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1.
J Neurol Surg A Cent Eur Neurosurg ; 84(4): 305-315, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36400110

ABSTRACT

BACKGROUND: Although the world is experiencing a deficit in the neurosurgical workforce, the number of neurosurgeons in Germany has increased within the last two decades. The aim of the present study was to assess the neurosurgical workforce in Germany, compare it to European countries, and assess structures in neurosurgical departments in Germany. METHODS: Data regarding the number of neurosurgeons in Germany as well as the number of departments, beds, cases, and neurosurgical procedures were gathered. A survey among German neurosurgical departments was performed to assess the structure of neurosurgical care. Furthermore, another survey among European countries was performed to acquire information regarding the number of surgeons and the regulation of training. RESULTS: From 2000 to 2019, the number of board-certified neurosurgeons in Germany increased by 151% from 973 to 2,446. During the same period, the German population increased by only 1% from 82.26 million to 83.17 million. Thus, the number of neurosurgeons per 100,000 inhabitants increased from 1.18 to 2.94. The increase of neurosurgeons is not paralleled by an increase in departments or an increase in neurosurgical procedures within the active neurosurgical departments. In comparison to the participating European countries, where the number of neurosurgeons per 100,000 inhabitants ranged from 0.45 to 2.94, with Germany shows the highest number. CONCLUSIONS: German institutions of medical administration urgently need to consider regulation of neurosurgical specialist training to prevent a further uncontrolled increase in neurosurgeons in a manner that is not adapted to the needs of neurosurgical care for the German population. Actions might include a regulation of entry to the training and of the number of training sites. Furthermore, an integration of non-physician assistant health care professionals and delegation of non-surgical workload from neurosurgeons is necessary. A further increase in neurosurgeons would be associated with a decrease in the surgical caseload per surgeons during training and after board certification, which might compromise the quality of neurosurgical care.


Subject(s)
Neurosurgery , Humans , Germany , Neurosurgeons , Neurosurgical Procedures , Workforce
2.
Acta Neurochir (Wien) ; 155(2): 373-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23263479

ABSTRACT

BACKGROUND: Subdural (SDE) and epidural empyema (EDE) are life-threatening intracranial infections. They require immediate diagnosis and treatment. However, in some cases, magnet resonance imaging (MRI) is not able to contribute to diagnosis; therefore, surgical exploration is indicated. Hollow screws used for decompression of chronic subdural haematoma (cSDH) are valuable tools for minimally invasive biopsy in awake patients when SDE and EDE are suspected. METHODS: Between 2006 and 2010, eight patients in our department underwent biopsy of a suspected SDE or EDE using hollow screws. In these cases, MRI or computed tomography (CT) were not able to provide sufficient diagnostic security to indicate primary craniotomy. Diagnostic and therapeutic efficacy was evaluated on preoperative and postoperative imaging. The focus was on qualitative parameters, such as contrast enhancement or impaired diffusion on diffusion-weighted images (DWI). RESULTS: The application of the hollow screw under local anaesthesia permitted an exact diagnosis in all cases. In one case, the suspected diagnosis of cSDH could be refuted by diagnostic puncture. In four cases of uncertain diagnosis, the application of the hollow screw revealed a cSDH. Seven of eight patients previously received neurosurgical treatment; three of those cases were SDE or EDE and four were cSDH. Cases of SDE and EDE needed further craniotomy after diagnostic puncture, whereas patients with cSDH were sufficiently treated by hollow screws. CONCLUSIONS: Given their comparably wide diameter, hollow screws allow a sufficient sample size and, therefore, lead to precise diagnosis of SDE and EDE without significant operative risks or strains for the patient.


