Surgery and perioperative management of patients with Cushing's disease.

Transsphenoidal surgery (TSS) is the initial treatment modality of first choice in Cushing's disease (CD). With microscopic TSS and endoscopic TSS, two operative techniques with equally favourable remission rates and operative morbidity are available. On average, remission is achieved with primary TSS in 80% of patients with microadenomas and 60% of patients with macroadenomas. The current literature indicates that remission rates in repeat TSS for microadenomas can also exceed 70%. Experience with TSS in CD plays an important role in the success rate and centralization in Pituitary Centres of Excellence has been proposed. Microadenoma stage, imaging-visible adenoma, confirmation of ACTH-positive adenoma on histopathology and noninvasiveness are positive predictors for postoperative remission. In postoperative management, a steroid-sparing protocol with early postoperative assessment of remission status is recommended. Convincing evidence suggests that prolonged postoperative prophylactic antithrombotic measures can significantly reduce the risk of postoperative thromboembolic events in CD. Prevention or successful treatment of cortisol withdrawal syndrome remains an unsolved issue that should be a focus of future research. The further development and broad availability of functional imaging hold promise for improved preoperative detection of microadenomas. Intraoperative identification of microadenomas by specific fluorescent targeting could be a promising future avenue for the treatment of patients with negative imaging.

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

CONTEXT: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. OBJECTIVE: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. METHODS: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. RESULTS: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. CONCLUSION: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

Corticotroph tumor progression after bilateral adrenalectomy (Nelson's syndrome): systematic review and expert consensus recommendations.

BACKGROUND: Corticotroph tumor progression (CTP) leading to Nelson's syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing's disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. METHODS: A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. RESULTS: Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). CONCLUSIONS: We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2-4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension.

Papillary tumor of the pineal region: a single-center experience.

Papillary tumor of the pineal region (PTPR) is a rare entity. Its clinical presentation is diverse, and establishing an accurate and timely diagnosis may be challenging. Treatment recommendations are based on the evidence level of case series. Recently, several key advances have been made for immunohistochemical characterization, molecular diagnostics, and neurosurgical treatment of PTPR. Here, we describe our single-center experience.

Clinical Situation, Therapy, and Follow-Up of Adult Craniopharyngioma.

CONTEXT: Craniopharyngioma is a rare neoplastic entity of the central nervous system. Childhood-onset craniopharyngioma is the subject of frequent research whereas the information on adult-onset craniopharyngioma is scarce. OBJECTIVE: The objective of this study was to examine the level of daily impairment in adult patients suffering from craniopharyngioma. DESIGN: Noninterventional patient registry indexed as PV4842 with the local ethics committee. SETTING: The study is set in a hospitalized and ambulatory setting. PATIENTS: 148 patients with adult-onset craniopharyngioma were recruited from 8 centers, 22 prospectively and 126 retrospectively. Mean follow-up was 31 months. INTERVENTIONS: No interventions performed. MAIN OUTCOME MEASURES: Complications, symptoms, body mass index (BMI), and quality of life (QoL; EORTC QLQ C30 and BN20) were recorded preoperatively and at follow-up. The hypotheses tested were generated after data collection. RESULTS: Complications were more frequent after transcranial than transsphenoidal approaches (31 % vs. 11%; P < 0.01). Preoperative obesity was present in 0% papillary and in 38% of all adamantinomatous craniopharyngiomas (P = 0.05), and diabetes insipidus was more frequent for papillary craniopharyngioma (36.8% vs. 16,7%; P < 0.05). Hormone deficits at follow-up were reduced in 16.9%, equal in 31.4%, and increased in 63.6% (P < 0.001). BMI increased from 28.7 ± 7.4 kg/m2 before surgery to 30.2 ± 7.4 kg/m2 at follow-up (P < 0.001). In QoL, a decrease of future uncertainty (62.5 vs. 36.8; P = 0.02) and visual disorders (38.9 vs. 12.0; P = 0.01) were observed in the prospective collective after surgery. CONCLUSIONS: Adult craniopharyngioma is associated with a complex sociological and psychological burden and hypothalamic dysfunction, warranting further investigation and emphasizing the need for a wider treatment approach.

