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Biomedical subjects

Michael Buchfelder

Publications and source records attributed to Michael Buchfelder.

36 records · Page 2Linked to original sources

Treatment of pituitary tumors: surgery.

Following a century of technical developments and refinements, a variety of standard operation techniques to date are available for the surgical treatment of pituitary tumors. The vast majority of the lesions can be dealt with satisfactorily utilizing transsphenoidal approaches. The goal of surgical treatment is rapid eradication of the tumor mass, decompression of visual pathways, and elimination of hormonal oversecretion while preserving the normal gland and avoiding potential surgical complications. The tumor's size, extension, and configuration and the magnitude of hormonal oversecretion, are the essential factors that decide whether all the goals can be reached. Another important factor is the individual skill and experience of the surgeon. Still, several lesions that are mainly developed outside of the sella require transcranial approaches, of which the pterional and subfrontal routes are the most widely used. With microsurgical techniques and standard approaches, mortality is far below 1% and morbidity is remarkably low. The most favorable surgical results are obtained with microadenomas, which in the MR image are depicted as distinct low intensity lesions. Only recently has the recovery of pituitary function following surgery been convincingly demonstrated. With the extended transsphenoidal approaches, lesions become accessible that previously have been considered contraindications for transsphenoidal surgery. The introduction of new technical gadgets such as neuronavigation, endoscopy, and intraoperative imaging open new avenues and, even more, widen the spectrum of accessible lesions. Indications for surgery, the preoperative workup, surgical techniques, results, limitations, and new technical developments are briefly reviewed in this article.

Adenoma↗

The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical 'cure'.

BACKGROUND AND AIM: The aim of this study was to illustrate the present role of transsphenoidal surgery as primary therapy in GH-secreting adenomas, and to compare the results concerning control of disease with previous series using older criteria of cure. METHOD: We report on a consecutive series of 688 acromegalic patients treated over a time period of 19 years. Biochemical cure was defined as normalisation of basal GH level, suppression of GH levels to below 1 ng/ml during an oral glucose load and normalisation of IGF-I levels. Of the 506 patients undergoing primary transsphenoidal surgery, a total of 57.3% postoperatively fulfilled the criteria used. RESULTS: The rate of biochemical 'cure' correlated with the magnitude of the initial GH levels, the tumour size and invasion. The overall complication rate was below 2%. Mortality in this series was 0.1% (1 of 688). During a follow-up period of 10.7 years only two recurrences (0.4%) occurred. However, in the patients treated by transcranial surgery and by repeat surgery the cure rate was found to be relatively low (5.2 and 21.3% respectively). CONCLUSIONS: These data suggest that surgery remains with very few exceptions the primary treatment of acromegaly for (i) a high cure rate, (ii) low morbidity, (iii) low recurrence rate and (iv) immediate decline of GH. Based on current criteria of cure, recurrences are uncommon. However, cure by surgery alone is improbable in patients harbouring extended, invasive tumours with high secretory activity, in whom further adjuvant treatment is mandatory.

Acromegaly↗

Reconstruction of skull bone defects using the hydroxyapatite cement with calvarial split transplants.

PURPOSE: We sought to present a new method for primary reconstruction of traumatic or tumor calvarial defects. PATIENTS AND METHODS: Forty-one patients underwent reconstruction of calvarial bone defects between October 1998 and December 2001. Among them were 19 patients who needed reconstruction of the calvaria due to traumatic bone loss. Five of these trauma cases had insufficient primary reconstruction of the calvaria. Tumor resection caused calvarial defects in 22 patients. For primary reconstruction of the skull bone defects, calvarial split grafts were used to cover the defect as accurately as possible. The monocortical layers of the calvaria were fixed with titanium miniplates. Irregular defects surrounding the transplanted regions were filled with hydroxyapatite cement. In one case of posttraumatic bone loss, hydroxyapatite cement alone was sufficient to reconstruct the defect. RESULTS: The follow-up of each patient was at least 6 months; the longest period was 38 months. Evaluated clinical and radiologic results are stable, showing no measurable side effects. CONCLUSION: Hydroxyapatite cement alone or in combination with calvarial split grafts gave clinically and aesthetically stable results in the reconstruction of skull bone defects. The cement can be used for many reconstruction possibilities in craniofacial surgery.

Adult↗

Olfactory neuroblastoma: the University of Erlangen-Nuremberg experience 1975-2000.

