Biomedical subjects

R Fahlbusch

Publications and source records attributed to R Fahlbusch.

At least 37 records · Page 2Linked to original sources

PubMed2003

Glioma surgery evaluated by intraoperative low-field magnetic resonance imaging.

OBJECTIVE: To give an overview on intraoperative magnetic resonance (MR) imaging in glioma surgery. MATERIAL AND METHODS: MR imaging was performed using a 0.2T scanner, located in a radiofrequency-shielded operating theatre. Two setups were used: surgery either in a neighbouring operating theatre, or directly at the 5G line. Additionally, in gliomas adjacent to eloquent brain areas microscope- or pointer-based neuronavigation with integrated functional data was applied. 106 gliomas were among the 330 patients investigated in the last 5 years. RESULTS: We did not observe complications attributable to intraoperative MR imaging. Image quality was sufficient to evaluate the extent of the tumour resection in the majority of cases. Intraoperative imaging revealed remaining tumour in 63%. In a total of 26% patients further tumour could be removed due to the results of intraoperative imaging, increasing the rate of complete tumour removal especially in the low-grade tumours. The additional use of functional neuronavigation prevented an increased morbidity. CONCLUSION: Intraoperative MR imaging offers the possibility of further tumour removal during the same surgical procedure in case of tumour remnants, increasing the rate of complete tumour removal. The effects of brain shift can be compensated for using intraoperative image data for updating.

Adolescent↗

PubMed2003

Preliminary experience in glioma surgery with intraoperative high-field MRI.

OBJECTIVE: To apply a new setup, combining the benefits of high-field magnetic resonance imaging (MRI) with microscope-based neuronavigation, providing anatomical and functional guidance, in glioma surgery. MATERIAL AND METHODS: MR imaging was performed using a 1.5 T scanner, located in a radiofrequency-shielded operating theatre. The patient is lying on a rotating operating table, which is locked at the 160 degree position for surgery at the 5 G zone and turned into the scanner for imaging. The microscope, placed in the 5 G zone, in combination with a ceiling mounted navigation system enables microscope-based neuronavigation; integrated data from magnetoencephalography and functional MRI provide functional guidance. RESULTS: 126 patients were investigated with intraoperative high-field MRI, among them were 37 patients with gliomas. In the biopsy/catheter group (n = 8) MRI reliably depicted the needle position or the location of catheter placement. In the group with glioma resection (n = 29) intraoperative MRI revealed that the surgical objective was not achieved in 28%, leading to further tumour removal. We did not observe complications attributable to intraoperative high-field MRI. Image quality was not diminished by the operating room equipment, so that there was nearly no noticeable difference between pre- and intraoperative image quality. Neuronavigational guidance was applied in 31 patients: the integrated use of functional data prevented an increased morbidity despite extended resections. CONCLUSION: Intraoperative high-field MRI allows a reliable delineation of the extent of resection in glioma surgery. If the surgical objective was not met, a modification of the surgical strategy during the same operation is possible, thus leading to more radical resections. Furthermore, high-field MRI offers increased image quality and a much broader spectrum of different imaging modalities, compared to previous intraoperative low-field systems.

Adolescent↗

PubMed2003

Image-guided removal of supratentorial cavernomas in critical brain areas: application of neuronavigation and intraoperative magnetic resonance imaging.

In a retrospective study the postoperative results of 26 patients operated on for supratentorial cavernous hemangiomas either deep-seated or near eloquent brain areas are summarized. An exact surgical approach to these lesions is essential to prevent neurological deterioration. Three different navigation systems were used and compared according to their clinical applicability. Complete removal of the lesion was obtained in all patients of this series. In six cases (23 %) functional data from magnetoencephalography or functional magnetic resonance imaging were integrated into the navigational setup. In 14 cases (54 %) intraoperative magnetic resonance imaging was performed. The follow-up time was 3 - 26 months (mean: 10 months). In the postoperative course one patient (3.8 %) developed a hemiparesis, another one developed quadrantopia. Nineteen patients presented with preoperative seizure history, 16 of these (84 %) had no further or rare seizures after surgery. The better results in seizure control were achieved in those patients with shorter duration of seizure history before surgery. The study indicates that the application of neuronavigation allows surgery on supratentorial cavernous hemangiomas in critical brain areas with low morbidity. The intraoperative visualization of eloquent cortex areas by integration of functional data allows a fast identification and exemption of eloquent brain areas, preventing neurological deterioration. Furthermore, the intraoperative MR resection control ensures a complete resection and illustrates the minimal invasive approach.