Interoptic, Trans-lamina Terminalis, Opticocarotid Triangle, and Caroticosylvian Windows From Mini-Supraorbital, Frontomedial, and Pterional Perspectives: A Comparative Cadaver Study With Artificial Lesions.

Introduction: The mini-supraorbital (MSO) and pterional (PT) approaches have been compared in a number of studies focusing on the treatment of aneurysms, craniopharyngiomas, and meningiomas. The goal of this study was to analyze the surgical exposure to different artificial lesions through interoptic (IO), trans-lamina terminalis (TLT), opticocarotid triangle (OCT), and caroticosylvian (CS) windows from the MSO, frontomedial (FM), and PT perspectives. Methods: The MSO, PT, and FM approaches were performed sequentially in two fixed cadaver heads. Three colored spheres were placed around the optic chiasm: (1) between the optic nerves; (2) between the optic nerve and the internal carotid artery; and (3) between the internal carotid artery and the oculomotor nerve. The surgical exposures to these structures by using the IO, TLT, OCT, and CS windows were compared. Results: (1) IO window: from the MSO and PT approaches, the total surgical exposure mainly allows visualization of contralateral lesions. The FM approach was superior for exploration of both sides of the area between the optic nerves. (2) TLT pathway: the MSO and PT approaches mainly expose the contralateral third ventricle wall. (3) OCT window: the PT approach allows exposure of a larger part of the sphere between the optic nerve and the internal carotid artery than the MSO approach. (4) CS window: the PT approach allows a better exposure of lateral structures such as the oculomotor nerve and of the medial prepontine area in comparison to the MSO approach. Conclusion: Simulation of the surgical situation with artificial lesions is a good model for comparing surgical perspectives and for analyzing feasibility of lesion exposure and resection.

Quantification of specific growth patterns and frequency of the empty sella phenomenon in growth hormone-secreting pituitary adenomas.

PURPOSE: To assess and quantify the prevalence and co-occurence of a sellar floor lowering and empty sella phenomenon in patients with GH (growth hormone)-secreting pituitary adenoma. METHODS: A total number of 159 acromegalic patients were included in this study, as well as two control groups (150 patients with non-GH-secreting adenomas and 50 patients without pituitary adenomas). Magnetic resonance images of all patients were evaluated for presence of an empty sella, downward and lateral tumor extension, and maximum superoinferior diameter of the mass. Additionally, these values were correlated with growth hormone and IGF-1 levels. RESULTS: The empty sella phenomenon was detected significantly more often in patients with a GH-secreting adenoma with a prevalence of 22% vs. 5.3% in non-GH-secreting adenomas (p < 0.001) or 8% in the healthy control group (p = .036). Moreover, GH-secreting adenomas presented with a significant rate of downward tumor extension (74.8% vs. 35.5%; p < 0.001), whose extent correlated inversely but weakly with the GH hormone level (r = - 0.17; p = .036). It was also found that a decreased superoinferior diameter and higher ratio of intrasellar to suprasellar extension are predictive quantitative values for the presence of a GH-secreting adenoma (area under curve, 0.712). CONCLUSIONS: GH-secreting pituitary adenomas are frequently associated with an empty sella phenomenon. Moreover, GH-secreting adenomas are frequently accompanied by an enhanced, quantitatively measurable impression of the sellar floor. Hypothetically, this is caused by tumor-induced local bone remodeling processes.

Validation of the Tuebingen CD-25 Inventory as a Measure of Postoperative Health-Related Quality of Life in Patients Treated for Cushing's Disease.

