Strategies increasing the effectiveness of temozolomide at various levels of anti-GBL therapy.

Glioblastoma (GBL) is the most common (60-70% of primary brain tumours) and the most malignant of the glial tumours. Although current therapies remain palliative, they have been proven to prolong overall survival. Within an optimal treatment regimen (incl. surgical resection, radiation therapy, and chemotherapy) temozolomide as the current anti-GBL first-line chemotherapeutic has increased the median overall survival to 14-15 months, and the percentage of patients alive at two years has been reported to rise from 10.4% to 26.5%. Though, the effectiveness of temozolomide chemotherapy is limited by the serious systemic, dose-related side effects. Therefore, the ponderation regarding novel treatment methods along with innovative formulations is crucial to emerging the therapeutic potential of the widely used drug simultaneously reducing the drawbacks of its use. Herein the complex temozolomide application restrictions present at different levels of therapy as well as, the currently proposed strategies aimed at reducing those limitations are demonstrated. Approaches increasing the efficacy of anti-GBL treatment are addressed. Our paper is focused on the most recent developments in the field of nano/biomaterials-based systems for temozolomide delivery and their functionalization towards more effective blood-brain-barrier crossing and/or tumour targeting. Appropriate designing accounting for the physical and chemical features of formulations along with distinct routes of administration is also discussed. In addition, considering the multiple resistance mechanisms, the molecular heterogeneity and the evolution of tumour the purposely selected delivery methods, the combined therapeutic approaches and specifically focused on GBL cells therapies are reviewed.

Endoscopic treatment of cystic craniopharyngiomas in elderly patients. Report of three cases with a review.

Craniopharyngiomas are rare tumors with peak incidence between 5-14 and between 65-74 years of age. Treatment of choice is surgical resection, sometimes associated with radiation therapy. Complete tumor resection may be challenging. Radical surgery is particularly risky in older patients. Authors evaluate three cases of large cystic craniopharyngioma in patients in their 7th and 8th decade of life operated with the use of endoscopic technique. The postoperative follow-up period in which out- patient controls with imaging examinations were performed was up to 6 years. Symptoms of intracranial hypertension resolved in all patients in the immediate postoperative period. Visual acuity improved in two patients. No cases of aseptic meningitis have been reported. One patient underwent subsequent radio- therapy. The well-being of the operated patients continued. Endoscopic transventricular approach to cystic craniopharyngiomas may be a safe and effective approach in older patients, being an alternative to microsurgical procedures.

Retrospective evaluation of endoscopic treatment in colloid cyst of the third ventricle.

INTRODUCTION: Endoscopic methods have gained a well-established position in surgical treatment of colloid cysts of third ventricle. However, the possibility of total tumor removal with this method and the long-term effectiveness of treatment are being questioned. AIM: Personal twenty years' experience in treatment of third ventricle colloid cysts is presented on the basis of retrospective analysis. MATERIAL AND METHODS: The study group included 58 patients diagnosed by neuroimaging (head CT/MRI) with third ventricle colloid cyst. Post-hospital follow-up ranged from 18 to 42 months. Long-term follow-up head CT/MRI was performed in 39 patients. RESULTS: The colloid cyst was removed totally in 47 (81%) patients. In 11 cases, the colloid cyst's wall was tightly adherent to the roof of the third ventricle, which limited the radicality of the procedure. Sixteen patients demonstrated memory impairments, 4 patients epilepsy and another 2 akinetic mutism in the direct postoperative course. One patient died as a result of complications unrelated to the procedure. The average hospitalization was 5 days. In the late period after surgery, remission of the most, previously, reported ailments and symptoms has been reported. Surgical treatment for hydrocephalus was needed in 7 patients. In 3 cases cyst recurrence was diagnosed which required reoperation. CONCLUSIONS: The endoscopic methods allow the total removal of a third ventricle colloid cyst in most patients. Leaving a small coagulated fragment of the cyst rarely results in its recurrence. This method results in effective treatment with a low complications rate, shortens hospitalization time and brings the patient a high level of satisfaction with a quick recovery.

Elective Management of Unruptured Intracranial Aneurysms in Elderly Patients in a High-Volume Center.

