[Patient-centered care. Improvement of communication between university medical centers and general practitioners for patients in neuro-oncology]. / Patientenzentrierte Versorgung. Verbesserung der Kommunikation zwischen Universitätsklinik und Hausärzten bei neuroonkologischen Patienten.

INTRODUCTION: Communication between university medical centers and general practitioners (GP) is becoming increasingly more important in supportive patient care. A survey among GPs was performed with the primary objective to assess their opinion on current workflow and communication between GPs and the university medical center. METHODS: The GPs were asked to score (grades 1-6) their opinion on the current interdisciplinary workflow in the care of patients with brain tumors, thereby rating communication between a university medical center in general and the neuro-oncology outpatient center in particular. RESULTS: Questionnaires were sent to1000 GPs and the response rate was 15 %. The mean scored evaluation of the university medical center in general was 2.62 and of the neuro-oncological outpatient clinic 2.28 (range 1-6). The most often mentioned issues to be improved were easier/early telephone information (44 %) and a constantly available contact person (49 %). Interestingly, > 60 % of the GPs indicated they would support web-based tumor boards for interdisciplinary and palliative neuro-oncological care. CONCLUSION: As interdisciplinary care for neuro-oncology patients is an essential part of therapy, improvement of communication between GPs and university medical centers is indispensable. Integrating currently available electronic platforms under data protection aspects into neuro-oncological palliative care could be an interesting tool in order to establish healthcare networks and could find acceptance with GPs.

Does size matter? Minimally invasive approach in pediatric neurosurgery--a review of 125 minimally invasive surgeries in children: clinical history and operative results.

OBJECTIVE: Surgery is an integral component and typically the first line of therapy for children with central nervous system tumors. Conventional aims of neurosurgery including tumor removal, management of hydrocephalus, and diagnostic sampling have been radically modified with innovative technologies such as navigational guidance, functional mapping, endoscopic surgery, second-look surgery, and physiologic imaging. The aim of the study was to investigate our operative results using minimally invasive technique in children. METHODS: Clinical features, surgical technique and results, length of hospital stay, and complications were reviewed retrospectively. Pre- and early postoperative MRI was evaluated for degree of surgical resection. Correlation of tumor localization, lengths of hospital stay as well as surgical techniques and clinical outcome with follow-up was investigated. RESULTS: One hundred ten patients underwent 125 tumor resections using minimally invasive approaches (image- and functional guided tailored keyhole approaches for supratentorial, retrosigmoidal, and suboccipital keyhole approaches for infratentorial lesions). Most tumors were located supratentorial (62.4 %). In 29.6 % of the cases, the surgery was performed endoscope-assisted or endoscope-controlled; neuronavigation was used in 45.6 % and ultrasound in 24 % of the cases. Astrocytomas were diagnosed in 26.4 % of cases, ependymomas in 9.6 %, and medulloblastomas in 14.4 %. Gross total resection was achieved in 60.8 %. The most common complication was CSF fistula (n = 9), and the occurrence was significantly higher in younger children (p = 0.0001) and infratentorial located tumors (p = 0.02). Surgery for posterior fossa lesions was associated with a longer hospital stay (p = 0.02) compared to surgery of supratentorial lesions. Mean follow-up was 29.7 months (range 0.3-79.1 months), and most of the children recovered during the further course of the follow-up (symptoms better or idem in 74.4 %). CONCLUSION: In conclusion, our study shows that it is possible to achieve surgical results in the pediatric population applying minimal invasive techniques comparable to those described in the literature.

Postsurgical screening for psychosocial disorders in neurooncological patients.