BACKGROUND: To evaluate the construct and criterion validity of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25) for application in patients treated for Cushing's disease (CD). METHODS: A total of 176 patients with adrenocorticotropin hormone-dependent CD (144 of them female, overall mean age 46.1 ± 13.7 years) treated at 3 large tertiary referral centers in Germany were studied. Construct validity was assessed by hypothesis testing (self-perceived symptom reduction assessment) and contrasted groups (patients with vs. without hypercorticolism). For this purpose, already existing data from 55 CD patients was used, representing the hypercortisolemic group. Criterion validity (concurrent validity) was assessed in relation to the Cushing's quality of life questionnaire (CushingQoL), the Short Form 36 health survey (SF-36), and the body mass index (BMI). RESULTS: Patients with self-perceived remarkable symptom reduction had significant lower Tuebingen CD-25 scores (i.e. better health-related quality of life) than patients with self-perceived insufficient symptom reduction (p < 0.05). Similarly, the mean scores of the Tuebingen CD-25 scales were lower in patients without hypercortisolism (total score 27.0 ± 17.2) compared to those with hypercortisolism (total score 45.3 ± 22.1; each p < 0.05), providing evidence for construct validity. Criterion validity was confirmed by the correlations between the Tuebingen CD-25 total score and the CushingQoL (Spearman's coefficient -0.733), as well as all scales of the SF-36 (Spearman's coefficient between -0.447 and -0.700). CONCLUSION: The analyses presented in this large-sample study provide robust evidence for the construct and criterion validity of the Tuebingen CD-25.

Similar psychopathological profiles in female and male Cushing's disease patients after treatment but differences in the pathogenesis of symptoms.

BACKGROUND: Female Cushing's disease (CD) patients with active disease present more frequently with depression compared to their male co-sufferers. This study investigated whether the gender difference prevails after remission and whether gender-specific factors contributing to mental health exist. METHODS: 72 biochemically cured CD patients (11 male, mean age 45.9 ± 13.7 years) who underwent transsphenoidal tumour removal filled out the Symptom Checklist-90-Revised inventory on average 42.1 ± 32.9 months after surgery. Multiple regression analyses included the following independent factors: (i) age, (ii) presence of comorbidities, (iii) presence of hypocortisolism, (iv) presence of hypopituitarism, (v) disease duration until diagnosis, (vi) time elapsed since surgery, and (vii) postoperative radiotherapy to predict postoperative psychopathology. RESULTS: Regarding the Global Severity Index, 23.0% of the female and 27.3% of the male CD patients presented with abnormal scores. In all nine dimensions, psychopathological abnormalities were present in both female and male patients with the same frequency and intensity (each p > 0.05). Prolonged time to diagnosis was a strong predictive factor for worse psychopathological status only in male patients. Among female patients, only the presence of comorbidities and to some extent pituitary deficiencies were related to psychopathological status. CONCLUSIONS: During the remission phase of CD, female and male patients present with similar psychopathological profiles. In males, long-term biochemical effects of previous hypercortisolism seem to be salient for psychopathology. In contrast, in females, the presence of comorbidities/stressors they have to cope with is the predictive factor for psychopathology. The results underline gender differences in CD and the need to separate them on various issues.

Prognostic relevance of global histone 3 lysine 9 acetylation in ependymal tumors.