BACKGROUND: The number of elderly patients with unruptured intracranial aneurysms is increasing with time in aging populations; however, the choice of the proper treatment method remains inconclusive. The goal of the study is to evaluate the possible complications and treatment outcome among elderly patients with unruptured intracranial aneurysm. METHODS: We analyzed 139 patients >65 years old, hospitalized between 2007 and 2017 in the high-volume neurosurgical center and diagnosed with unruptured intracranial aneurysm. From their medical records, we obtained medical history and aneurysm characteristics. Patients functional status was measured by modified Rankin Scale score on admission and at discharge. RESULTS: Seventy-two patients (55.97%) underwent aneurysm clipping and 39 (27.04%) coiling. Eighteen patients (11.90%) required stent assisted coiling and 4 (5.00%) had a single stent placement. A total of 133 patients (95.71%) had good treatment outcomes (modified Rankin Scale score 0-3, surgical 0.32 ± 1.03 vs. endovascular group 0.40 ± 1.12, P = 0.65). Complete or near-complete occlusion in the endovascular group was achieved in 83% directly after treatment and in 89% at 6-12 months after procedure. The microsurgical group presented 100% occlusion at follow-up. CONCLUSIONS: Despite the high prevalence of comorbidities in the age group >65 years old, the vast majority of patients in our series treated invasively for unruptured intracranial aneurysms presented with good treatment outcomes. Based on our results, among elderly patients, modern microsurgical as well as endovascular management of brain aneurysms in a high-volume center seems to be a safe and effective method of treatment.

Endoscopic biopsy of intra- and paraventricular brain tumors.

INTRODUCTION: Selection of the optimal treatment method of intra- and paraventricular tumors often requires histopathological verification that can be obtained by endoscopic biopsy. AIM: To discuss the usefulness of the method in their own experience. MATERIAL AND METHODS: The results of 32 biopsies carried out during a 15-year period were reviewed retrospectively. All tumors were located supratentorially, 25 of them were intraventricular and 7 paraventricular. In 18 patients the tumor was accompanied by internal hydrocephalus. If the ventricular system was narrow, the biopsy was supported by a neuronavigation system. A rigid neuroendoscope was used. The obtained material was subjected to intraoperative and final histopathological examination. RESULTS: Viable diagnostic material was obtained from all patients. In 11 patients with tumor of the posterior portion of the third ventricle, cerebrospinal fluid was collected additionally for diagnostic tests. In 9 patients with obstructive hydrocephalus concomitant third ventriculostomy was performed. In 4 patients with tumor of the interventricular foramen, the tumor mass was reduced and in 2 cases septostomy was performed. In 3 (9.4%) cases the histopathological diagnosis was descriptive and did not explain the nature of the lesion. Four biopsies resulted in persistent bleeding, in 3 patients transient memory impairments were observed, and in 1 patient an epileptic seizure occurred. Five patients needed ventriculoperitoneal shunt placement. CONCLUSIONS: Endoscopic biopsy is a safe method to verify the histopathological nature of intra- and paraventricular lesions. It enables sampling of cerebrospinal fluid, reduction of tumor size, and in cases of coexisting obstructive hydrocephalus also third ventriculostomy or septostomy.

The relation of pituitary adenomas invasiveness and the proliferative index measured by immunoexpression of topoisomerase IIα.

INTRODUCTION: Cavernous sinus invasion by pituitary adenoma affects surgical procedure radicality and consequently the postoperative course and prognosis in pituitary adenoma treatment. The search for pituitary adenoma aggressive behaviour markers is still a matter of debate. MATERIAL AND METHODS: This study evaluates the relation of pituitary adenoma invasiveness to the expression of topoisomerase IIα in 72 patients who underwent transsphenoidal pituitary surgery. The assessment of tumour growth was conducted according to the Hardy scale as modified by Wilson and the Knosp scale. Topoisomerase IIα expression in tumour specimens was evaluated using immunohistochemical staining. RESULTS: There was a correlation between the Knosp scale degree and the topoisomerase IIα expression (Spearman R = 0.3611, p < 0.005). The Kruskal-Wallis H test (p = 0.0034) showed that there was a statistically significant topoisomerase IIα expression increase in tumours classified as grade E on the Hardy scale. The topoisomerase IIα expression correlated also with tumour size (Spearman R = 0.4117, p < 0.001). Higher levels of expression were observed in macroadenomas, as compared to microadenomas (p < 0.05, Mann-Whitney test). Topoisomerase IIα expression correlated with cavernous sinus invasion. CONCLUSIONS: The topoisomerase IIα expression correlated more with invasiveness than with extensiveness, which might make it an eminently useful marker in the assessment of aggressive pituitary adenoma behaviour.