Subject(s)
Biopsy/instrumentation , Decompression, Surgical/instrumentation , Empyema, Subdural/diagnosis , Hematoma, Subdural, Chronic/surgery , Aged , Cohort Studies , Craniotomy , Empyema, Subdural/etiology , Empyema, Subdural/therapy , Female , Hematoma, Subdural, Chronic/complications , Hematoma, Subdural, Chronic/diagnosis , Humans , Male , Middle Aged , Patient Selection , Predictive Value of Tests
3.
Acta Neurochir (Wien) ; 154(9): 1663-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22847726

ABSTRACT

BACKGROUND: Frame-based stereotaxy remains the "gold standard" for cerebral biopsies and functional neurosurgery though new frameless stereotactic systems are evolving continually. As the technique of frameless stereotaxy gains increasing acceptance among neurosurgeons, this study assesses the feasibility of a system for frameless image-guided stereotaxy. METHODS: All patients biopsied for intracranial lesions between February 2007 and August 2010 using the BrainLAB VarioGuide frameless stereotactic system were evaluated prospectively. Prior to surgery, patients underwent magnetic resonance (MR) imaging; additionally, fluoroethyl-tyrosine (FET)-positron emission tomography (PET) images were acquired and fused to MR images in selected cases. Biopsy trajectory length, lesion volume, procedure duration, and diagnostic yield were assessed. RESULTS: Ninety-six diagnostic biopsies in 91 patients were evaluated. Lesion volume ranged from 0.17 to 121.8 cm(3); trajectory length from 25.3 to 101.9 mm. Diagnostic yield was 93.8%. Mean operation time from skin incision to wound closure was 42 min; in the operating room, it was 99 min. CONCLUSIONS: Clinical experience indicates VarioGuide to be safe and accurate. Reachable range of lesion localisation appears to be comparable to a frame-based stereotaxy system. Operation times are brief. The unique design of this frameless stereotactic system allows real-time visual feedback of needle positioning.


Subject(s)
Brain Neoplasms/pathology , Brain/pathology , Glioma/pathology , Image-Guided Biopsy/instrumentation , Magnetic Resonance Imaging/instrumentation , Neuronavigation/instrumentation , Positron-Emission Tomography/instrumentation , Adult , Aged , Equipment Design , Feasibility Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Tumor Burden/physiology , Young Adult
4.
Acta Neurochir (Wien) ; 154(2): 349-57, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22009015

ABSTRACT

BACKGROUND: Intradural metastases of nonneurogenic origin represent an extremely rare manifestation of systemic cancer. The respective literature is very scarce. METHODS: We retrospectively evaluated nine patients with intradural metastases treated surgically from March 2006 until today at our department. RESULTS: Four metastases were intramedullary and five intradural extramedullary. Localisation along the spine involved: cervical n = 3, thoracic n = 3, and conus/cauda n = 3. Five patients were female and four male, with a median age of 71 years. Histology showed: breast cancer n = 2, NSCLC (non-small cell lung cancer) n = 2, SCLC (small cell lung cancer) n = 1, colon carcinoma n = 1, malignant skin melanoma n = 1, squamous cell carcinoma of the skin n = 1, and ovarian carcinoma n = 1. Holospinal dissemination in terms of leptomeningeal carcinomatosis according to MRI or positive CSF (cerebrospinal fluid) cytology, respectively, was found in four patients. Gross total resection was achieved in four patients and debulking in five. Results of surgical decompression were: six patients (67%) exhibited immediate improvement of neurological symptoms and/or pain; four of them even improved according to the McCormick Scale score (44%); two patients (22%) were unchanged, and one (11%) exhibited worsening of neurological symptoms after surgery. Median survival time after surgery was 7.3 months. CONCLUSIONS: Intradural metastases are associated with limited survival time. Accordingly, the aim of surgery is strictly palliative. The majority of patients benefit with respect to neurological deficit/pain (67%) independent of the extent of resection. Thus, decompressive surgery is recommended to increase the quality of life.


Subject(s)
Carcinoma/secondary , Carcinoma/surgery , Spinal Cord Neoplasms/secondary , Spinal Cord Neoplasms/surgery , Aged , Aged, 80 and over , Carcinoma/pathology , Cauda Equina , Cervical Vertebrae , Fatal Outcome , Female , Humans , Laminectomy , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Peripheral Nervous System Neoplasms/diagnosis , Peripheral Nervous System Neoplasms/pathology , Peripheral Nervous System Neoplasms/secondary , Peripheral Nervous System Neoplasms/surgery , Retrospective Studies , Spinal Cord Neoplasms/pathology , Survival Rate , Thoracic Vertebrae
5.
Eur J Endocrinol ; 162(5): 879-86, 2010 May.
Article in English | MEDLINE | ID: mdl-20145047