OBJECT: Ependymal tumors are highly variable in clinical and molecular behavior and affect both children and adults. Regarding the paucity of appropriate experimental models, the underlying molecular mechanisms of their behavioral variability are poorly understood. Considering the increasing evidence of epigenetic changes in various tumors, in addition to the preclinical success of epigenetic-based therapeutics in tumors of the CNS, epigenetic study of ependymal tumors is warranted. METHODS: Using immunohistochemistry, the authors investigated the patterns of global acetylation of lysine position 9 of histone 3 (H3K9Ac), an epigenetic marker of active gene transcription, in 85 ependymal tumors with various WHO grades and clinicopathological characteristics. RESULTS: Most of the nuclei in all ependymal tumors were H3K9Ac negative (mean ± SD 65.9% ± 26.5 vs 34.1% ± 26.5% positive, p < 0.0001). Subependymomas had more H3K9Ac-positive nuclei (67.2% ± 10.2%) than myxopapillary ependymomas, ependymomas, and anaplastic ependymomas (p < 0.05). Additionally, intracranial parenchymal tumors had significantly fewer H3K9Ac-positive nuclei (13.1% ± 21.9%) than tumors of other CNS localizations (p < 0.001), and supratentorial ventricular tumors had the highest number of H3K9Ac-positive nuclei (66.4% ± 11.8%) among CNS ependymal tumors (p < 0.0001). The H3K9Ac pattern in ependymal tumors also revealed prognostic significance such that tumors with less than 20% acetylated nuclei had a higher probability of recurrence than tumors with 20% or more acetylated nuclei (p = 0.0327), and recurrent tumors had significantly fewer H3K9Ac-positive nuclei than primary ones (16% ± 22.5% vs. 38% ± 25.8%; p < 0.0001). However, the effect of tumor location on survival of patients was nonsignificant in a multivariate survival analysis, and H3K9 acetylation levels of tumors contributed independently to the survival of patients. In addition, ependymal tumors with more than or equal to 20% H3K9 acetylated cells had lower MIB-1 expression than those with less than 20% H3K9 acetylated cells (p < 0.01). CONCLUSIONS: Global H3K9Ac contributes independently to the prognosis of patients with ependymal tumors such that tumors with lower H3K9Ac values have a higher probability of recurrence and are more proliferative. Additionally, subependymomas have a higher H3K9Ac profile than other ependymal tumor subclasses, underlining their benign clinical behavior.

Tuebingen CD-25 is a sensitive tool to investigate health-related quality of life in Cushing's disease patients in the course of the disease.

BACKGROUND: The primary object was to investigate whether the Tuebingen CD-25 captures changes in health-related quality of life (HRQoL) sensitively in Cushing's disease (CD) and to identify factors that favour postoperative HRQoL. METHODS: 17 CD patients were scheduled for transsphenoidal tumour removal and filled out the inventory before and after surgery. The mean time elapsed after surgery was 14.4 ± 11.3 months. All patients were in remission at the second timepoint of investigation. RESULTS: HRQoL as assessed with the Tuebingen CD-25 improved significantly after successful surgical tumour removal. A large effect size (Cohen's d = 0.84) in the total score indicates good sensitivity to change. 13 patients (76.5%) showed impaired HRQoL preoperatively compared with a general population sample. Postoperatively, 35.3% of the patients still suffered from an impaired HRQoL. Stepwise linear regression analysis revealed that less comorbidities (≤2) and greater morning cortisol decrease were promotive factors for better postoperative HRQoL (p < 0.05). The postoperative improvement in HRQoL could be best predicted by the presence of preoperative HRQoL impairment and age of the patients, i.e. patients who were younger were more likely to improve. Moreover, patients without postoperative pituitary deficiencies improved significantly more in the cognition scale. A tendency towards more improvement in overall HRQoL was observed in non-hypocortisolaemic patients. CONCLUSIONS: The Tuebingen CD-25 has proved to be a capable and sensitive instrument to investigate HRQoL in the course of disease. The number of postoperative comorbidities had the greatest impact on postoperative well-being.

Health-related quality of life and psychiatric symptoms improve effectively within a short time in patients surgically treated for pituitary tumors--a longitudinal study of 106 patients.