BACKGROUND: The diagnosis of a brain tumor can cause severe psychosocial distress, which can have a variety of negative consequences on patients' physical and mental well-being. The detection of psychosocial distress in daily clinical routine is difficult and subsequent referral to mental health professionals is rare. The aim of this study was to determine the incidence of psychological disorders of patients early postoperatively and to investigate both the Hornheide Screening Instrument (HSI) and Distress Thermometer (DT) as screening tools in neurooncological practice. METHODS: One hundred and thirty-four patients with brain tumors of different histology were postoperatively evaluated by the Distress Thermometer and Hornheide Screening Instrument. Additionally, correlation to gender, age, localization of the tumor, Karnofsky performance score and tumor entity were analyzed. RESULTS: After initial surgery 36 patients (26.9 %) showed pathologic results in the HSI and 50 patients (36.7 %) were severely distressed (DT Score≥6). Women had the highest rate of psychological disorders, followed by patients suffering from gliomas and meningiomas. Further highlighting the results of both tests, over 80 % of those patients who scored pathologically in both tests were in need of professional psychiatric help due to depression. CONCLUSION: Both the DT and HSI are suitable instruments for identifying patients in psychological distress after brain tumor surgery in neurooncological routine. Our results confirm that nearly one third of patients are unable to overcome the difficulties facing the diagnosis of a brain tumor in this early situation and should be supported by mental health professionals.

MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers.

The prognostic role of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had received radiotherapy with concomitant and adjuvant TMZ as an initial treatment. Median overall survival (OS) did not significantly differ between 19 patients with MGMT promoter methylated tumors when compared to 28 patients with unmethylated tumors (18.9 vs 15.0 months; p = 0.1054). In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer OS (21.0 vs 11.1 months, p = 0.0127), while no significant survival differences were detected in the other two subgroups. Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors in the entire patient cohort or any of the three subgroups. The first-line BCNU + TMZ group showed no significant difference in OS when compared to the first-line BCNU group (18.9 vs 14.7 months), but tended to have more therapy-related adverse effects (53% vs 24%, p = 0.105). In summary, MGMT promoter methylation showed a non-significant trend toward longer survival in our patient cohort. The combination of TMZ radiochemotherapy with local delivery of BCNU did not provide a significant survival benefit compared to local BCNU alone, but was associated with a higher rate of adverse effects. Owing to the small number of patients investigated, however, these findings would need to be corroborated in larger patient cohorts.

The combination of carmustine wafers and temozolomide for the treatment of malignant gliomas. A comprehensive review of the rationale and clinical experience.

Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the "Stupp protocol") or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy. In clinical practice, patients with malignant glioma treated with BCNU wafer often also receive adjuvant temozolomide. However, current treatment guidelines are unclear on whether and how these treatment practices can be combined, and no prospective phase 3 study has assessed the safety and efficacy of combining BCNU wafers with temozolomide and radiation in high-grade malignant glioma. The rationale for multimodal therapy comprising surgical resection with adjunct local BCNU wafers followed by radiotherapy and temozolomide is based on complementary and synergistic mechanisms of action between BCNU and temozolomide in preclinical studies; a shared primary resistance pathway, methylguanine-DNA methyltransferase (MGMT); and the opportunity to overcome resistance through MGMT depletion to boost cytotoxic activity. A comprehensive review of the literature identified 19 retrospective and prospective studies investigating the use of this multimodal strategy. Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile.

Toxicity and survival in primary glioblastoma patients treated with concomitant plus adjuvant temozolomide versus adjuvant temozolomide: results of a single-institution, retrospective, matched-pair analysis.