ABSTRACT

CONTEXT: Information about the risk and course of coronary artery disease (CAD) in acromegaly is limited. OBJECTIVE: To evaluate CAD risk in acromegalic patients at diagnosis and after successful treatment during follow-up. SUBJECTS AND METHODS: Twenty-five consecutive patients (age 45.1+/-10.6 years, 15 women) were studied at the time of diagnosis, and 19 patients were re-evaluated after 4.6+/-1.1 years. The European Society of Cardiology (ESC) risk score was calculated, and a cardiac computed tomography was performed for detection and quantification (Agatston score (AS)) of coronary artery calcium (CACs). Fifty age-, sex-, and CAD risk-matched subjects and CAC data from the population-based Heinz Nixdorf Recall (HNR) study served as controls. RESULTS: In 21 of the 25 patients, the 10-year risk of developing CAD according to the ESC risk score was low (<10%) and high (>20%) in four patients. The AS was lower than in controls (2.6+/-7.9 vs 66+/-182; P=0.014) and less patients had a positive CAC (AS>0) (20 vs 48%, P=0.024), which in the acromegalic patients was less than expected from the HNR study. The AS did not correlate with GH excess or disease duration. In 19 acromegalic patients, who were in remission and re-evaluated after 4.6+/-1.1 years, the ESC risk (P=0.102) and the AS (P=0.173) did not change significantly and no symptomatic CAD event occurred. CONCLUSION: CAD risk in newly diagnosed acromegalic patients was low and remained stable after successful treatment. CAC was lower than in controls suggesting that GH excess per se does not carry an additional CAD risk.


Subject(s)
Acromegaly/complications , Coronary Artery Disease/etiology , Adult , Calcium/metabolism , Coronary Artery Disease/diagnostic imaging , Coronary Vessels/metabolism , Echocardiography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Risk , Tomography, X-Ray Computed
6.
Cancer Sci ; 100(10): 1856-62, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19681905

ABSTRACT

Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment.


Subject(s)
Brain Edema/pathology , Brain Neoplasms/pathology , Glioma/pathology , Animals , Aquaporin 4/biosynthesis , Brain Edema/etiology , Brain Neoplasms/complications , Glial Fibrillary Acidic Protein/biosynthesis , Glioma/complications , Immunohistochemistry , Inflammation/etiology , Inflammation/pathology , Intramolecular Oxidoreductases/biosynthesis , Macrophage Migration-Inhibitory Factors/biosynthesis , Magnetic Resonance Imaging , Microglia/metabolism , Microscopy, Fluorescence , Neoplasm Transplantation , Neoplasms, Experimental/complications , Neoplasms, Experimental/pathology , Rats
7.
Neurosurgery ; 65(1): 54-62; discussion 62, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19574825

ABSTRACT

OBJECTIVE: The aim of this study was to assess the outcome of cranial nerve and endocrine function after transsphenoidal decompression for symptomatic cavernous sinus (CS) meningioma. METHODS: Between 1991 and 2007, 21 patients (19 women and 2 men; mean age, 51.1 +/- 10.6 years) harboring symptomatic CS meningiomas underwent transsphenoidal decompression. Sufficient bone removal, opening of the inferomedial wall of the CS, and tumor debulking were performed. RESULTS: Notably, the grading of preoperative optomotoric paresis improved in 15 of the 17 patients who presented with that symptom. Complete recovery could be achieved in 8 patients. Complete recovery rates in patients with preoperative grading of "good," "fair," and "poor" were 77.7%, 20%, and 0%, respectively (P = 0.0088). Improvement of cranial nerve dysfunction was found in 32 of 34 deficits. No worsening of cranial nerve function occurred. Endocrinologically, the prolactin level was normalized in 13 of the 17 patients with preoperative hyperprolactinemia. Recovery of growth hormone deficiency and hypogonadism were found in 3 patients (37.5%) and 1 patient (33.3%), respectively. Seventeen patients were followed for more than 3 years. Of these 17 patients, 12 patients received initial postoperative adjuvant radiotherapy. The overall tumor control rate after surgery with initial adjuvant radiotherapy was 100% (median follow-up, 65 months; range, 36-126 months). CONCLUSION: Transsphenoidal decompression is a safe and effective treatment to improve cranial nerve and endocrine dysfunction in patients with symptomatic CS meningiomas. The less severe optomotoric nerve palsy before surgery, the better the chance of complete recovery of its function. Combined with adjuvant radiotherapy, this minimally invasive management also provided excellent long-term tumor control.