BACKGROUND: Reduced health-related quality of life (HRQoL) is a common complaint in patients suffering from pituitary tumors. Although successful tumor treatment has been reported to lead to an improvement in perceived HRQoL, the temporal gradient at which these improvements occur has not been fully addressed. METHODS: Using three validated health-related questionnaires (SF-36, SCL-90-R, QLS-H), we assessed HRQoL in 106 adult patients harboring pituitary tumors (mean age 48.0 ± 16.0 years) before as well as 3 and 12 months after initiation of treatment. The AcroQoL questionnaire was additionally applied in acromegalic patients. RESULTS: There was a significant improvement in all but one scale (role-physical) of the SF-36 questionnaire and all but two scales (interpersonal sensitivity, paranoid ideation) of the SCL-90-R, the QLS-H score and the AcroQoL subscales within 3 months after surgical treatment. The trend to amelioration continued at the 12 month re-assessment, but did not reach statistical significance. Linear regression analyses revealed that younger age and male gender favor a more distinct improvement of HRQoL after treatment. CONCLUSIONS: HRQoL is considerably reduced before treatment for pituitary disease. Improvement is an early postoperative phenomenon and occurs within 3 months after treatment. Men and younger patients are more likely to improve within this time span.

Osteonectin expression in surrounding stroma of craniopharyngiomas: association with recurrence rate and brain infiltration.

Craniopharyngioma is an epithelial tumor of the sellar region with a high survival rate but a high rate of recurrence, especially in children. Hypothalamic involvement, tumor recurrence, and multiple treatments result in clinical deterioration and impaired quality of life. Using immunohistochemistry, we investigated the expression pattern of osteonectin, a marker of tumor invasion and aggressive behavior, in 43 cases of craniopharyngioma. We observed a positive correlation of osteonectin expression in connective-type stromal tissue surrounding the epithelial tumor cells of craniopharyngioma with the extent of central nervous system infiltration and recurrence rate (P < .001). Given the previous success of chemotherapeutic agents that target the tumor microenvironment, our findings on osteonectin expression in stroma of craniopharyngiomas might, hopefully, be a guide to find newer prognostic markers capable of estimating the risk of progression or recurrence. They may also aid in the development of therapeutics that target tumor microenvironment to improve patient outcome.

Predictors for visual dysfunction in nonfunctioning pituitary adenomas - implications for neurosurgical management.

BACKGROUND: Despite ample experience with surgical treatment of nonfunctioning pituitary adenomas, objective data defining the risk for visual compromise depending on the suprasellar extension in pituitary adenomas are sparse. DESIGN AND PATIENTS: We measured the suprasellar extension of 98 newly diagnosed suprasellar nonfunctioning pituitary adenomas on sagittal and coronal magnetic resonance images using reference lines for the skull base level. In addition, the position of the optic chiasm in relation to the suprasellar adenoma was assessed. The findings were correlated with the degree of visual dysfunction and with the type of visual field defects (VFD). RESULTS: Seventy per cent of the patients suffered from VFD. The most frequent perimetric findings were bilateral (81·2%) or unilateral (10·1%) temporal hemifield defects. For the coronal view, a suprasellar extension of 12 mm was a practicable cut-off value for emergence of visual disturbances (87·0% sensitivity, 72·4% specificity). For the sagittal view, 8-mm suprasellar extension was a suitable cut-off for appearance of chiasma syndrome (87·0% sensitivity, 75·9% specificity). In five of seven cases without a chiasma syndrome despite a suprasellar extension >12 (coronal) and 8 mm (sagittal), the optic chiasm was found in an anterior position. No correlation was found between the position of the chiasm (i.e. anterior, superior or posterior) and the type of VFD (P = 0·647). A highly significant correlation was found between the decline of visual acuity and the suprasellar adenoma extension (P < 0·0001). CONCLUSION: Cut-off values possess a high sensitivity and specificity for imminent visual disturbances and are helpful for clinical decision-making. A delayed emergence of visual dysfunction may be observed with an anterior position of the optic chiasm.

Treatment Options in Cushing's Disease.

Endogenous Cushing's syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing's disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson's syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing's disease.

The development of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25). Part I: construction and psychometric properties.

