enhancement effect corresponding to the rim was observed in 28 of the 37 (75.7%) T2-rim positive tumors. While 9 among the 37 tumors with a T2-rim (24.3%) did not show rim enhancement, they showed low intensity on fluid-attenuated inversion recovery (FLAIR) images. The microvascular density in the tumor capsule was significantly greater in the 12 T2-rim and rim enhancement positive tumors than in 10 tumors that were T2-rim negative or T2-rim positive, but rim enhancement-negative ( p < 0.001, Mann-Whitney U test). We found that 75.7% of T2 hyperintense rims that were detected at the brain-meningioma interface reflected a microvascular-rich capsule layer, rather than the CSF space.

Chan M, Hsiao E
Neurosarcoidosis on FET and FDG PET/CT.
Clin Nucl Med. 2017; 42(3):197-199 [PubMed] Related Publications
O-(2-fluoroethyl)-L-tyrosine (FET) PET/CT is a promising imaging modality for brain tumor imaging because of its reported high sensitivity for biologically active tumor tissue. We present a case of biopsy-proven neurosarcoidosis showing FET uptake. It is an important cause of false-positive uptake on FET PET/CT.

Elder BD, Ishida W, Goodwin CR, et al.
Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis.
Neurosurg Focus. 2017; 42(1):E16 [PubMed] Related Publications
OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I(2) values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I(2) = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

Monserrate A, Zussman B, Ozpinar A, et al.
Stereotactic radiosurgery for intradural spine tumors using cone-beam CT image guidance.
Neurosurg Focus. 2017; 42(1):E11 [PubMed] Related Publications
OBJECTIVE Cone-beam CT (CBCT) image guidance technology has been widely adopted for spine radiosurgery delivery. There is relatively little experience with spine radiosurgery for intradural tumors using CBCT image guidance. This study prospectively evaluated a series of intradural spine tumors treated with radiosurgery. Patient setup accuracy for spine radiosurgery delivery using CBCT image guidance for intradural spine tumors was determined. METHODS Eighty-two patients with intradural tumors were treated and prospectively evaluated. The positioning deviations of the spine radiosurgery treatments in patients were recorded. Radiosurgery was delivered using a linear accelerator with a beam modulator and CBCT image guidance combined with a robotic couch that allows positioning correction in 3 translational and 3 rotational directions. To measure patient movement, 3 quality assurance CBCTs were performed and recorded in 30 patients: before, halfway, and after the radiosurgery treatment. The positioning data and fused images of planning CT and CBCT from the treatments were analyzed to determine intrafraction patient movements. From each of 3 CBCTs, 3 translational and 3 rotational coordinates were obtained. RESULTS The radiosurgery procedure was successfully completed for all patients. Lesion locations included cervical (22), thoracic (17), lumbar (38), and sacral (5). Tumor histologies included schwannoma (27), neurofibromas (18), meningioma (16), hemangioblastoma (8), and ependymoma (5). The mean prescription dose was 17 Gy (range 12-27 Gy) delivered in 1-3 fractions. At the halfway point of the radiation, the translational variations and standard deviations were 0.4 ± 0.5, 0.5 ± 0.8, and 0.4 ± 0.5 mm in the lateral (x), longitudinal (y), and anteroposterior (z) directions, respectively. Similarly, the variations immediately after treatment were 0.5 ± 0.4, 0.5 ± 0.6, and 0.6 ± 0.5 mm along x, y, and z directions, respectively. The mean rotational angles were 0.3° ± 0.4°, 0.3° ± 0.4°, and 0.3° ± 0.4° along yaw, roll, and pitch, respectively, at the halfway point and 0.5° ± 0.5°, 0.4° ± 0.5°, and 0.2° ± 0.3° immediately after treatment. CONCLUSIONS Radiosurgery offers an alternative treatment option for intradural spine tumors in patients who may not be optimal candidates for open surgery. CBCT image guidance for patient setup for spine radiosurgery is accurate and successful in patients with intradural tumors.

Jia ZZ, Shi W, Shi JL, et al.
Comparison between perfusion computed tomography and dynamic contrast-enhanced magnetic resonance imaging in assessing glioblastoma microvasculature.
Eur J Radiol. 2017; 87:120-124 [PubMed] Related Publications
PURPOSE: Perfusion computed tomography (PCT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provide independent measurements of biomarkers related to tumor perfusion. The aim of this study was to compare the two techniques in assessing glioblastoma microvasculature.
MATERIALS AND METHODS: Twenty-five patients diagnosed with glioblastoma (14 males and 11 females; 51±11years old, ranging from 33 to 70 years) were includede in this prospective study. All patients underwent both PCT and DCE-MRI. Imaging was performed on a 256-slice CT scanner and a 3-T MRI system. PCT yielded permeability surface-area product (PS) using deconvolution physiological models; meanwhile, DCE-MRI determined volume transfer constant (K(trans)) using the Tofts-Kermode compartment model. All cases were submitted to surgical intervention, and CD105-microvascular density (CD105-MVD) was measured in each glioblastoma specimen. Then, Spearman's correlation coefficients and Bland-Altman plots were obtained for PS, K(trans) and CD105-MVD. P<0.05 was considered statistically significant.
RESULTS: Tumor PS and K(trans) values were correlated with CD105-MVD (r=0.644, P<0.001; r=0.683, P<0.001). In addition, PS was correlated with K(trans) in glioblastoma (r=0.931, P<0.001). Finally, Bland-Altman plots showed no significant differences between PS and K(trans) (P=0.063).
CONCLUSION: PCT and DCE-MRI measurements of glioblastoma perfusion biomarkers have similar results, suggesting that both techniques may have comparable utility. Therefore, PCT may serve as an alternative modality to DCE-MRI for the in vivo evaluation of glioblastoma microvasculature.

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