Subject(s)
Cavernous Sinus/surgery , Decompression, Surgical/methods , Meningeal Neoplasms/surgery , Meningioma/surgery , Adult , Aged , Cavernous Sinus/pathology , Chi-Square Distribution , Cranial Nerve Diseases/etiology , Cranial Nerve Diseases/surgery , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging/methods , Male , Meningeal Neoplasms/pathology , Meningeal Neoplasms/radiotherapy , Meningioma/pathology , Meningioma/radiotherapy , Middle Aged , Postoperative Complications , Prolactin/metabolism , Radiotherapy/methods , Retrospective Studies
8.
Brain Pathol ; 19(3): 357-64, 2009 Jul.
Article in English | MEDLINE | ID: mdl-18540944

ABSTRACT

Activating beta-catenin (CTNNB1) mutations can be identified in the majority of adamantinomatous craniopharyngiomas (adaCP), suggesting an aberrant Wnt signaling pathway in this histopathologically peculiar tumor entity. However, there is no proven evidence that nuclear translocation of beta-catenin is associated with CTNNB1 mutations and target gene activation. We performed a laser-microdissection-based study comparing beta-catenin accumulating vs. non-accumulating tumor cells. Mutational analysis and gene expression profiling using real-time polymerase chain reaction were conducted in adamantinomatous and papillary tumor specimens. Target gene activation, that is, over-expression of Axin2 could be detected in adaCP, especially in tumor cells with nuclear beta-catenin accumulation. In addition, increased expression of BMP4 was identified in the accumulating cell population, which supports the hypothesis of an oral ectodermal origin. Interestingly, accumulating and non-accumulating tumor cell populations carried CTNNB1 mutations within exon 3. We extended the analysis, therefore, towards genetic regions encoding for membrane linkage and active/passive nuclear transport mechanisms (exon 4 and exon 8-13), but could not detect any alteration. This is the first report demonstrating an association between nuclear beta-catenin accumulation and target gene activation in adaCP. The results confirm the Wnt signaling pathway as molecular basis of the distinct and challenging clinical and morphological phenotype of adaCP.


Subject(s)
Craniopharyngioma/genetics , Signal Transduction/physiology , Transcriptional Activation , Wnt Proteins/metabolism , beta Catenin/metabolism , Adolescent , Adult , Axin Protein , Bone Morphogenetic Protein 4/genetics , Cell Nucleus/metabolism , Cell Nucleus/pathology , Child , Child, Preschool , Craniopharyngioma/metabolism , Craniopharyngioma/pathology , Cytoskeletal Proteins/genetics , DNA Mutational Analysis , Female , Gene Expression , Humans , Immunohistochemistry , Male , Microdissection , Pituitary Neoplasms/genetics , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Reverse Transcriptase Polymerase Chain Reaction , Wnt Proteins/genetics
9.
Acta Neuropathol ; 113(5): 585-90, 2007 May.
Article in English | MEDLINE | ID: mdl-17221204

ABSTRACT

Activation of the Wnt/wingless signalling cascade is a key mechanism in developmental morphogenesis, whereas aberrant nuclear accumulation of beta-catenin in adult tissues seems to be associated with neoplastic transformation and tumour progression. Adamantinomatous craniopharyngiomas carry activating mutations in exon 3 of the beta-catenin gene, which results in a distinct pattern of nuclear beta-catenin accumulation in up to 95% of respective tumour specimens. To better characterise the impact of nuclear beta-catenin aggregation in these neoplasms, we systematically examined epithelial differentiation and cell cycle-associated molecules in accumulating compared to non-accumulating tumour cell clusters using a cohort of 65 adamantinomatous craniopharyngiomas. Monoclonal antibodies directed against cytokeratins 5/6 (CK5/6) were utilised to differentiate squamous from simple epithelium, the latter being identified by immunoreactivity for cytokeratins 8 and 18 (CK8/CK18). Intriguingly, nuclear beta-catenin accumulation in whorl-like tumour cell clusters was always associated with a distinct CK8 and CK18 immunoreactivity, whereas surrounding non-accumulating tumour cells showed exclusively squamous differentiation indicated by CK5/6 expression. In addition, a low proliferation activity combined with an increased expression of p21(WAF1/CIP1), a key control protein of the cell cycle, was observed in beta-catenin accumulating cells. Our data support an impact of nuclear beta-catenin on different cytoarchitectural and epithelial differentiation patterns in adamantinomatous craniopharyngiomas.