OBJECTIVE: To develop a disease-specific questionnaire for Cushing's disease (CD), the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25). METHODS: Sources for item generation consisted of technical literature, interviews with patients and the rating of neurosurgeons, endocrinologists and a neuropsychologist. A preliminary inventory with 64 items was handed out to 63 CD patients. Twenty-eight patients filled out the questionnaire preoperative, the remaining 35 patients evaluated their health-related quality of life (HRQoL) retrospectively. Item reduction and scale generation followed the principles of classical test theory. Validation was performed with the WHOQoL-BREF. RESULTS: The final version of the Tuebingen CD-25 contained 25 items, showed high reliability (Cronbach's alpha = 0.93) and validity (r = -0.65) and includes the subdomains Depression, Sexual Activity, Environment, Eating Behaviour, Bodily Restrictions and Cognition. The retrospective rating of the Tuebingen CD-25 showed similar results compared to the pretreatment group. We found a non-linear correlation between the Tuebingen CD-25 scores and patients' age, younger (21-30 years) and middle-aged (51-60 years) patients having inferior HRQoL than patients between 31 and 50 years and older than 61 years. Preoperative 24 h urinary free cortisol (UFC) levels correlated significantly with the subscale Cognition and only marginally failed significance level for the subscale Eating Behaviour, while preoperative cortisol and ACTH levels did not correlate with any scale. CONCLUSION: The Tuebingen CD-25 is a valid and reliable instrument to evaluate HRQoL in CD. Based on impairment of HRQoL for the different subdimensions, specific support can be offered to the patients.

Developments in neuroendoscopy: trial of a miniature rigid endoscope with a multidirectional steerable tip camera in the anatomical lab.

The aim of this study is to assess field of view, usability and applicability of a rigid, multidirectional steerable video endoscope (EndActive) in various intracranial regions relevant to neurosurgical practice. In four cadaveric specimens, frontolateral, pterional, transnasal (to sella and clivus), interhemispheric (transcallosal and retrocallosal) and retrosigmoid approaches as well as precoronal burr holes for ventriculoscopy were performed. Anatomical target structures were defined in each region. We assessed field of view as well as optical and ergonomic features of the prototype. The EndActive is a 4-mm-diameter rigid video (endo)scope with an integral image sensor comprising an embedded light source. The viewing direction in a range of 160° can either be controlled by the computer keyboard or a four-way joystick mounted to the handle section of the endoscope. The endoscopic imaging system allows the operator to simultaneously see both a 160° wide-angle view of the site and an inset of a specific region of interest. The surgeon can hold the device like a microsurgical instrument in one hand and control movements precisely due to its reduced weight and ergonomic shape. The multiplanar variable-view rigid endoscope proved to be useful for following anatomical structures (cranial nerves I-XII). The device is effective in narrow working spaces where movements jeopardize the delicate surrounding structures. The multiplanar variable viewing mechanism in a compact device offers advantages in terms of safety and ergonomics. Improving the usability will probably optimize the applicability of endoscopic techniques in neurosurgery.

Contemporary microsurgical concept for the treatment of Cushing's disease: endocrine outcome in 83 consecutive patients.

BACKGROUND: Evidence suggests that occult adenoma remnants are responsible for persistent Cushing's disease (CD) following transsphenoidal surgery (TSS). To optimize the outcome, we have adapted our microsurgical concept. The influence of our surgical strategy on remission rate and pituitary function is presented. DESIGN AND PATIENTS: 83 patients undergoing TSS for newly diagnosed CD. An enlarged resection was performed in 36 patients. A modified exploration technique with radial incisions was performed in 19 patients in whom an adenoma was not readily detectable. RESULTS: The overall remission rate of primary surgery was 84·3% (70/83). A remission rate of 87·5% (63/72) was achieved in microadenomas. Six patients with microadenomas were re-operated for persistence, and hypercortisolism was corrected in five of them. With re-operation included, the overall remission rate for microadenomas was 94·4%. No procedure-related complications occurred in primary surgery. Of the patients in remission, 72·5% had early postoperative random cortisol levels below 2 µg/dl, 17·4% had cortisol levels between 2 and 5 µg/dl, and 10·1% had cortisol levels >5 µg/dl. 15·2% of the patients with microadenomas developed postoperative partial hypopituitarism and 3% diabetes insipidus. No increased rate of hypopituitarism was found with enlarged adenomectomy compared to selective adenomectomy. Only a slightly higher rate of partial hypopituitarism (23·1%) was found if extensive exploration was required. CONCLUSION: With our microsurgical concept, a high initial cure rate is achievable with minimal surgical morbidity. Enlarged adenomectomy has no adverse effect on the rate of postoperative hypopituitarism. Early repeat surgery is a successful option if CD persists.