Adolescent↗

PubMed2003

Endocrine findings in patients with optico-hypothalamic gliomas.

OBJECTIVES: Optico-hypothalamic gliomas (OHG) are an important differential diagnosis in suprasellar tumors. Visual impairment and hydrocephalus are the most frequent findings at presentation. However, only limited data are available about endocrine disturbances in these lesions. PATIENTS AND METHODS: 38 consecutive patients (19 children) were studied retrospectively. Clinical assessment and endocrinological evaluation of pituitary and hypothalamic functions (combined pituitary stimulation test, ITT, CRH-GRH test) were performed before and after (1 week and 3 months) the neurosurgical procedure. RESULTS: Only three patients showed clinical features of endocrine deficiency initially. 16 children and 15 adults out of the 38 patients (31/38, 81.6 %) showed no abnormality in their hormone values when assessed with the combined pituitary stimulation test alone or using more sophisticated investigations such as ITT and CRH-GRH test (72.2 %). Patients with hypothalamic disturbances (8 out of 38, 21 %) had endocrine abnormalities more frequently than those without (57.1 % vs. 9 %, p < 0.05), as assessed by ITT and CRH-GRH-test. CONCLUSIONS: In contrast to other suprasellar tumors, endocrine deficiencies are surprisingly rare in optico-hypothalamic gliomas despite their large size, especially in the absence of hypothalamic disorders. This may be used as a criterion in the differential diagnosis of these lesions, in addition to the radiological findings.

Adolescent↗

PubMed2003

Frameless stereotactic brain biopsy procedures using the Stealth Station: indications, accuracy and results.

This study presents the results of 57 stereotactic brain biopsies using a frameless neuronavigation system, the Stealth Station. The supratentorial lesions had a mean diameter of 33 mm and a mean distance of 32 mm from the entry point at brain surface. In all cases the stereotactic procedure was planned in the preoperative 3-D magnetic resonance data set. In seven cases additional data for identification of eloquent brain areas was integrated from magnetoencephalography or functional magnetic resonance imaging. During surgery the samples were sent to neuropathological examination and the operation completed after the confirmation of pathological tissue. Using this method, in 56 cases a pathological tissue was obtained and a diagnostic yield of 98% was achieved. In two cases (3.5%) a new neurological deficit remained (hemiparesis and visual field deficit). The mean operation time was 92 minutes including examination of frozen sections. The results of our series demonstrate, that frameless stereotactic systems can also be reliably applied for biopsy of supratentorial lesions larger than 15 mm. Frameless stereotaxy in combination with intraoperative pathological confirmation is a safe and reliable method for stereotactic brain biopsy with a diagnostic yield comparable to frame-based stereotaxy.

Adolescent↗

PubMed2002

[Use of magnetoencephalography and functional neuronavigation in planning and surgery of brain tumors].

The role of magnetoencephalography (MEG) in neurology has been established for basic research, epilepsy, and functional brain mapping. The presurgical localization of functionally important brain areas has evolved as an important application of MEG. Both neurologists and neurosurgeons can use this method for decision-making and planning of nonsurgical or surgical treatment in brain tumors. The integration of functional brain mapping data into neuronavigation systems may help to minimize postoperative morbidity. This is especially important in low-grade gliomas, in which a potential benefit of surgery is only achieved when the tumor has been resected completely, whereas neurological deterioration means a substantial loss of quality of life during the survival time. This report addresses the utility of MEG combined with neuronavigation in the treatment of brain tumors adjacent to eloquent brain areas.

Adolescent↗

PubMed2002

Localisation of the sensorimotor cortex during surgery for brain tumours: feasibility and waveform patterns of somatosensory evoked potentials.

