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Michael Buchfelder

Publications and source records attributed to Michael Buchfelder.

At least 19 recordsLinked to original sources

Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas.

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.

Adolescent↗

Diffusion tensor imaging and optimized fiber tracking in glioma patients: Histopathologic evaluation of tumor-invaded white matter structures.

Fiber tracking is increasingly used to plan and guide neurosurgical procedures of intracranial tumors in the vicinity of functionally important areas of the brain. However, valid data concerning the reliability of tracking with respect to the actual pathoanatomical situation are lacking. We retrospectively correlated fiber tracking based on magnetic resonance (MR) DT imaging with the histopathological data of 25 patients with WHO grade II and III gliomas. Fiber tracking using the Fiber Assignment by Continuous Tracking (FACT) method was performed to investigate the integrity of white matter tracts in the surrounding border zone of the lesions. The tracking procedure was stopped when fractional anisotropy (FA) thresholds = 0.1, 0.15, 0.2, 0.25, and 0.3, or a tract turning angle >60 degrees were encountered. In 9 patients we were able to reconstruct brain fiber tracts at biopsy loci (2-32% tumor infiltration) using an FA threshold of 0.15 and 0.2, but not for a threshold of 0.25 or 0.3. The neurological outcome demonstrated potential tumor cell infiltration of functionally intact brain fiber tracts in the range of 2-8%. These findings may be useful in planning therapeutic approaches to gliomas in the vicinity of eloquent brain regions.

Adolescent↗

Combining fMRI and MEG increases the reliability of presurgical language localization: a clinical study on the difference between and congruence of both modalities.

To avoid neurological impairment during surgery near language-related eloquent brain areas, we performed presurgical functional brain mapping with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in 172 patients using language tasks. For MEG localizations, we used either a moving equivalent-current dipole fit or a current-density reconstruction using a minimum variance beamformer with a spatial filter algorithm. We localized the Wernicke and Broca language areas for every patient. We integrated the results into a frameless stereotaxy system. To visualize the results in the navigation microscope during surgery, we superimposed the fMRI and MEG findings on the brain surface. MEG and fMRI results differed in 4% of cases, and in 19%, one modality showed activation but not the other. In the vicinity of large gliomas, the BOLD (blood oxygenation level-dependent) effect was suppressed in 53% of our patients. Of the 124 patients who had surgery, only 7 patients (5.6%) experienced a transient language deterioration, which resolved in all cases. We used MEG and fMRI to show different aspects of brain activity and to establish validation between MEG and fMRI. We conclude that measurement by both MEG and fMRI increases the degree of reliability of language area localization and that the combination of fMRI and MEG is useful for presurgical localization of language-related eloquent cortex.

Brain↗

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.

BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. CONCLUSION: This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.

Adrenocorticotropic Hormone↗

Intradural, extramedullary spinal sarcoidosis: report of a rare case and review of the literature.

BACKGROUND: Spinal sarcoidosis represents a rare subgroup of neurosarcoidosis. Most spinal sarcoid lesions are intramedullary, and only eight cases of intradural, extramedullary sarcoid lesions have been reported hitherto. We describe the complete entity of intradural, extramedullary spinal sarcoidosis. METHODS: A 39-year-old woman presented with a 2-year history of slowly progressive numbness and paresthesia of the right medial upper arm followed by brachialgia and cephalgia. Magnetic resonance imaging revealed an intradural extramedullary T1 isointense and T2 hyperintense mass lesion near the right C3 nerve root exit C3, extending into the right neuroforamen. The cervical cord was not severely compressed. The mass lesion showed a high T2 signal. After intravenous administration of gadolinium-diethylenetriaminepentaacetic acid, there was marked enhancement of the process. RESULTS: The patient underwent a C2 to C3 laminoplasty and total resection of the intradural extramedullary tumor. The lesion encroached along the right neuroforamen, involving the C3 nerve root, and was grossly adherent to some of the rootlets. Histopathological examination of the specimen showed a noncaseating granulomatosis consistent with sarcoidosis. Postoperative testing did not reveal systemic involvement of sarcoidosis but bilateral hilar and mediastinal lymphadenopathy with normal lung parenchyma. The patient was therefore treated with corticosteroids. During the follow-up period of 16 months, the patient made a satisfactory recovery, though with persistent, distally pronounced sensory disturbance in the C3 or C4 root areas, and returned to work full-time. CONCLUSION: An extramedullary sarcoid lesion is rare. Unlike intramedullary sarcoid lesions, it can be totally removed. Even if systemic sarcoidosis is present, the patient can have an excellent recovery. From a review of the literature, we can hypothesize that intradural extramedullary spinal sarcoidosis may represent a very early stage of spinal sarcoidosis progressing to intramedullary intradural spinal sarcoidosis. The intradural extramedullary spinal sarcoidosis can be subdivided into a peripheral and a central subtype. Positive histological examination is required to establish the diagnosis since other diagnostic tests are unspecific.