The development of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25). Part II: normative data from 1784 healthy people.

OBJECTIVE: In part I of the study, a health-related quality of life (HRQoL) inventory for Cushing's disease (CD), the Tuebingen Cushing-25 quality of life inventory (Tuebingen CD-25) was developed. In this second part, we aimed to assess normative data from healthy controls (HC) with which the individual patients' scores can be compared. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-three patients with CD (52 women, 11 men) and 1784 HC (1210 women, 574 men) filled out the Tuebingen CD-25. MEASUREMENTS: HC received the inventory as a nondisease-specific quality of life questionnaire omitting the introductory sentence 'Because of my Cushing's disease' which was included in the CD group to be able to compare HRQoL in persons with and without CD. Slight and severe impairments were categorized according to the following principles: percent ranges >84.0% were classified as slight and percent ranges >95.0% as severe impairment. RESULTS: In 28.6% of our patients with CD, we found slight and in 41.3% severe impairment in the Total Score of the Tuebingen CD-25 compared with HC. Less than one-third of our patient sample presented with unimpaired HRQoL. In the patient population, impairment was found in all scales of the Tuebingen CD-25 to a similar extent (P = 0.444), pointing to the fact that all HRQoL domains are similarly impaired. We observed that female patients perceived a worse HRQoL than men in the domains depressive symptoms and social environment (P < 0.05). CONCLUSION: The Tuebingen CD-25 is a feasible instrument to assess HRQoL in CD in a clinical and investigative setting and provides normative data for all age groups and genders.

Parotid carcinoma metastasis to parietal meningioma: case report and molecular biologic considerations.

INTRODUCTION: A combination of factors as the meningioma's rich vascularity, its low metabolic rate, immunologic factors and the molecular pattern explains the affinity of some cancer metastasis to seed inside meningiomas. In this context, the importance of surface adhesion molecules is of rising interest. CASE REPORT: We report the exceptional case of a parotid carcinoma metastasis within a meningioma. A 68-year old male was referred to our hospital with headache and progressive right hemiparesis. Four years before he was diagnosed with parotid gland cancer for which he had undergone parotidectomy, radiation, neck dissection and chemotherapy. MRI showed a left sided high-parietal, dural-based, extraaxial, contrast enhancing tumor which was consequently removed microsurgically. Histological examination revealed a dedifferentiated parotid carcinoma metastasis inside a microcystic meningioma WHO grade I. Mechanisms that have been suggested to be responsible for metastasis into meningioma include meningiomas' rich vascularity, slow growth, their high collagen and lipid content, immunologic factors but also the expression of certain surface adhesion molecules, in particular E-cadherin. In the presented case E-cadherin immunostaining was strongly positive in the metastatic tissue that invaded the meningioma in a droppled-like fashion. We discuss the potential role of E-cadherin, re-expression of a modified E-cadherin complex and the potential importance of mesenchymal surface proteins in the pathophysiology of carcinoma metastasis into meningioma. CONCLUSION: Surface proteins of carcinoma cells might play a key role regarding their affinity to seed inside meningiomas. This might be a leading mechanism to the multifactorial process of carcinoma-to-meningioma metastasis.