BACKGROUND: To compare survival and hematological toxicity rates between two postoperative therapy regimens in patients with primary glioblastoma (GBM), namely temozolomide (TMZ) concomitant to radiation, followed by adjuvant TMZ, versus adjuvant TMZ after radiation only. PATIENTS AND METHODS: A total of 191 patients with primary GBM were postoperatively treated with either radiation and concomitant TMZ, followed by adjuvant TMZ (Stupp protocol) (n = 154), or radiation followed by adjuvant TMZ (n = 37). The incidence of hematological adverse effects (AE) was recorded for all patients. From both treatment groups, 26 patients were matched according to age, Karnofsky performance scale (KPS) score, and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. RESULTS: Hematological AEs were mild in both unmatched groups, but were significantly more frequent in the concomitant plus adjuvant TMZ group (p < 0.001). Matched-pair analysis confirmed significantly more frequent hematological AEs in the concomitant and adjuvant group compared to the sequential (adjuvant) TMZ group (p = 0,012). Patients treated with concomitant plus adjuvant TMZ showed significantly longer progression-free survival (PFS) (10.6 versus 6.6 months; p = 0.014), but no prolonged overall survival (OS) (16.9 vs. 15.6 months; p = 0.717) compared to patients who received the sequential treatment regimen. CONCLUSION: In this retrospective study, the OS in patients with primary GBM treated with sequential TMZ following radiation appeared to be similar to that in patients treated with concomitant plus adjuvant TMZ. Given the significantly higher risk of hematological AE for concomitant treatment, the role of concomitant plus adjuvant TMZ use compared to sequential administration of TMZ, especially for patients with MGMT-unmethylated tumors, should be further evaluated.

Paraganglioma of the filum terminale: review and report of the first case analyzed by CGH.

OBJECTIVE: As a rare tumor paraganglioma of the filum terminale is of diagnostic challenge. A thorough review of all published cases most often reveals a benign course if complete surgically resection is achieved. We report on the first molecular cytogenetic analyses performed on filum termiale paragangliomas. CLINICAL PRESENTATION: A 52-year-old man suffered from low back pain for many years that gradually worsened and was aggravated by sitting and bending. The pain radiated dorsally into both legs. Magnetic resonance imaging (MRI) with and without Gd-DTPA revealed a 12 mm sized, intradural oval mass at the level of L3 with slightly increased T2-signal and a rim of low signal on T2-weighted sequences. The tumor enhanced remarkably after Gd-DTPA. INTERVENTION: The patient underwent a left sided hemilaminectomy of L3. Durotomy revealed a well-delineated, firm and highly vascularized reddish tumor. The proximal terminal filum entered the tumor at the proximal pole and exited its distal pole. Coagulation and dissection of the terminal filum allowed in toto removal of the tumor. DNA was isolated from the formalin-fixed and paraffin-embedded specimen. The tumor was analyzed by comparative genomic hybridization, providing a normal DNA profile without any chromosomal copy number changes. CONCLUSION: The origin of paragangliomas of the CNS and especially of the filum terminale is still unclear. If no complete surgical resection can be achieved, molecular cytogenetic analysis is of additional value to prognostification of paragangliomas of the filum terminale.

Frontal sinus osteoma complicated by extended intracranial mucocele and cerebral abscess: neurosurgical strategy of a rare clinical entity.

The combination of paranasal sinus osteoma, mucocele and brain abscess is rare. Only one other case has been reported so far, where the cerebral abscess was diagnosed intraoperatively. We report here on a second patient with combined frontal sinus osteoma, intracerebral mucocele as well as cerebral abscess. However, in our case, the diagnosis of cerebral abscess was reached prior to surgery, which allowed for a tailored treatment strategy with abscess puncture under neuronavigational guidance and, after 3 weeks of antibiotic therapy with documented abscess shrinkage, osteoma and mucocele resection as well as reconstruction of the eroded dura.

A radiologic score to distinguish autoimmune hypophysitis from nonsecreting pituitary adenoma preoperatively.