OBJECTIVE: Olfactory neuroblastoma constitutes a rare and, in clinical terms, biologically variable tumor of the nasal cavity, paranasal sinuses, and the base of the skull and presents a challenge to a modern multidisciplinary therapy. Generally acknowledged prognostic factors and a standard therapy fail to exist. METHODS: Between 1975 and 2000 we diagnosed and treated 26 patients with an olfactory neuroblastoma. According to Kadish's classification, 1 patient (4%) showed stage A, 16 patients (53%) stage B, and 11 cases (43%) stage C. Hyams grading was established in 81% of all cases. Fifty-two percent were thus classified as low-grade and 48% as high-grade tumors. Surgical therapy was performed on 23 patients (88.5%), surgery being the exclusive form of therapy (monotherapy) in 5 of these patients. Combined therapy was carried out in 18 cases (surgery, radiotherapy, chemotherapy). RESULTS: Currently, 16 of 26 treated patients (61.5%) are alive. The disease-specific 10- and 15-year survival determined according to Kaplan-Meier is 76.2%. Fifteen-year survival amounts to 86.7% for smaller tumors (Kadish A/B) and 63.6% for advanced tumors (Kadish C). Seven (26.9%) of the overall group of treated patients developed a recurrence. Salvage therapy was successful in 60% (3 of 5 patients). Fifteen-year survival following salvage therapy amounts to 60%. Patients with high-grade tumors exhibit a significantly reduced 10-year survival (40%) compared to patients with low-grade tumors (100%). CONCLUSIONS: The therapy of olfactory neuroblastoma calls for an interdisciplinary multimodal therapeutic strategy, particularly in the case of advanced tumors. Tumor staging and histopathologic grading according to Hyams are important factors for survival and prognosis. Aggressive salvage therapy can lead to a distinct improvement of long-term survival.

Adolescent↗

Ictal pleasant sensations: cerebral localization and lateralization.

Ictal pleasant feelings are a rare sign of focal epilepsies. The most popular description was performed by Dostojevskij, who reported an aura by Myshken in one of his books. No convincing evidence has been published concerning the cerebral localization of ictal happiness. In this study, the findings of 11 patients with ictal pleasant feelings are described. In eight patients, the origin of the focal epileptic activity was found in the temporal lobe (most often temporal inferior basal); in three patients, frontal or parietal lobe in addition to temporal lobe involvement was found. According to our findings ictal happiness is a localizing sign pointing to the ictal involvement of temporal mesiobasal areas. Lateralization to the right temporal lobe was found in seven and to the left temporal lobe in four patients.

Adolescent↗

Inverse correlation of epidermal growth factor receptor messenger RNA induction and suppression of anchorage-independent growth by OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in glioblastoma multiforme cell lines.

OBJECT: Quantitative and qualitative alterations in the epidermal growth factor receptor (EGFR) commonly occur in many cancers in humans, including malignant gliomas. The aim of the current study was to evaluate molecular and cellular effects of OSI-774, a novel EGFR tyrosine kinase inhibitor, on nine glioblastoma multiforme (GBM) cell lines. METHODS: The effects of OSI-774 on expression of EGFR messenger (m)RNA and protein, proliferation, anchorage-independent growth, and apoptosis were examined using semiquantitative reverse transcription-polymerase chain reaction, immunocytochemical analysis, Coulter counting, soft agar cloning, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling/fluorescence-activated cell sorting, respectively. All p53 genes were completely and bidirectionally sequenced. Suppression of anchorage-independent growth by OSI-774 was inversely correlated to the induction of EGFR mRNA during relative serum starvation (r = -0.74) and was unrelated to p53 status. Overall, suppression of anchorage-independent growth was a considerably stronger effect of OSI-774 than inhibition of proliferation. The extent of OSI-774-induced apoptosis positively correlated with both proliferation and anchorage-independent growth of GBM cell lines (r = 0.75 and 0.79, respectively). In a single cell line derived from a secondary GBM, exposure to concentrations of greater than or equal to 1 micromol/L resulted in a substantial net cell loss during proliferation studies. CONCLUSIONS: The induction of EGFR mRNA may constitute a cellular mechanism to counteract the inhibitory effect of OSI-774 on the anchorage-independent growth of GBM cells. In contrast, no considerable correlation could be established between baseline expression levels of EGFR (both mRNA and protein) in GBM cell lines and their biological response to OSI-774. The OSI-774 induced greater (p53-independent) apoptosis in more malignant GBM phenotypes and may be a promising therapeutic agent against secondary GBM.