OBJECTIVE: Intraoperative localisation of the sensorimotor cortex using the phase reversal of somatosensory evoked potentials (SEPs) is an essential tool for surgery in and around the perirolandic gyri, but unsuccessful and perplexing results have been reported. This study examines the effect of tumour masses on the waveform characteristics and feasibility of SEP compared with functional neuronavigation and electrical motor cortex mapping. METHODS: In 230 patients with tumours of the sensorimotor region the SEP phase reversal of N20-P20 was recorded from the exposed cortex using a subdural grid or strip electrode. In one subgroup of 80 patients functional neuronavigation was performed with motor and sensory magnetic source imaging and in one subgroup of 40 patients the motor cortex hand area was localised by electrical stimulation mapping. RESULTS: The intraoperative SEP method was successful in 92% of all patients, it could be shown that the success rate rather depended on the location of the lesion than on preoperative neurological deficits. In 13% of the patients with postcentral tumours no N20-P20 phase reversal was recorded but characteristic polyphasic and high amplitude waves at 25 ms and later made the identification of the postcentral gyrus possible nevertheless. Electrical mapping of the motor cortex took up to 30 minutes until a clear result was obtained. It was successful in 37 patients, but failed in three patients with precentral and central lesions. Functional neuronavigation indicating the tumour margins and the motor and sensory evoked fields was possible in all patients. CONCLUSION: The SEP phase reversal of N20-P20 is a simple and reliable technique, but the success rate is much lower in large central and postcentral tumours. With the use of polyphasic late waveforms the sensorimotor cortex may be localised. By contrast with motor electrical mapping it is less time consuming. Functional neuronavigation is a desirable tool for both preoperative surgical planning and intraoperative use during surgery on perirolandic tumours, but compensation for brain shift, accuracy, and cost effectiveness are still a matter for discussion.

Adolescent↗

PubMed2002

Neuronavigation: concept, techniques and applications.

Neuronavigation provides intraoperative orientation to the surgeon, helps in planning a precise surgical approach to the targetted lesion and defines the surrounding neurovascular structures. Incorporation of the functional data provided by functional MRI and magnetoencephalography (MEG) with neuronavigation helps to avoid the eloquent areas of the brain during surgery. An intraoperative MRI enables radical resection of the lesions, the possibility of immediate control for tumor remnants and updates of neuronavigation with intraoperative images to compensate for brain shift. In this study, the experience of 432 patients undergoing neuronavigation assisted neurosurgical interventions using either the pointer-based or microscope-based navigational systems at the University of Erlangen-Nuremberg, Germany is presented. The procedures included stereotactic biopsy (n=53), stereotactic cyst puncture/ventricular drainage (n=15), eloquent cortex/tumor localization to facilitate tumor resection, assessment of neurovascular structures in the vicinity of tumors of the sellar-suprasellar regions, skull base, posterior fossa and ventricular region (n=252), and, surgery for epilepsy (n=9). Functional brain mapping using fMRI and MEG and their integration with neuronavigation was carried out in 24 and 128 patients respectively. The simultaneous use of intraoperative MRI to look for the remaining tumor was done in 159 patients and the update of navigational data was carried out in 17 patients. The mean system accuracy obtained by using both the fiducial registration as well as anatomical landmark-surface fitting computer algorithm was 1.81 mm. This study reviews the relative merits and demerits of the pointer and microscope based navigational systems and also highlights the role of functional brain mapping and intraoperative MRI, when integrated with neuronavigation, in the surgical decision-making to offer the chances of more radical resections with minimal morbidity.

Adolescent↗

PubMed2001

Long-term results after microvascular decompression in essential hypertension.