Subject(s)
Craniopharyngioma/metabolism , Craniopharyngioma/pathology , Epithelium/growth & development , Morphogenesis/physiology , beta Catenin/metabolism , Adolescent , Adult , Aged , Cell Differentiation , Cell Nucleus/metabolism , Cell Nucleus/pathology , Child , Child, Preschool , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Epithelium/pathology , Female , Gene Expression Regulation, Neoplastic/physiology , Humans , Keratin-18/metabolism , Keratin-8/metabolism , Male , Middle Aged
10.
Am J Surg Pathol ; 30(12): 1595-603, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17122517

ABSTRACT

Clinical and histopathologic differentiation of cystic lesions from the sellar region, that is, craniopharyngiomas (CPs) and Rathke cleft cysts (RCCs), is challenging and has paramount importance with respect to variable clinical manifestation and adapted surgical treatment strategies in both entities. Here, we retrospectively evaluated clinico-pathologic findings in 81 patients presenting with a cystic tumor located in the sellar region. All patients underwent transsphenoidal or transcranial resections. Microscopic inspection of surgical specimens identified CP in 51 patients, and RCC in 30 patients. Amongst the panel of immunohistochemical marker proteins used for histopathologic analysis, nuclear accumulation of beta-catenin was detectable only in CP. On the basis of the histopathologic and immunohistochemical analysis, clinical presentation (sex, age, ophthalmologic, and endocrinologic deficits), imaging (tumor location, size, and calcification), as well as a description of cyst contents obtained during operation were retrospectively evaluated. In purely cystic CPs, an isointense signal was more frequent in T1-weighted magnetic resonance images and calcification of the tumor capsule in computed tomography scans. In addition, the size of RCC was smaller and this tumor entity was more often located within the sella. Aberrant (nuclear) immunohistochemical staining for beta-catenin appeared, however, as most reliable factor for the differentiation between purely cystic CPs and RCCs, whereas tumor location, tumor size, and calcification of the tumor capsule were less consistent parameters. The data are compatible with distinct pathogenic pathways associated with these related histopathologic entities.


Subject(s)
Cell Nucleus/metabolism , Central Nervous System Cysts/pathology , Craniopharyngioma/pathology , Pituitary Neoplasms/pathology , beta Catenin/metabolism , Adolescent , Adult , Aged , Biomarkers, Tumor/metabolism , Cell Nucleus/pathology , Central Nervous System Cysts/metabolism , Central Nervous System Cysts/surgery , Child , Child, Preschool , Craniopharyngioma/metabolism , Craniopharyngioma/surgery , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Male , Middle Aged , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/surgery , Treatment Outcome
11.
Eur J Endocrinol ; 155(1): 101-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16793955

ABSTRACT

OBJECTIVE: Primary hypophysitis comprises of three distinct histomorphological entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the three subtypes for diagnostic and treatment strategies have yet not been well characterized. METHODS: Endocrine function, visual fields and acuity as well as magnetic resonance imaging characteristics were assessed before and after transphenoidal surgery in the largest series of 31 patients with primary hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases). RESULTS: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was associated with other autoimmune diseases (24%). Visual fields and acuity abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and granulomatous hypophysitis most often resulted in severe dysfunction of the adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients presenting with xanthomatous hypophysitis most often, mild anterior pituitary axis failure was documented and posterior pituitary involvement was hardly found. The outcome after transphenoidal biopsy was generally favorable. Pre- or postsurgical glucocorticoid treatment was very effective in 75% of the lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid therapy was less effective in granulomatous or xanthomatous hypophysitis. CONCLUSION: Diffuse destruction of the complete pituitary gland including the infundibulum has to be considered in lymphocytic and granulomatous hypophysitis, whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to compression of the pituitary gland without alteration of the pituitary stalk and optic chiasm can be assumed.