Actins↗

Intraoperative low-field magnetic resonance imaging in pediatric neurosurgery.

BACKGROUND: Since the mid-1990s, the feasibility and indications of intraoperative magnetic resonance (MR) imaging have been investigated by different groups. The majority of examinations were carried out in adults. The aim of this study was to summarize our experience of over 5 years of intraoperative MR imaging in pediatric neurosurgery. METHODS: For scanning, we used a 0.2-Tesla Magnetom Open, which was placed in a radiofrequency-shielded twin operating theater, allowing surgery with standard instruments and additional neuronavigational guidance either in an adjacent operating room or directly in the radiofrequency cabin on the extended MR table, at the 5-G line. RESULTS: In total, 330 patients were investigated, among them 33 children who were younger than 17 years. We found four main indications for intraoperative MR imaging: the evaluation of cyst drainage (n = 9), of the extent of resection in epilepsy surgery (n = 6) and of the removal of pituitary tumors (n = 6) and gliomas and other brain tumors (n = 12). Intraoperative MR imaging allowed us to evaluate the extent of the resection or to monitor catheter placements and consecutive cyst alterations in all cases. In 2 tumor cases and 3 catheter placements, intraoperative imaging resulted in a modification of the surgical strategy. CONCLUSIONS: Intraoperative low-field MR imaging is a safe procedure; we did not encounter an increased morbidity in the children investigated. It serves as intraoperative quality control documenting the effects of surgery, e.g. the extent of a resection, which can then be compared to the treatment plan. Besides its most essential application in brain tumors, it also proved to be particularly helpful in children undergoing complicated catheter placements for cyst drainage, as well as in pituitary and epilepsy surgery.

Adolescent↗

Hormone markers in pituitary adenomas: changes within last decade resulting from improved method.

The significance of polyclonal antibodies for demonstration of hormone expression in pituitary adenomas was compared with the significance of monoclonal antibodies (MAbs). Adenomas were classified by light microscopic structures in paraffin- and epon-embedded sections, by immunostaining for all pituitary hormones, and in part by electron microscopy. In the first series, 166 adenomas were studied with polyclonal antibodies during 1990 and 1991. In the second series, 572 adenomas were immunostained with MAbs during 1999 and 2000. In the first series, a very typical type-specific hormone expression was demonstrable in 63.2% of adenomas in contrast to 91.1% in the second series. Consequently, in the first series 36.7% of adenomas expressed additional or atypical hormones in >10% of adenoma cells, whereas in the second series only 8.9% contained additional hormones. We conclude that MAbs show a clearer cutoff in immunostainings of pituitary hormones and therefore should be preferred for adenoma classification.

Adenoma↗

A polymorphism in the growth hormone-releasing hormone receptor gene: clinical significance?

Two forms of the growth hormone-releasing hormone (GHRH) receptor (GHRH-R) exist in terms of a polymorphism at codon 57. The most common allele possesses GCG, coding for Ala. This codon can also be ACG, replacing the Ala with Thr. The present study demonstrates that the latter occurs in about 20% of pituitary somatotrophinomas, removed from patients with acromegaly. Somatotrophinomas possessing the alternative allele respond, on average, more strongly to GHRH in terms of GH secretion in vitro than tumors which are homozygous for the more common allele. The distribution of the two allelic forms of the GHRH-R did not significantly differ between acromegalic and non-acromegalic subjects. Thus, while the alternative allelic forms may, at least partially, contribute to the variable response of serum GH levels to i.v. GHRH observed in acromegalic and normal subjects, it is unlikely that subjects possessing the rarer form containing Thr in place of Ala at residue 57 are at increased risk of developing acromegaly.

Acromegaly↗

Low-field magnetic resonance imaging for intraoperative use in neurosurgery: a 5-year experience.