BACKGROUND AND PURPOSE: In 1998, 8 patients with severe, intractable arterial hypertension and MR tomography-demonstrated neurovascular contact of a looping artery at the root entry zone of cranial nerves IX and X, causing neurovascular compression, underwent neurosurgical decompression. The short-term results showed a normalization of blood pressure with a markedly reduced antihypertensive drug regimen in 7 patients. To determine the longer-term outcome concerning blood pressure and secondary organ damage after neurovascular decompression, we studied these 8 operated patients prospectively for a mean follow-up of 3.5 years after surgical intervention. METHODS: Eight hypertensive patients who had undergone microsurgical decompression were monitored every 6 months after surgery to assess blood pressure (by 24-hour ambulatory pressure readings) and the need for antihypertensive medication. To evaluate secondary organ damage, echocardiographic assessment of left ventricular hypertrophy, fundoscopic assessment of hypertensive lesions, and analysis of renal function and proteinuria were done. RESULTS: Three of the 8 operated patients remained normotensive in the long-term period with decreased antihypertensive medication. Two patients required gradual increases of antihypertensive medication after the first postoperative year, after which arterial blood pressure levels were 10% to 15% lower than preoperative levels. Three patients suffered serious cardiovascular and renal complications, with the incidence of lethal intracerebral hemorrhage in 1 patient and end-stage renal disease in 2 patients, of whom 1 experienced sudden cardiac death. CONCLUSIONS: The long-term results verify that microsurgical decompression is a successful alternative therapy in a certain subgroup of patients with arterial hypertension due to neurovascular compression. However, the relevance of the looping artery in the other cases, who did not improve, is not clear. Prospective studies to elucidate the pathophysiological role of neurovascular abnormalities and arterial hypertension are needed.

Adult↗

PubMed2001

New approach to localize speech relevant brain areas and hemispheric dominance using spatially filtered magnetoencephalography.

We used a current localization by spatial filtering-technique to determine primary language areas with magnetoencephalography (MEG) using a silent reading and a silent naming task. In all cases we could localize the sensory speech area (Wernicke) in the posterior part of the left superior temporal gyrus (Brodmann area 22) and the motor speech area (Broca) in the left inferior frontal gyrus (Brodmann area 44). Left hemispheric speech dominance was determined in all cases by a laterality index comparing the current source strength of the activated left side speech areas to their right side homologous. In 12 cases we found early Wernicke and later Broca activation corresponding to the Wernicke-Geschwind model. In three cases, however, we also found early Broca activation indicating that speech-related brain areas need not necessarily be activated sequentially but can also be activated simultaneously. Magnetoencephalography can be a potent tool for functional mapping of speech-related brain areas in individuals, investigating the time-course of brain activation, and identifying the speech dominant hemisphere. This may have implications for presurgical planning in epilepsy and brain tumor patients.

Adult↗

PubMed2001

CDKN2A/p16 inactivation is related to pituitary adenoma type and size.

p16 (CDKN2A, MTS1, INK4A) status at genomic and protein levels was analysed and correlated with clinico-pathological features in 72 pituitary adenomas. Methylation of CpG islands of promoter/exon 1 sequences was found in most gonadotroph, lactotroph, plurihormonal, and null cell adenomas (36 of 44, 82%), but it was rare in somatotroph (1 of 13 cases, 8%) and corticotroph adenomas (1 of 15 cases, 7%). Homozygous CDKN2A deletion was restricted to rare somatotroph (15%) and corticotroph adenomas (13%). Immunohistochemical p16 protein expression was observed in the normal adenohypophysis, whereas it was absent in 60 of 72 (83%) tumours and reduced in another ten (14%) tumours. Staining for p16 was only seen in 5 of 15 (33%) corticotroph, 3 of 13 (23%) somatotroph, 3 of 5 (60%) plurihormonal, and 1 of 19 (5%) null cell adenomas. p16 immunonegativity without CDKN2A methylation or deletion occurred in 22 tumours, including most somatotroph and corticotroph adenomas (15 of 28, 54%). Both CDKN2A alterations and p16 negativity were related to larger tumour size. Patients with p16-negative tumours were older than patients with p16-positive tumours. These data suggest that p16 down-regulation is common in all adenoma types. The mechanisms of p16 down-regulation probably involve CDKN2A methylation in most types, but remain to be determined in somatotroph and corticotroph adenomas. These findings also suggest that p16 down-regulation is usually not an initial event, but is acquired during adenoma progression.

Adenoma↗

PubMed2001

Correlation of sensorimotor activation with functional magnetic resonance imaging and magnetoencephalography in presurgical functional imaging: a spatial analysis.

