Identification of thymosins ß4 and ß 10 in paediatric craniopharyngioma cystic fluid.

BACKGROUND: Adamantinomatous craniopharyngioma is the third most recurrent paediatric brain tumour. Although histologically benign, it behaves aggressively as a malignant tumour due to invasion of the hypothalamus and visual pathways. Surgery is still the first and almost the only mode of treatment, although serious damage can occur as a consequence of tumour localization. The proteomic characterization of the intracystic tumoural fluid could contribute to the comprehension of the tumorigenesis processes and to the development of therapeutic targets to reduce cyst volume, allowing less invasive surgery and/or delay of the radical resection of the tumour mass and the collateral serious effects. METHODS: Intracystic fluid was analysed by a LC-ESI-IT-MS top-down platform after acidification, deproteinization and chloroform liquid/liquid extraction. FINDINGS: Thymosin ß4 and ß10 peptides were for the first time identified in the intracystic fluid of adamantinomatous craniopharyngioma by low- and high-resolution MS analysis coupled with LC. The two peptides showed the same distribution trend in the analysed samples. Thymosin ß4 and ß10 were present in 77 % of the analysed samples. These peptides were not found in the cerebrospinal fluid available for two patients. INTERPRETATION: The presence of ß-thymosins in the intracystic fluid of the tumour confirmed the secretion of these proteins in the extracellular environment. Due to their G-actin-sequestering activity and antiapoptotic and anti-inflammatory properties, these peptides could be strictly involved in both tumour progression and cyst development and growth.

Surgical outcome in 90 patients with craniopharyngioma: an evaluation of transsphenoidal surgery.

OBJECTIVE: To analyze surgical outcomes in 90 patients with craniopharyngioma treated by standard transsphenoidal surgery (TSS) or extended transsphenoidal surgery (eTSS). METHODS: From 1990-2008, 90 patients (64 adults and 26 children) underwent TSS for craniopharyngioma (34 subdiaphragmatic and 56 supradiaphragmatic). TSS was performed as the initial surgery in 62 patients and as the second procedure in 28 patients. RESULTS: Total tumor removal was achieved in 70 (77.8%) patients, subtotal removal was achieved in 17 (18.9%), and partial removal was achieved in 3 (3.3%). Total removal was more often accomplished in initial surgery (56 of 62 [90.3%]) than second surgery (14 of 28 [50.0%]). Postoperative deterioration of anterior pituitary hormones developed in 31 of 47 (66.0%) patients with preoperative normal function or partial anterior pituitary loss. New-onset postoperative diabetes insipidus (DI) developed in 35 of 67 (52.2%) patients. Of 61 patients with preoperative visual loss, 55 (90.2%) noted some degree of visual improvement after surgery. The early postoperative mortality rate was 2.2% (2 of 90 patients). Cerebrospinal fluid (CSF) leakage occurred in 11 patients (12.2%), and 5 patients required surgical repair of the leak. Tumor recurrence was observed in seven (7.8%) patients during a mean follow-up period of 4.6 years. CONCLUSIONS: Most craniopharyngiomas including the supradiaphragmatic type can be removed safely by TSS with a good outcome, although endocrine function frequently worsens after surgery. Dural fascia graft is a very effective technique to prevent CSF leaks, especially after eTSS.

Multiple intracranial seeding of craniopharyngioma after repeated surgery--case report.

A 17-year-old woman presented with a rare case of intracranial seeding of craniopharyngioma after repeated surgery. She initially presented with secondary amenorrhea and visual impairment. Magnetic resonance imaging revealed a suprasellar mass. Subtotal removal of the tumor was performed. The diagnosis was adamantinomatous craniopharyngioma. Seven months later, the patient underwent a second operation for recurrence of the craniopharyngioma. Subsequently, ventriculoperitoneal (VP) shunting and gamma knife surgery were performed. Twenty-seven months after the first operation, multiple cystic lesions were found in the right frontal and temporal lobes. Positive tumor cytology was observed in the cerebrospinal fluid obtained from the VP shunt chamber. These tumors were subtotally resected. However, the patient died from consecutive tumor recurrence 4 years after the initial diagnosis.

Immunoreactive human chorionic gonadotrophin from the cyst fluid and CSF of patients with craniopharyngioma.

A specific radioimmunoassay for the beta-chain of human chorionic gonadotrophin irHCG beta has demonstrated HCG-like material to be present in craniopharyngioma cyst fluid in nine consecutive patients with craniopharyngioma. There was no detectable LH/HCG bioactivity as assessed using testosterone production from isolated Leydig cells from rat testis in seven samples tested. One patient was also found to have measurable irHCG beta in the cerebrospinal fluid (CSF), which fell to undetectable levels following surgery; in this patient, there was clinical evidence that the cyst fluid had leaked into the CSF pre-operatively. Immunocytochemical staining for HCG beta and intact HCG was positive in five of the tumours. irHCG beta was not measurable in the serum of any of the patients.

Suprasellar arachnoid cysts: 2. Evaluation of CSF dynamics.

Suprasellar arachnoid cysts are an infrequent but surgically remediable cause of hydrocephalus and neurologic deficits. The optimal method of treatment varies according to whether the cyst communicates with the subarachnoid space; the presence or absence of associated hydrocephalus; and the exact site(s) and severity of intraventricular and extraventricular cerebrospinal fluid (CSF) obstruction. Eight patients with suprasellar arachnoid cysts are described to emphasize the importance of pretherapeutic investigation of CSF dynamics. The variability of the ventriculocisternal-cyst CSF dynamics and the value of metrizamide computed tomographic cisternography and ventriculography in investigation of the CSF pathways are stressed. A diagnostic approach to the evaluation of the CSF dynamics is outlined, based on whether hydrocephalic or compressive symptoms predominate.