The aim of this study was to evaluate the feasibility and point out the indications of intraoperative MR imaging in neurosurgical procedures. The MR imaging was performed using a 0.2-T scanner which was located in a radiofrequency-shielded operating theater. Three major setups for intraoperative imaging were possible: inside the scanner; at the 5-Gauss line; or in an adjacent operating theater. Additionally, in lesions adjacent to eloquent brain areas microscope- and pointer-based neuronavigation with integrated functional data was applied. Three hundred ten patients were investigated in the previous 5 years, among them gliomas ( n=95), pituitary tumors ( n=81), and 39 non-lesional cases in whom resective or disconnective epilepsy surgery was carried out. We did not observe any adverse effects due to intraoperative MR imaging. Image quality was sufficient to evaluate the extent of the tumor resection in the majority of cases. The main indications for intraoperative MR imaging were the evaluation of the extent of a resection in glioma, ventricular tumor, pituitary tumor, and in epilepsy surgery. Intraoperative MR imaging offers the possibility of further tumor removal during the same surgical procedure in case of tumor remnants, increasing the rate of complete tumor removal. Furthermore, the effects of brain shift, which would lead to inaccurate neuronavigation, can be compensated for by an update of the neuronavigation system with intraoperative MR image data.

Adult↗

Increased menin expression in sporadic pituitary adenomas.

BACKGROUND: Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour-suppressor gene are responsible for multiple endocrine neoplasia type 1, and menin, the MEN1 gene product, is usually downregulated or truncated in MEN1-associated adenomas. In contrast, exonic MEN1 mutations seem to be very rare in sporadic (MEN1-unrelated) pituitary adenomas, and it has been suggested that menin does not play a major role in these tumours. However, menin might be involved in sporadic adenoma tumorigenesis by downregulation through intronic mutations, epigenetic, posttranscriptional or posttranslational mechanisms. PATIENTS AND MEASUREMENTS: We screened MEN1 coding regions and flanking intronic sequences of 136 sporadic pituitary adenomas by temporal temperature gradient gel electrophoresis (TTGE) and studied menin expression by immunoblotting in 11 of these tumours. RESULTS: Sequencing of DNAs showing aberrant migration on TTGE revealed five somatic MEN1 mutations, including two missense mutations (F134L, E530K), a 2-bp deletion in exon 10 (c.1567-1568del) leading to a premature stop codon, and two 3-bp deletions in intron 5 (g.5236-5238del, g.5237-5239del). These mutations have not been reported previously in studies analysing the MEN1 gene. Immunoblotting showed menin upregulation in all adenomas examined (including one case with a missense mutation) from 1.7-fold to 10.4-fold (mean, 4.2-fold) compared to non-neoplastic adenohypophysis. CONCLUSIONS: Our data suggest that neither MEN1 mutations nor menin downregulation play a significant role in the development of sporadic pituitary adenomas.

Adenoma↗

Use of intraoperative magnetic resonance imaging in tailored temporal lobe surgeries for epilepsy.

PURPOSE: We investigated whether intraoperative magnetic resonance imaging (MRI) was able to assess immediately the extent of a tailored temporal lobe resection for epilepsy in comparison to delayed postoperative MRI. The recently proposed concept of an individually tailored procedure, preserving tissue not involved in seizures, leads to a variety of differently shaped resections. METHODS: For intraoperative imaging we used a Magnetom Open 0.2 Tesla scanner. Fifty-eight patients undergoing temporal lobe resections for pharmacoresistant epilepsy were investigated. Half of these were nonlesional. All patients had delayed postoperative follow-up scans, which were compared with the intraoperative, postresection images. RESULTS: In 49 (84%) of 58 cases, intraoperative MRI depicted the resection cavity identical to delayed postoperative studies. Complete resection of the visible lesion was primarily proved in 23 of the 29 cases. In two patients with lesions and in one nonlesional case, the resection was extended after intraoperative imaging, thus increasing the rate of total resections in gliomas from 73 to 87%. In four patients, an extension into eloquent areas did not allow complete removal. In the nonlesional cases (n = 29), the extent of tailored temporal resections also could be exactly documented intraoperatively. CONCLUSIONS: Intraoperative MRI allowed a reliable evaluation of the localization and extent of resection in epilepsy surgery within the operative procedure. Furthermore, it provided the possibility of an image-based correction of an initially incomplete resection, particularly in lesional cases. In the majority of patients, the intraoperative images would have been able to replace delayed postoperative MRI. However, in 16%, there were postoperative changes in the resection volume.

Adolescent↗

Effect of Dopamine Agonists on Lactotroph Adenomas of the Human Pituitary.