Adult↗

Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach.

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.

Adolescent↗

Gliomas: histopathologic evaluation of changes in directionality and magnitude of water diffusion at diffusion-tensor MR imaging.

PURPOSE: To retrospectively correlate changes in fractional anisotropy (FA) and mean diffusivity in gliomas at diffusion-tensor magnetic resonance (MR) imaging with the degree of tumor cell infiltration determined histologically. MATERIALS AND METHODS: The institutional review board required neither ethics committee approval nor patient informed consent for this study. Twenty patients (eight women, 12 men; age range, 18-53 years) with glioma (seven World Health Organization grade II and 13 grade III tumors) underwent diffusion-tensor MR imaging at 1.5 T. Diffusion-tensor data were obtained with an echo-planar imaging sequence with six diffusion directions (b = 1000 sec/mm(2)), isotropic 1.9-mm voxels, and five averages. FA and mean diffusivity values were calculated from diffusion-tensor data. Coregistration with a three-dimensional MR imaging data set (used for stereotactic brain biopsies) enabled correlation of FA and mean diffusivity values with the histopathologic findings total cell number (CN), tumor CN, and percentage tumor infiltration (TI) by using linear, exponential, and logarithmic models. Student t and Mann-Whitney U tests were performed. RESULTS: Histopathologic findings of 77 MR image-guided stereotactic biopsies in all 20 patients were correlated with FA and mean diffusivity values at the biopsy locus. For FA and mean diffusivity, a logarithmic model showed strongest correlation with tumor CN and total CN; a linear model showed strongest correlation with percentage TI. For FA there were negative logarithmic (R = -0.802, P < .001) and linear (R = -0.796, P < .001) correlations with tumor CN and percentage TI, respectively. For mean diffusivity there were positive logarithmic (R = 0.557, P < .001) and linear correlations (R = 0.521, P < .001) with tumor CN and percentage TI, respectively. Differences between correlations for FA and mean diffusivity versus tumor CN (P < .001) and percentage TI (P < .001) were significant. CONCLUSION: FA is better than mean diffusivity for assessment and delineation of different degrees of pathologic changes (ie, TI) in glioma.

Adolescent↗

Intraoperative visualization for resection of gliomas: the role of functional neuronavigation and intraoperative 1.5 T MRI.

OBJECTIVE: To investigate how functional neuronavigation and intraoperative high-field magnetic resonance imaging (MRI) influence glioma resection. METHODS: One hundred and thirty-seven patients [World Health Organization (WHO) grade I: 20; II: 19; III: 41; IV: 57] underwent resection for supratentorial gliomas in an operative suite equipped with intraoperative high-field MRI and microscope-based neuronavigation. Besides standard anatomical image data including T1- and T2-weighted sequences, various functional data from magnetoencephalography (n=37), functional MRI (n=65), positron emission tomography (n=8), MR spectroscopy (n=28) and diffusion tensor imaging (n=55) were integrated in the navigational setup. RESULTS: Intraoperative MRI showed primary complete resection in 27% of all patients (I: 50%; II: 53%; III: 2%; IV: 28%). In 41% of all patients (I: 40%; II: 26%; III: 66%; IV: 28%) the resection was extended owing to intraoperative MRI increasing the percentage of complete resections to 40% (I: 70%; II: 58%; III: 17%; IV: 40%). Integrated application of functional navigation resulted in low post-operative morbidity with a transient new neurological deficit in 10.2% (paresis: 8.8% and speech disturbance: 1.4%) decreasing to a permanent deficit in 2.9% (four of 137 patients with a new or increased paresis). CONCLUSIONS: The combination of intraoperative MRI and functional navigation allows safe extended resections in glioma surgery. However, despite extended resections, still in the majority of the grade III and IV gliomas no gross total resection could be achieved owing to the extension of the tumor into eloquent brain areas. Intraoperative MRI data can be used to localize the tumor remnants reliably and compensate for the effects of brain shift.