Decreased cerebrospinal fluid glutamine levels in patients with benign brain tumors.

CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with noncerebral tumors, and a reference group of 24 patients. The mean +/- SD levels in the benign tumor group (424 +/- 124 microM) were significantly lower (p less than 0.0004) than those in the reference group (642 +/- 195 microM). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 +/- 210 microM) or noncerebral tumor group (599 +/- 127 microM) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter.

Concentrations of Ag, Al, Au, Bi, Cd, Cu, Pb, Sb, and Se in cerebrospinal fluid of patients with cerebral neoplasms.

We measured the concentrations of nine trace elements in cerebrospinal fluid of 11 patients with malignant brain tumors, 11 with benign brain tumors, and 10 control patients, using flameless atomic absorption spectrophotometry. The mean and standard deviation for these concentrations (microgram/L) in the control group were 5.1 +/- 2.9 (silver), 326.6 +/- 171.2 (aluminum), 38.5 +/- 32.2 (gold), 36.6 +/- 23.7 (bismuth), 1.5 +/- 1.3 (cadmium), 39.8 +/- 24.7 (copper), 15.7 +/- 11.5 (lead), 20.9 +/- 3.8 (antimony), and 19.1 +/- 13.3 (selenium). Concentrations of silver and lead were markedly increased in patients with malignant cerebral neoplasms. The malignant-tumor/control patient concentration ratios were 2.31 for silver and 2.11 for lead. We observed no significant differences between the results for the benign tumor patients and the control group.

Diagnostic pitfalls in cerebrospinal fluid cytology.

Four types of cells that may be the source of important diagnostic pitfalls in cerebrospinal fluid cytology are presented: (1) nucleus pulposus cells, (2) keratinized squamous cells from craniopharyngioma and sphenoid sinus carcinoma, (3) reactive leptomeningeal cells and (4) epitheloid cells from sarcoidosis. For each the cellular morphology is described and representative clinical, cytologic and histologic presentations are discussed.

Homovanillic acid and 5-hydroxyindoleacetic acid in the ventricular CSF of comatose patients with obstructive hydrocephalus.

Ventricular cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined every 2 to 4 hours over a period of 1 to 4 days in 12 patients, consisting of seven cases of brain tumor, two cases of cerebrovascular disease, and three cases of head injury. The concentrations of HVA and 5-HIAA varied with time in all cases, and significant correlations were found between the two values in eight cases. However, the relationship between variations of HVA and 5-HIAA levels and rhythms of sleep and waking could not be clarified. Both HVA and 5-HIAA concentrations varied at high levels in two patients whose CSF flow was completely blocked by tumor at the site of the fourth ventricle and aqueduct, respectively. On the contrary, in a case with craniopharyngioma in the third ventricle which blocked the bilateral foramina of Monro, although the HVA values were high, the 5-HIAA values varied at low levels. Of five comatose patients, two had cerebrovascular lesions and three had sustained head injury, and, in four of the five, the values of either one or both of HVA and 5-HIAA were low, but in the fifth case the 5-HIAA value was high. Estimation of HVA and 5-HIAA concentrations in ventricular CSF may be a valuable tool in the investigation of brain monoamine metabolism. However, many factors must be considered in the interpretation of results of clinical studies.

Distribution of beta2-microglobulin in cerebrospinal fluid and in cystic fluid of brain tumors. A preliminary study.

The concentrations of immuno-reactive beta2-microglobulin (beta2m) were measured in the cerebrospinal fluid (CSF) and the cystic fluid (CF) of Central Nervous System (CNS) tumours (gliomas, n = 5; craniopharyngiomas, n = 5) and in the culture medium of established cell lines derived from CNS tumors. These data are compared with plasma and CSF values of beta2m in normal subjects (n = 15) and in a group of peripheral solid tumors (metastatic breast carcinomas, n = 9). In the control group the absence of correlation between plasma and CSF values, suggests an independant production of beta2m in the two compartments considered. The capacity of CNS tumor cells to synthesize beta2m is demonstrated in vitro. In vitro beta-2m concentrations in the CF embryonic tumors (craniopharyngiomas) is significantly more elevated than in non malignant astrocytomas.

[Endocrinological evaluation of sellar and suprasellar tumor cases (the ninth report)--on the PRL levels in the CSF (author's transl)].

Prolactin (PRL) levels in the cerebrospinal fluid (CSF) and plasma of 25 patients with sellar and suprasellar tumors, i.e. 5 of PRL secreting adenoma, 5 of GH secreting adenoma, 7 of so-called non-functioning pituitary adenoma, 5 of tuberculum sellae meningioma and 3 of craniopharyngioma, were studied in relation to the size of suprasellar extension measured by our own method on pneumoencephalograms. Plasma and CSF samples were obtained simultaneously at the time of lumbar puncture for pneumoencephalography. 1) Five patients of PRL secreting adenoma, whose plasma PRL levels ranged from 530 to 4,000 ng/ml, showed high PRL levels over 50 ng/ml in the CSF. On the contrary, 20 patients of the other tumors, whose plasma PRL levels were lower than 30 ng/ml, showed low PRL levels in th4 CSF, being below the sensitivity limit in the majority. 2) In 3 out of 5 PRL secreting adenomas, the PRL level in the CSF was higher than the plasma level and they showed a fairly large extrasellar extension. However in the remaining 2 the PRL level in the CSF was lower than a tenth of that in the plasma, and these revealed relatively small suprasellar extension. From these facts the presence of PRL at a high level in the CSF seems to be specific in the PRL secreting adenomas, and there seems to be a relationship between the CSF-plasma ratio of PRL level and the extrasellar extension in these cases.