Dopamine (DA) agonists cause reduction of blood prolactin level and tumor shrinkage in most patients with lactotroph adenoma. Our aim was to investigate the cellular mechanism of tumor shrinkage by determining mitotic, MIB-1, p27, and apoptotic indices, as well as microvessel density (MVD), surface microvessel density (SMD). ploidy, and other nuclear parameters. Surgically removed lactotroph adenomas were selected from 29 patients, of whom 19 were treated with oral bromocriptine (BEC), long-acting injectable BEC (BEC-LAR), or quinagolide and 10 were untreated. In treated adenomas mitotic and MIB-1 indices were lower, whereas the apoptotic indices were not significantly higher compared to untreated adenomas. The decrease in MIB-1 labeling reached significance in adenomas exposed to quinagolide (p<0.05). Aside from the BEC-LAR treated group, wherein p27 expression was significantly reduced (p<0.05), p27 expression did not differ significantly between the treated and untreated groups. MVD density was significantly lower in the treated adenomas, whereas the decrease in SMD did not attain significance. The DNA ploidy and most other nuclear parameters did not differ significantly in the two groups. In conclusion, reduction of mitotic and MIB-1 indices indicates that suppression of cell proliferation contributes to tumor shrinkage, whereas p27 protein expression and apoptosis play no major role in the adenoma involution. Further studies are required to explain the effect of DA agonists on MVD and SMD.

Journal Article↗

Pituitary Corticotroph Adenoma in a Woman with Long-Standing Addison's Disease: A Histologic, immunocytochemical, Electron Microscopic, and In Situ Hybridization Study.

A 64-year-old woman with long-standing Addison's disease owing to destructive immune adrenalitis presented with hyperpigmentation and progressively increasing blood adrenocorticotrophic hormone (ACTH) levels. Magnetic resonance imaging demonstrated a pituitary microadenoma, which was removed by transsphenoidal surgery and investigated by histology, immunocytochemistry, transmission electron microscopy, and in situ hybridization (ISH). The morphologic studies revealed a basophilic, periodic acid-Schift (PAS)-positive pituitary adenoma immunoreactive for ACTH and B-endorphin and in several cells for a-subunit. By transmission electron microscopy, the tumor was a densely granulated corticotroph adenoma, which, by ISH, expressed pro-opiomelanocortin (POMC) mRNA. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis was an intriguing finding. Corticotroph adenomas in patients with long-standing Addison's disease were very rarely examined by morphology. Our report includes a detailed morphologic analysis and is the first demonstration of POMC mRNA in the tumor cells using ISH. The question of whether the adenoma was related to increased secretory activity secondary to protracted hypocorticism or developed independently unrelated to deranged endocrine homeostasis remains unresolved. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis favors the interpretation that hypothalamic stimulation played no major role in adenoma formation in our case.

Journal Article↗

EGFR but not PDGFR-beta expression correlates to the antiproliferative effect of growth factor withdrawal in glioblastoma multiforme cell lines.

BACKGROUND: The aim of the current study was to investigate a putative relationship between (i) growth characteristics (proliferation and tumorigenicity) of nine glioblastoma multiforme (GBM) cell lines under different growth-stimulating conditions in vitro and (ii) their basal expression of a panel of growth factor receptors/autocrine cytokines. MATERIALS AND METHODS: Basal expressions of the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-beta (PDGFR-beta), platelet-derived growth factor-AA (PDGF-AA) and PDGF-BB, tumor growth factor-alpha (TGF-alpha) and TGF-beta as well as tumor necrosis factor-alpha (TNF-alpha) were determined by immunocytochemistry at standard cell culture conditions (10% fetal calf serum [FCS]). Proliferation and tumorigenicity at 10% FCS and relative serum starvation (0.5% FCS) were assessed by using Coulter counting and soft agar cloning, respectively. RESULTS: The ratio between cell multiplications at 10% and 0.5% FCS over a 10-day period was defined as a measure of growth factor dependence of cellular proliferation. Expression of EGFR (but not of PDGFR-beta) strongly correlated to this ratio (Spearman rank correlation coefficient R = 0.87). No considerable correlations were present among other appropriate pairs of variables with biologically founded putative relationships. CONCLUSION: Greater expression of EGFR is associated with increased growth factor dependence of cellular proliferation. Our results strengthen the role of EGFR as a rational molecular target of therapeutic intervention in GBM.

Becaplermin↗