Adolescent↗

History of the cushing reflex.

Increasing systolic and pulse pressure with bradycardia and respiratory irregularity are signs of increased intracranial pressure, leading to cerebral herniation and fatal brainstem compression. This phenomenon, the vasopressor response, is generally known as the Cushing reflex based on Harvey Cushing's experimental work in Europe in 1901 and 1902. However, similar experiments had been carried out decades earlier by others, notably Paul Cramer, Ernst von Bergmann, Ernst von Leyden, Georg Althann, Friedrich Jolly, Friedrich Pagenstecher, Henri Duret, Bernard Naunyn, and Julius Schreiber. Cushing initially failed to give credit to the work of these predecessors. Nonetheless, he studied the brain's reaction to compression more carefully than previous researchers and offered an improved explanation of the pathophysiology of the phenomenon named after him.

Animals↗

Primary hypophysitis: clinical-pathological correlations.

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.

Adult↗

Neuroprotection in primary brain tumors: sense or nonsense?

Primary brain tumors are generally difficult to treat because of the unique location of the lesions. In addition, normal brain structures are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is sometimes still injured, which can leave the patient in a debilitated state. The hemodynamic and metabolic state of such peritumoral brain tissue is not yet well understood, and there are only a small number of experimental hypotheses of its reaction and changes to the growing primary brain tumor. In addition, primary brain tumors may be influenced by certain anticancer drugs, which cause oxidative stress and consecutive cell death, or by gamma-irradiation. Currently, no established diagnostic methods exist to demonstrate and/or quantify the metabolic condition of the peritumoral tissue. The therapeutic strategy for possible pharmacological neuroprotection should, in the future, still be related to metabolic parameters, as well as in the peritumor tissue to treat primary brain tumors without risk to sensitive normal tissue. To achieve this aim, there has been particular emphasis on the biological behavior of primary brain tumors and peritumor tissue, as well as the potential correlation among them. Thus, priority should be given to identifying more target antigens in primary brain tumors and defining those cells present in the brain parenchyma that are essential to maintain a neuroprotective effect. However, at this time, the postinjury enhancement of neurogenesis appears to offer the best hope for long-lasting functional recovery following surgery of primary brain tumors.

Brain Neoplasms↗

Bone morphogenetic protein-4 inhibits corticotroph tumor cells: involvement in the retinoic acid inhibitory action.

The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.

Adenoma↗

Clinical review: Diagnosis and management of pituitary carcinomas.

Pituitary carcinomas are rare, making up some 0.2% of all pituitary tumors, but represent a particular challenge to clinical practice. The diagnosis of a pituitary carcinoma requires evidence of metastatic disease, either outside the central nervous system (CNS) or as separate noncontiguous foci within the CNS. They may present as typical pituitary adenomas, which reveal their malignant character only as time progresses, or as peculiarly aggressive tumors ab initio. Recent changes in histopathological classification have clarified many of the features of such tumors, including immunohistochemical staining for Ki-67 and p53, but to date none has been found to be pathognomonic. The majority of carcinomas are secretory, usually arising from corticotroph tumors or prolactinomas, but all histological types and secretory patterns are represented. Treatment is by surgery, transsphenoidal wherever possible, and conventional and stereotactic radiotherapy, but ultimately, a plethora of therapies may be required, including various attempts at medical therapy. Chemotherapy in some instances probably prolongs survival, but, in general, their progress from the diagnosis of carcinomatous changes is progressive and inexorable. However, we do not believe there will be any real prospect of long-term survival until the development and use of therapies targeted at specific molecular abnormalities.

Adrenocorticotropic Hormone↗

Meningiomas expressing and responding to cholecystokinin (CCK).