In this study we investigated the spatial heterotopy of MEG and fMRI localizations after sensory and motor stimulation tasks. Both methods are frequently used to study the topology of the primary and secondary motor cortex, as well as a tool for presurgical brain mapping. fMRI was performed with a 1.5T MR system, using echo-planar imaging with a motor and a sensory task. Somatosensory and motor evoked fields were recorded with a biomagnetometer. fMRI activation was determined with a cross-correlation analysis. MEG source localization was performed with a single equivalent current dipole model and a current density localization approach. Distances between MEG and fMRI activation sites were measured within the same anatomical 3-D-MR image set. The central region could be identified by MEG and fMRI in 33 of 34 cases. However, MEG and fMRI localization results showed significantly different activation sites for the motor and sensory task with a distance of 10 and 15 mm, respectively. This reflects the different neurophysiological mechanisms: direct neuronal current flow (MEG) and secondary changes in cerebral blood flow and oxygenation level of activated versus non activated brain structures (fMRI). The result of our study has clinical implications when MEG and fMRI localizations are used for pre- and intraoperative brain mapping. Although both modalities are useful for the estimation of the motor cortex, a single modality may err in the exact topographical labeling of the motor cortex. In some unclear cases a combination of both methods should be used in order to avoid neurological deficits.

Adolescent↗

PubMed2001

Intraoperative compensation for brain shift.

BACKGROUND: Tumor removal, brain swelling, the use of brain retractors, and cerebrospinal-fluid drainage all result in an intraoperative brain deformation that is known as brain shift. Thus, neuronavigation systems relying on preoperative image data have a decreasing accuracy during the surgical procedure. Intraoperative image data represent the correct anatomic situation, so their use may compensate for the effects of brain shift. METHODS: In a series of 16 brain tumor patients, we used intraoperative magnetic resonance (MR) imaging to obtain 3-D data, which were then transferred to the microscope-based neuronavigation system. With the help of bone fiducial markers these images were registered intraoperatively, updating the neuronavigation system. RESULTS: In all patients the updating of the neuronavigation system with the intraoperative MR data was successful. It led to reliable neuronavigation with high accuracy; the mean registration error of the update procedure in all patients was 1.1 mm. The updating procedure added about 15 minutes to the operation time. In all patients the area suggestive of remaining tumor was reached and the additional tumor could be resected, resulting in a complete tumor removal in 14 patients. In the remaining patients extension of the tumor into eloquent brain areas prevented a complete excision. CONCLUSIONS: The update of a neuronavigation system with intraoperative MR images reliably compensates for the effects of brain shift. This method allows completion of tumor removal in some difficult brain tumors.

Adolescent↗

PubMed2001

Current management of prolactinomas.

Prolactinomas constitute the largest group of pituitary adenomas in autopsy series. However, their relative incidence in recent surgical series is much less impressive since medical treatment with dopamine agonists is routinely employed, which in many cases leads to tumor shrinkage and normalization of prolactin levels. The clinical symptoms of hyperprolactinemia are menstrual dysfunction and galactorrhea in women and loss of libido and potency in men. Prolactinomas may present also as space occupying sellar mass lesions impinging on the adjacent structures like the pituitary gland, cavernous sinus and optic nerves. The standard primary treatment is medical by dopamine agonists. Prolactinomas are the prototype of tumors, the growth of which can be reliably and safely inhibited by specific drugs other than cytostatic chemotherapy. These unfortunately have side effects, like orthostatic hypotension, nausea and vomiting. The effects induced by dopamine agonists are suppressive but not tumoricidal. Thus, the therapeutic effect is only maintained as long as the drug is administered. Consequently. in most cases, treatment has to be continued life-long with a few exceptions, in whom normoprolactinemia persists even after discontinuation of dopamine agonists. Main indications of surgery in prolactinomas are intolerance of the medication, and tumors not responding to dopamine agonists. Occasionally, these may ultimately require radiation therapy. Remission rates in large series of surgically treated prolactinomas vary between 54% and 86%. In our consecutive series of 540 surgically treated prolactinomas, the normalization rate after transsphenoidal surgery basically depended on the preoperative prolactin levels, tumor size and extension. The remission rate of 82% in microprolactinomas with initial prolactin levels <200 ng/ml would even in small adenomas make one consider surgical treatment as an interesting alternative to long-term medical treatment.

Animals↗

PubMed2001

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone-secreting and non-functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans.