Subject(s)
Pituitary Diseases/complications , Pituitary Diseases/pathology , Pituitary Gland/pathology , Adult , Female , Glucocorticoids/therapeutic use , Granuloma/pathology , Hormone Replacement Therapy , Hormones/blood , Humans , Hypophysectomy , Lymphocytes/pathology , Magnetic Resonance Imaging , Male , Meningitis/etiology , Middle Aged , Pituitary Function Tests , Pituitary Gland/physiopathology , Pregnancy , Visual Acuity/physiology , Visual Fields/physiology , Xanthomatosis/pathology
12.
Neurosurgery ; 58(6): 1108-18; discussion 1108-18, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16723890

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the role of transsphenoidal selective adenomectomy alone or in combination with adjuvant therapy in treatment of recurrent Cushing's disease. METHODS: A total of 16 patients with recurrent Cushing's disease underwent reoperation, 15 via a transsphenoidal approach and one via a combined transsphenoidal/transcranial approach. Selective adenomectomies were performed in 13 patients and hemihypophysectomies were performed in three patients. Endocrinologically, recurrence was diagnosed by an overnight 2-mg dexamethasone suppression test. All patients underwent a 1.5-T magnetic resonance imaging scan, and eight patients underwent inferior petrosal sinus sampling. RESULTS: After selective adenomectomy, six of the 13 patients went into remission. Recurrence always occurred at the localization of the original tumor. In three patients without intraoperative tumor detection, hypophysectomy did not lead to remission. In 10 patients with persistent disease, adjuvant therapy (radiotherapy, adrenalectomy) led to normalization of basal cortisol levels in eight patients and clinical remission in one patient. One patient was lost to follow-up. In 10 patients, no evidence of an adenoma was visible on the preoperative magnetic resonance imaging scan. Inferior petrosal sinus sampling allowed correct prediction of the tumor localization in two of eight patients. CONCLUSION: By performing repeated selective adenomectomy, patients with recurrent Cushing's disease can be cured without the risk of endocrine deficits or major complications. Dynamic endocrine tests are of paramount importance for surgical decision making. Imaging and inferior petrosal sinus sampling are not helpful in locating the recurrent tumor. If normalization can not be achieved, adjuvant therapy is mandatory.


Subject(s)
Pituitary ACTH Hypersecretion/surgery , Adenoma/diagnosis , Adenoma/surgery , Dexamethasone , Female , Glucocorticoids , Humans , Hydrocortisone/blood , Hypophysectomy , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local , Pituitary ACTH Hypersecretion/blood , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/surgery , Radiotherapy, Adjuvant , Recurrence , Remission Induction , Reoperation
13.
Acta Neuropathol ; 111(3): 264-71, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16421738

ABSTRACT

Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade are required for cytokines, growth factors, G-proteins and hormones (growth hormone and prolactin). Gatekeepers in this pathway are the suppressor of cytokine signalling (SOCS) family of proteins. Their expression level is epigenetically regulated by DNA methylation. We have investigated the CpG island methylation status of SOCS-1 in a cohort of pituitary adenomas (PA; n=57), craniopharyngiomas (CP; n=30) and normal pituitary tissue (NP; n=11) using methylation sensitive single-strand conformation polymorphism analysis (MS-SSCP) and direct sequencing. SOCS-1 hypermethylation was identified in 51% (29/57) of surgical specimens obtained from PA patients. 83% of these tumours were clinically silent. In contrast, no methylation of SOCS-1 was observed in CPs or NPs. Quantitative real-time PCR and western blot analysis confirmed reduced SOCS-1 expression in the majority of pituitary adenomas. The data is compatible with epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK-STAT pathway in PA. This appears to contribute particularly to those tumours characterized by a hormone-inactive status.