BACKGROUND AND PURPOSE: Autoimmune hypophysitis (AH) mimics the more common nonsecreting pituitary adenomas and can be diagnosed with certainty only histologically. Approximately 40% of patients with AH are still misdiagnosed as having pituitary macroadenoma and undergo unnecessary surgery. MR imaging is currently the best noninvasive diagnostic tool to differentiate AH from nonsecreting adenomas, though no single radiologic sign is diagnostically accurate. The purpose of this study was to develop a scoring system that summarizes numerous MR imaging signs to increase the probability of diagnosing AH before surgery. MATERIALS AND METHODS: This was a case-control study of 402 patients, which compared the presurgical pituitary MR imaging features of patients with nonsecreting pituitary adenoma and controls with AH. MR images were compared on the basis of 16 morphologic features besides sex, age, and relation to pregnancy. RESULTS: Only 2 of the 19 proposed features tested lacked prognostic value. When the other 17 predictors were analyzed jointly in a multiple logistic regression model, 8 (relation to pregnancy, pituitary mass volume and symmetry, signal intensity and signal intensity homogeneity after gadolinium administration, posterior pituitary bright spot presence, stalk size, and mucosal swelling) remained significant predictors of a correct classification. The diagnostic score had a global performance of 0.9917 and correctly classified 97% of the patients, with a sensitivity of 92%, a specificity of 99%, a positive predictive value of 97%, and a negative predictive value of 97% for the diagnosis of AH. CONCLUSIONS: This new radiologic score could be integrated into the management of patients with AH, who derive greater benefit from medical as opposed to surgical treatment.

Immunopathology of primary hypophysitis: implications for pathogenesis.

The etiology of primary hypophysitis is still not fully elucidated. Histologically, primary hypophysitis includes three different main subtypes: lymphocytic (LYH), granulomatous (GRH), and xanthomatous (XH) hypophysitis. Clinical and laboratory findings suggest an autoimmune basis in primary hypophysitis. Controversy still exists about the composition of the inflammatory infiltrate and the relevant immunopathogenic effector mechanisms. Therefore, 21 cases of primary hypophysitis of different subtypes were analyzed with respect to the expression of lymphocyte and macrophage antigens as well as MHC class I and II molecules of the inflammatory infiltrate and the resident pituitary acinar cells. Lymphocyte infiltration in LYH (n = 15), but also in GRH (n = 4) and XH (n = 2), mainly consisted of T cells, while B cells were rare. Independent from the histopathologic subtype, T cell subsets showed equal ratios of CD4+ to CD8+ T cells. Highest numbers of activated CD8+ T cells were observed in LYH presenting during pregnancy, surrounding or even infiltrating preserved pituitary acinar cells. Moreover, an increased rate of activated CD8+ T cells correlated with a shorter duration of clinical symptoms. In LYH, aberrant expression of MHC class II antigens as well as overexpression of MHC class I molecules on pituitary cells were observed. Independent of the histologic subtype, macrophages mostly expressed markers of chronic activation and showed MHC class II positivity. LYH, GRH, and XH, although heterogeneous in their histologic appearance and in age distribution, exhibit a similar if not identical immunohistologic profile. It is highly likely that direct T cell-mediated cytotoxicity through CD8+ T cells, with the initial help of CD4+ T cells, is pivotal in the pathogenesis of primary hypophysitis, implicating a target autoantigen expressed by pituitary cells.

Expression of tyrosine kinases FAK and Pyk2 in 331 human astrocytomas.

The progression of malignancy from astrocytomas to glioblastomas remains clinically as well as histopathologically unpredictable. The focal adhesion kinase (FAK) and the proline-rich tyrosine kinase (Pyk2) show a high expression in glioma cell lines and have an influence on increased cell proliferation and migration of glioma cells in vitro and in vivo. The aim of this study was to correlate the coexpression of FAK and Pyk2 to the WHO grade of malignancy in human astrocytomas. Immunohistochemical staining scores of FAK and Pyk2 were analyzed in 331 astrocytomas and correlated to each other and to the WHO grade. Significant coexpression of FAK and Pyk2 in astrocytomas was demonstrated. Pyk2 expression occurred much more frequently and with higher expression scores within the different WHO grades. Beyond this, a significant correlation between the WHO grade of malignancy of astrocytomas and the expression of FAK, as well as of Pyk2, was detected. This connection and the roles of these two tyrosine kinases in the progression of tumors should be confirmed by further studies.