The quantitative evaluation of the immunohistochemical expression of the pituitary adenomas.

BACKGROUND: The aim of this study was to evaluate morphometrically the pituitary adenomas immunoexpression. METHODS: The cases of 72 patients were analyzed, who underwent transsphenoidal surgery for pituitary adenomas. Subsequently, the immunohistochemical pituitary hormone panel was applied including alpha- subunit of the glycoprotein hormones. Immunohistochemical sections were analyzed quantitatively with the help of morphometric grid. The percentage rate of the immunoexpression was calculated separately for every single hormone. RESULTS: As a result, 22 monohormonal adenomas (30.56%), 21 plurihormonal adenomas (29.17%), 21 immunonegative adenomas (29.17%) and 8 unreliable cases (11.11%) were recognized. The immunopositivity for particular hormones was found as follows: PRL and GH (25% each), α-SU (22.22%), ACTH (13.89%), LH and FSH (12.5% each), and TSH (5.56%). An average percentage of immunoexpression in each positive staining groups occurred as follows: for PRL - 59.98%, for GH - 53.97%, for ACTH - 39.21%, for TSH - 25.05%, for LH - 37.3%, for FSH - 54.66%, for α-SU - 45.71. CONCLUSION: The morphometrical method utilizing the immunoexpression index introduced in this study provided a very precise recognition of pituitary adenomas pathology. This method may limit the subjectivity of a single researcher and enable better comparison of the studies. The plurihormonality is a common phenomenon, and immunohistochemical staining for all adenohypophyseal hormones is obligatory in order to classify pituitary adenomas correctly. The awareness of an operating neurosurgeon of the importance of meticulous collecting histopathological material, especially in microadenoma cases, has essential impact on further neuropathological evaluation and possibility of immunohistochemical staining.

Neuronavigation-guided endoscopy for intraventricular tumors in adult patients without hydrocephalus.

INTRODUCTION: Intraventricular endoscopic operations are usually undertaken in patients with an enlarged ventricular system that provides good access to the ventricles, proper anatomic orientation and safety of maneuvers within the ventricles. AIM: The preliminary assessment of the feasibility of endoscopic procedures in cases occurring without hydrocephalus. MATERIAL AND METHODS: Eleven patients with intraventricular tumor diagnosed in neuroimaging studies were included in the study. None of these cases was accompanied by hydrocephalus. Surgery was performed with a rigid neuroendoscope using a neuronavigation system. The purpose of the operation was tumor removal or histological verification. RESULTS: The colloid cyst of the third ventricle was removed in 5 patients. In 1 patient a glial-derived tumor adjacent to the interventricular foramen was partially resected. In 1 case a tumor of the lateral ventricle was totally removed, and in another case the resection of such a tumor was partial. In 2 cases, a biopsy of the tumor of the posterior portion of the third ventricle was undertaken, while in 1 case the biopsy was abandoned due to the risk of injury of structures surrounding interventricular foramen. There were no intraoperative or postoperative complications. None of the patients developed hydrocephalus in the long-term follow-up. The results of treatment in the study group did not differ from those obtained in patients operated on with hydrocephalus. CONCLUSIONS: The presence of hydrocephalus is not necessary to perform endoscopic surgery. However, in each case it should be preceded by a thorough analysis of the feasibility of the endoscopic procedure and should be supported by a neuronavigation system.

Endoscopic third ventriculostomy - effectiveness of the procedure for obstructive hydrocephalus with different etiology in adults.