The effect of cholecystokinin (CCK) on cultured human meningioma derived cells was investigated. Exposure of meningioma cells for 6-12 days to CCK-8s (2-200 nM) resulted in a dose dependent stimulation of cell growth to a maximum of 1.1-fold over basal controls. A time course study showed stimulation of cell growth at day 3 followed by increase throughout day 6. The stimulatory effect of CCK on meningioma cell growth was completely abolished by a CCK-B specific receptor antagonist, L-365,260. Reverse-transcription of meningioma-derived RNA into cDNA followed by amplification by the polymerase chain reaction using specific primers for CCK peptide and its CCK-A and/B receptor revealed 100% presence of CCK peptide and CCK-B receptors mRNA whereas CCK-A receptor was expressed in 66% of the meningiomas. These results provide evidence that human meningioma cells possess CCK peptide and its receptors the activation of which leads to increase of cell growth possibly via an autocrine/paracrine mechanism.

Adult↗

Beta-catenin mutations in craniopharyngiomas and pituitary adenomas.

Craniopharyngiomas and pituitary adenomas are both tumors of the hypothalamic and pituitary region, respectively that are frequently associated with endocrine defects either because of direct involvement of hormone producing cells (most pituitary tumors) or because of secondary defects due to disturbance of hypothalamic function (some pituitary tumors and craniopharyngiomas). Some studies suggest that mutant beta-catenin gene cells in craniopharyngiomas and pituitary adenomas contribute to their tumorigenesis. DNA was extracted from 73 cranial tumors and subjected to polymerase chain reaction (PCR) with previously described primers encompassing glycogen synthase kinase-3beta phosphorylation sites of the beta-catenin gene. Sequenced PCR products for possible beta-catenin gene mutations showed a total of 7/43 alterations in adamantinomatous craniopharyngioma-derived DNA samples. Two previously described beta-catenin mutations in codon 33 TCT(Ser) > TGT(Cys) and codon 37 TCT(Ser) > TTT(Phe), whereas three novel mutations in codon 41 ACC(Thr) > ATC(Ile), codon 33 TCT(Ser) > TAT(Tyr) and codon 32 GAC(Asp) > AAC(Asn) were observed. None of the 22 pituitary adenomas and the eight papillary craniopharyngiomas analyzed presented any sequence alterations. These findings demonstrate an association between beta-catenin gene alterations and craniopharyngiomas of the adamantinomatous type. Since this gene product is involved with development, these results suggest that beta-catenin mutations may contribute to the initiation and subsequent growth of congenital craniopharyngiomas.

Adenoma↗

From trephination to tailored resection: neurosurgery in Germany before World War II.

Evidence exists that trephination was performed in Germany as early as the Stone Age. Late medieval barber surgeons further developed instruments and techniques for this procedure. Various surgeons performed individual cranial operations before the 1870s, and neurosurgery evolved as a distinct discipline in Germany around 1934. Before the 20th century, most cranial operations in Germany, as in other European countries, were performed for trauma. Since approximately 1870, a few individuals with a devoted interest in surgery of the nervous system have developed operative techniques for the brain and spinal cord. Wilhelm Wagner, Fedor Krause, Ernst von Bergmann, and Otfrid Foerster were among these pioneers. Through independent research based on careful clinical observation, these physicians contributed significantly to an understanding of the pathophysiology of nervous system disorders that could be treated surgically. They designed techniques, such as those used for intracranial pressure regulation, and developed operative procedures, such as the osteoplastic flap of Wagner, and cortical stimulation, which was performed by Krause and Foerster.

Barber Surgeons↗

Piezoelectric bone surgery: a revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note.

OBJECTIVE: Piezoelectric surgery represents an innovative, ultrasonic surgery technique for performing a safe and effective osteotomy or osteoplasty that contrasts with the traditional hard and soft tissue management methods with rotating instruments. METHODS: Because of its physical and mechanical properties, the definitive clinical advantage of piezoelectric bone surgery with regard to precision cutting lies in the sparing of vital neurovascular bundles or general soft tissue and better visualization of the surgical field, thus suggesting its great safety. Piezoelectric bone surgery has been previously described only in oral and maxillofacial operative procedures in adults. RESULTS: Five children between the age of 6 and 84 months were operated on for craniosynostosis, tethered cord, and an extraconal intraorbital tumor. The usefulness of piezoelectric bone surgery during neurosurgical procedures is presented for these cases. This technique is especially recommended when there are anatomic difficulties because of poor intraoperative visibility or the presence of delicate anatomic structures. CONCLUSION: The present preliminary report (comprising illustrative case reports) demonstrates and introduces for the first time the utility of piezoelectric bone surgery in cranial base and spinal surgery in children. Until now, there has been no documented neurosurgical experience of this technique even in adults.

Craniosynostoses↗