The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.

Adenoma↗

PubMed2001

Elevated inferior petrosal sinus levels of PTHrP in a patient with Cushing's disease.

PTHrP has been found in various tissues, including prolactinomas and growth hormone producing adenomas. The function and clinical importance of PTHrP are poorly understood. We report the case of a 25-year-old female patient with hirsutism. Autonomous ACTH-dependent hypercortisolism was documented by endocrine testing. Magnetic resonance imaging (MRI) revealed a 3-mm intrasellar hypointense lesion in the left side of the pituitary gland. The inferior petrosal sinus sampling disclosed a gradient of ACTH left central/peripheral of 30.5 and right central/peripheral of 2.0 and suggested the diagnosis of a left-sided pituitary ACTH secreting microadenoma. Interestingly, we found elevated PTHrP levels in the left inferior petrosal sinus with a gradient of 4.7 compared to peripheral venous blood and of 3.6 compared to the right sinus. Our results fit very well to the concept of a para-/autocrine secretion of PTHrP which has been proposed recently and suggest a role in the regulation of cell growth of pituitary adenomas.

Adenoma↗

PubMed2001

Intraoperative magnetic resonance imaging combined with neuronavigation: a new concept.

OBJECTIVE: Intraoperative image data may be used not only to evaluate the extent of a tumor resection but also to update neuronavigation, compensating for brain shift. To date, however, intraoperative magnetic resonance imaging (MRI) can be combined only with navigation microscopes that are separated from the magnetic field, thus requiring time-consuming intraoperative patient transport. To help solve this problem, we investigated whether a new navigation microscope can be used within the fringe field of the MRI scanner. METHODS: The navigation microscope was placed at the 5-G line of a 0.2 MRI device. Patients were positioned lying down directly on the table of the scanner, with their heads placed approximately 1.5 m from the center of the magnet, fixed in an MRI-compatible ceramic head holder. Standard operating instruments were used. For intraoperative imaging, we slid the table into the center of the magnet in less than 30 seconds. RESULTS: By use of this setup, we operated on 22 patients. In all patients, anatomic neuronavigation could be used in combination with intraoperative MRI. In addition, in 12 patients, functional data from magnetoencephalographic or functional MRI studies were integrated, resulting in functional neuronavigation. We did not encounter adverse effects of the low magnetic field during navigation. Moreover, intraoperative imaging was not disturbed by the navigation microscope and vice versa. CONCLUSION: Functional neuronavigation and intraoperative MRI can be used essentially simultaneously without the need for lengthy intraoperative patient transport. The combination of intraoperative imaging with functional neuronavigation offers the opportunity for more radical resections and fewer complications.

Adolescent↗

PubMed2001

Dopamine D2 receptor gene expression in human adenohypophysial adenomas.

The inhibitory effects of dopamine on adenohypophysial cells are mediated via dopamine subtype 2 receptor (D2R). Dopamine agonists inhibit hormone release and induce tumor shrinkage in most prolactin-secreting adenomas, whereas in other adenoma types such effects are sporadic. We investigated D2R gene expression by in situ hybridization (ISH) and immunocytochemistry in different types of pituitary adenomas. By ISH, a variable D2R signal was detected in 79 of 89 cases: 4 of 6 densely granulated and 8 of 8 sparsely granulated somatotroph, 4 of 4 mammosomatotroph, 7 of 7 mixed somatotroph-lactotroph, 4 of 4 acidophil stem cell, 16 of 16 sparsely granulated lactotroph, 11 of 16 corticotroph (functioning and silent), 3 of 4 silent subtype 3, 5 of 5 thyrotroph, 5 of 6 gonadotroph, 5 of 6 null cell, and 7 of 7 oncocytic adenomas. By immunocytochemistry, D2R protein was localized in cytoplasm and nuclei of 60 of 62 adenomas. In lactotroph adenomas, long-acting bromocriptine (BEC-LAR) induced a major increase in D2R mRNA, which was not accompanied by increased D2R immunoreactivity, suggesting mRNA stabilization. In conclusion, D2R gene is expressed in the majority of pituitary adenomas representing all tumor types. The significance of nuclear localization of D2R protein remains to be clarified.

Adenoma↗