Subject(s)
Adenoma/metabolism , Gene Silencing , Pituitary Neoplasms/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Adenoma/genetics , Adolescent , Adult , Aged , Craniopharyngioma/genetics , Craniopharyngioma/metabolism , DNA Methylation , DNA, Neoplasm/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Janus Kinases/physiology , Male , Middle Aged , Pituitary Neoplasms/genetics , STAT Transcription Factors/physiology , Signal Transduction/physiology , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins/genetics
14.
Eur J Endocrinol ; 153(2): 239-48, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16061830

ABSTRACT

OBJECTIVE: The aim of the study was to evaluate the effect of intraoperative high-field (1.5 Tesla) magnetic resonance imaging (MRI) on the results of transsphenoidal surgery of GH-secreting pituitary macroadenomas. METHODS: Twenty-three acromegalic patients (mean tumor size, 25 +/- 12 mm; untreated preoperative GH, 4.2-159 microg/l; IGF-I, 349-1111 microg/l) were investigated by intraoperative high-field MRI. If intraoperative imaging depicted an accessible tumor remnant, resection was continued. RESULTS: In five patients intraoperative MRI led to further tumor removal, two of these met the consensus criteria for endocrine remission after 3 months. In two patients basal GH and oral glucose tolerance test (OGTT) were <2 microg/l, only IGF-I was slightly elevated, and in one patient GH was <5 microg/l and OGTT was 2 microg/l, with elevated IGF-I. Final intraoperative MRI showed no tumor remnants in 14 patients; eight of them met the consensus criteria for remission of acromegaly. In the patients with MRI showing incomplete removal (four suspect findings and five patients with intended partial removal) none was normalized. CONCLUSION: With regard to the patients with a tumor configuration in whom complete tumor removal was considered (n = 18), intraoperative MRI increased the rate of endocrine normalization from 33 to 44% applying the consensus criteria, and improved endocrine outcome to 'nearly normalization' in another 17%. With regard to preoperative GH levels and tumor size, intraoperative MRI can help to achieve endocrine remission in patients who are normally considered not to be curable. However, taking GH as the tumor marker, even intraoperative high-field MRI was not able to detect tumor remnants in every case.


Subject(s)
Acromegaly/pathology , Acromegaly/surgery , Intraoperative Care/methods , Magnetic Resonance Imaging/methods , Adenoma/pathology , Adenoma/surgery , Adult , Aged , Female , Humans , Intraoperative Care/instrumentation , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Sphenoid Bone/surgery , Treatment Outcome
15.
Acta Neuropathol ; 109(6): 589-97, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15891929

ABSTRACT

Dysregulation of the Wnt signalling pathway contributes to developmental abnormalities and carcinogenesis of solid tumours. Here, we examined beta-catenin and adenomatous polyposis coli (APC) by mutational analysis in pituitary adenomas (n=60) and a large series of craniopharyngiomas (n=41). Furthermore, the expression pattern of beta-catenin was immunohistochemically analysed in a cohort of tumours and cysts of the sellar region including pituitary adenomas (n=58), craniopharyngiomas (n=57), arachnoidal cysts (n=8), Rathke's cleft cysts (n=10) and xanthogranulomas (n=6). Whereas APC mutations were not detectable in any tumour entity, beta-catenin mutations were present in 77% of craniopharyngiomas, exclusively of the adamantinomatous subtype. All mutations affected exon 3, which encodes the degradation targeting box of beta-catenin compatible with an accumulation of nuclear beta-catenin protein. In addition, a novel 81-bp deletion of this exonic region was detected in one case. Immunohistochemical analysis confirmed a shift from membrane-bound to nuclear accumulation of beta-catenin in 94% of the adamantinomatous tumours. Aberrant distribution patterns of beta-catenin were never observed in the other tumour entities under study. We conclude that beta-catenin mutations and/or nuclear accumulation serve as diagnostic hallmarks of the adamantinomatous variant, setting it apart from the papillary variant of craniopharyngioma.