INTRODUCTION: After a time of domination of shunt placement, endoscopic third ventriculostomy (ETV) has been increasingly applied in treatment of obstructive hydrocephalus. AIM: To assess the effectiveness of ETV in treatment of adults with three-ventricle hydrocephalus of different etiology. MATERIAL AND METHODS: Ninety-six patients with obstructive hydrocephalus were studied: 24 with primary aqueductal stenosis, 61 with brain tumor, and 2 with basilar tip aneurysm. In 9 patients the etiology of hydrocephalus remained undetermined. The assessment of treatment results was based on clinical and radiological criteria. RESULTS: Clinical improvement was observed in 74 (77.1%) patients, and radiological improvement in 52 (54.2%). One patient died. Follow-up of 24 patients with primary aqueductal stenosis has shown that in 20 (83.3%) of them clinical improvement has been stable, and in 14 (58.3%) radiological improvement has been observed. Two patients required shunt placement due to hydrocephalus recurrence 12-24 months after the ETV procedure. Among 9 patients with undefined hydrocephalus, 3 required shunt placement within 6 months after ETV (2 shunted previously). Endoscopic third ventriculostomy treatment in a patient with hydrocephalus caused by basilar tip aneurysm succeeded. The assessment of ETV effectiveness in oncological patients has been indirect in view of the underlying disease. CONCLUSIONS: The best results of ETV treatment have been demonstrated for patients with primary aqueductal stenosis. Ventricle size cannot determine the effectiveness of treatment as an individual requirement. Endoscopic third ventriculostomy is effective in previously shunted patients although the prediction of outcome should be cautious. Endoscopic third ventriculostomy enables preparation for further therapy and is palliative treatment in oncological patients with secondary hydrocephalus.

[The modern approach in surgical treatment of skull base tumors in experience of neurotraumatology Department, Jagiellonian University Collegium Medicum from years 2003-2006]. / Wielospecjalistyczne metody operacyjne w leczeniu guzów podstawy czaszki na podstawie materialu Kliniki Neurotraumatologii UJCM w latach 2003-2006.

AIM: The aim of this study was to evaluate the impact of modern methods in surgical treatment of skull base tumors (multidisciplinary operating teams, new methods of dura and bone defects repair) on extension of tumor resection considering complications rate. MATERIAL AND METHODS: The retrospective study for 26 patients of Neurotraumatology Department, Jagiellonian University Collegium Medicum was carried out. All of patients were operated due to skull base tumor in period 2003 - 2006. In our series 9 patients (34.62%) was admitted with recurrence of skull base pathology. The age average for the sample was 57.38 +/- 14.84 years. RESULTS: In 16 cases (61.54%) dura was involved in pathological process. Every time if dura resection was performed, the resulting defect was repaired with Tachocomb, tissue glue, artificial meninge, fascia lata femoris, pericranium. In case of bone infiltration (especially in anterior fossa of the skull), the resection was followed by the cranioplasty (Norian, cranioplast) - prevention of brain herniation, and opened during the operation sinuses were closed with use of temporal muscle and biomaterials. 15 patients (57.69%) were operated in mixed multidisciplinary teams (cooperation with Maxillofacial Surgery and Otorhinolaryngology Department). The resection of pathological mass was evaluated as completed in 69.23% (n=18) cases. The most common histopathological finding was neoplasm from meninges: 11 (42.31%) and epithelial neoplasm 7 (26.92%). CONCLUSIONS: The modern micro- and neurosurgical techniques, new reconstructive methods of dura and bone defects (biomaterials) and multidisciplinary operating teams (craniofacial approach) diminished limitations for extended resection of tumors in very complexed area that skull base is, by complications on accepted level. Typical for skull base tumors' treatment is varied histopathological nature of mass lesions, what in relation to grading of tumors still has the strongest impact on long term results of treatment.

[Influence of anticoagulants on the appearance of chronic subdural hematoma]. / Wplyw leków przeciwzakrzepowych na wystepowanie przewleklego krwiaka podtwardówkowego.

In recent years in the Department of Neurotraumatology in Cracow it has been noticed the frequent connection between appearance of chronic subdural hematoma (CSDH) and treatment by anticoagulant medications. The aim of this study is to draw attention to the problem of insufficient control of anticoagulants consumption, especially by patients treated for cardiovascular system diseases that increases the risk of bleeding and CSDH development. The paper is based on data from questionnaires that was sent to patients with CSDH, cured in the Department of Neurotraumatology form 2004 to 2005. Analyzed was the group of 51 patients with chronic subdural hematoma; 37 individuals (72.5%) confirmed taking acetylsalicylic acid in the period of 3 months before admission to the Department, 9 (17.6%) patients answered that they were taking low-molecular weight heparin. One patient (1.9%) was taking chronically derivative of cumarin. The authors would inform that anticoagulant treatment might favour increase of chronic subdural hematoma incidence. It's especially important, because the average life expectancy has been prolonged in Poland and there are more people taking acetylsalicylic acid. This can be an epidemiological problem in future.