Subject(s)
Craniopharyngioma/genetics , Cytoskeletal Proteins/genetics , Genes, APC , Pituitary Neoplasms/genetics , Sella Turcica/pathology , Trans-Activators/genetics , Adolescent , Adult , Aged , Base Sequence , Child , Child, Preschool , Craniopharyngioma/metabolism , DNA Mutational Analysis , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Pituitary Neoplasms/metabolism , Polymorphism, Single-Stranded Conformational , Reverse Transcriptase Polymerase Chain Reaction , beta Catenin
16.
Curr Opin Neurol ; 17(6): 693-703, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15542978

ABSTRACT

PURPOSE OF REVIEW: Treatment of pituitary adenomas remains an interdisciplinary challenge involving neurosurgeons, endocrinologists and radiation oncologists. The different disciplines inaugurated advanced techniques to improve the already relatively high standard of outcome for the benefit of patients, covering molecular pathogenesis, novel therapeutic strategies for the different adenoma subtypes, developments in perioperative magnetic resonance imaging and radiosurgical management of pituitary adenomas. RECENT FINDINGS: Despite the progress achieved in medical treatment of hormone-secreting pituitary adenomas throughout recent years, surgery remains the primary therapy of choice except for prolactinomas. Recent studies in molecular pathogenesis aiming to find novel therapy targets and reports on new pharmacological drugs effecting GH-secreting pituitary adenomas are reviewed (for example, lanreotide 60, SOM320 and pegvisomant). Advances in surgical treatment of pituitary macroadenomas are obtained by pre- and especially by intraoperative (high-field) MRI offering a higher rate of safe and complete tumor removal. Therapy pitfalls mentioned in the literature throughout the last year as well as key points in the management of pituitary adenomas with focus on acromegaly and Cushing's disease are reported. Adjuvant irradiation for recurrent or residual adenomas is often a necessity. In comparison to standard conventional radiation strategies an increasing number of radiation oncologists and neurosurgeons report their experience with radiosurgery especially for smaller tumor remnants in pituitary adenomas. SUMMARY: Recent molecular studies suggest a new level of complexity in the tumorigenisis of pituitary adenomas in terms of possible cell-type-specific molecular changes. Except for prolactinomas surgery remains the primary treatment for pituitary adenomas. New pharmacological drugs achieve very encouraging endocrine results although no long-term follow-up is available so far. The results of trans-sphenoidal surgery will further improve by modern imaging techniques, especially by applying intraoperative high-field magnetic resonance imaging and neuronavigation. The results of radiosurgical techniques with regard to tumor control are mostly convincing, but definitive conclusions on long-term recurrence and/or late complications are not reliable so far.


Subject(s)
Adenoma/diagnosis , Adenoma/therapy , Antineoplastic Agents/pharmacology , Neurosurgical Procedures/methods , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Humans , Magnetic Resonance Imaging/trends , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/trends , Neurosurgical Procedures/trends , Postoperative Complications/prevention & control , Radiosurgery/trends
17.
Acta Orthop Scand ; 74(3): 270-6, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12899546

ABSTRACT

In a cadaver study, we prepared 20 matched pairs of human femora using chipped-tooth broaches and robotic milling with the same geometry. For robotic bone preparation the CASPAR robotic system with a rotating milling head was used. Cancellous bone was irrigated with 1 liter of pulsed lavage and the specimens were embedded in specially-designed pots. After vacuum mixing, bone cement was introduced in a retrograde manner and subjected to a standard pressure protocol with a constant force of 3,000 N. Radiographs were taken and horizontal sections were obtained at predefined levels, using a diamond saw. Microradiographs of the bone slices were taken, digitized and analyzed to assess cement penetration into cancellous bone. No femoral fractures or fissures occurred with either preparation technique. The microradiographic evaluation showed no morphometric differences between chipped-tooth broaches and robotic milling as regards cement penetration into cancellous bone. Therefore, in the presence of pulsed lavage, we conclude that robotic bone preparation does not increase cement penetration into cancellous bone of the proximal end of the femur.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Bone Cements/therapeutic use , Cementation/methods , Femur/surgery , Osteotomy/methods , Polymethyl Methacrylate/therapeutic use , Robotics/methods , Therapy, Computer-Assisted/methods , Analysis of Variance , Cadaver , Humans , Microradiography , Osteotomy/instrumentation , Pressure , Robotics/instrumentation , Therapeutic Irrigation/methods , Therapy, Computer-Assisted/instrumentation
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