Biomedical subjects

A Zielke

Publications and source records attributed to A Zielke.

At least 19 recordsLinked to original sources

PubMed2006

Targeting the EGF/VEGF-R system by tyrosine-kinase inhibitors--a novel antiproliferative/antiangiogenic strategy in thyroid cancer.

AIM: In thyroid cancer (TC), endothelial growth factor (EGF) has been associated with dedifferentiation, tumor cell proliferation, and angiogenesis. Vascular endothelial growth factor (VEGF) has been documented to be the main stimulator of angiogenesis in the thyroid gland. Patients with undifferentiated thyroid cancer are in desperate need of new therapeutic strategies because common protocols of therapy usually fail. The aim of this study, therefore, was to evaluate two tyrosine-kinase inhibitors (TKI, ZD 1839 gefitinib and ZD 6474 vandetanib), directed against the EGF/VEGF receptor for possible antitumor therapy in thyroid cancer. METHODS: EGF/VEGF-R was documented in anaplastic (Hth74, C643), follicular (FTC133), and papillary (TPC1) thyroid cancer cell lines by Western blot analysis. The antiproliferative effect of two TKI (0.1-10 microM) on thyroid cancer cell lines in vitro was quantified by MTT assay, the antiangiogenic effect by assessing secretion of VEGF by enzyme-linked immunosorbent assay (R&D Systems). ZD 1839 is mainly directed against EGF-R and ZD 6474 against VEGF-R (AstraZeneca, UK), single applications and combinations of compounds were evaluated. RESULTS: EGF-R and VEGF-R as well as the phosphorylated receptor were documented in all of the cell lines. Administration of ZD1839 led to an up to 90% reduction of cell number in Hth74, 80% in C643, 50% in FTC133, and 90% in TPC1 (p < 0.05). ZD1839 induced a decrease of VEGF secretion between 30% in C643 and 90% in Hth74. Administration of ZD6474 led to an up to 95% reduction of cell number in Hth74, 85% in C643, 90% in FTC133, and 90% in TPC1 (p < 0.05). The ZD6474 induced decrease of VEGF secretion ranged between 20% (FTC133) and 60% (TPC1). Combinations of IC50 concentrations of TKI showed synergistic effects, resulting in additional inhibition of proliferation between 50 and 90% compared to single drug administration. CONCLUSION: The EGF/EGF-R system resembles a powerful VEGF-stimulating pathway in all histiotypes of TC and can be inhibited by TKI. TKI directed against EGF-R as well as VEGF-R inhibit tumor cell proliferation and VEGF secretion in vitro. Combinations of TKI are more effective than strategies using single agents. It is suggested that targeting EGF-R/VEGF-R-mediated pathways may have therapeutic potential in some undifferentiated thyroid cancers.

Carcinoma↗

PubMed2006

[The new role for endoscopic ultrasound in endocrinology: imaging of the adrenals and the endocrine pancreas].

Endoscopic ultrasound imaging of the adrenals and the endocrine pancreas enriches the diagnostic repertoire and improves the clinical opportunities of endocrinology. Its resolution enables detection of tumors as small as 2-3 mm. Endoscopic ultrasound imaging is especially relevant in the diagnosis of insulinomas and primary hyperaldosteronism, because it has direct consequences in planning a diagnostic and therapeutic strategy.

Adrenal Gland Diseases↗

PubMed2006

Negative stress-coping strategies among novices in surgery correlate with poor virtual laparoscopic performance.

BACKGROUND: This study explored the impact of habitual stress-coping strategies on the laparoscopic performance of novices in surgery using a virtual reality simulator. METHODS: The SVF78 stress-coping questionnaire was administered to 12 medical students in their final year of medical school (camera holders) and to 12 inexperienced surgical residents (postgraduate years 1-3). The questionnaire included devaluation during stressful situations, distractions from stressful situations, control over stressful reactions and negative coping strategies such as stress avoidance and need for social support. Assessment of laparoscopic dexterity was based on the results of performance on a virtual reality simulator. The variables of time taken to complete the task, errors and economy of motion were analysed, with a higher score indicating poor performance. Pearson and non-parametric Spearman correlations were used to compare the subjects' results on the SVF78 with those on the LapSim. RESULTS: Time taken to complete the task correlated with high values in distractive stress-coping strategies (P = 0.002) and high values in negative stress-coping strategies (P = 0.042). CONCLUSION: Ineffective stress-coping strategies correlate with poor virtual laparoscopic performance. The need for effective intraoperative stress-coping strategies is evident.

Adaptation, Psychological↗

PubMed2006

Antisense p53 decreases production of VEGF in follicular thyroid cancer cells.

Inactivating mutations of wild-type p53 (WTp53) tumor suppressor gene are common in anaplastic thyroid cancer (ATC) and are associated with poor prognosis. Mutated p53 (MTp53) has been implicated with angiogenesis. Therefore, the potential of MTp53 knockout by oligodeoxyribonucleotide phosphorothioates (ODNs) to affect VEGF production of undifferentiated thyroid cancer cells with a recessive MTp53 mutation was evaluated. Transient transfection with 20 bp ODNs complementary to portions of exon 10 of p53 and a negative control ODN (HIV-RT) were carried out in FTC-133 cells. In vitro secretion of VEGF protein was quantified by EIA and correlated to cell numbers, which was evaluated by in vitro MTT assay. Transfection of undifferentiated thyroid cancer cells with ODN reduced VEGF secretion of FTC-133 cells following transfection by 34% as compared to the negative control (cells transfected with ODN-HIV; p = 0.03). These results suggest that transient MTp53 knockout with ODNs complementary to p53 nucleotide sequences impair secretion of VEGF in the undifferentiated thyroid cancer cell line FTC-133.

Adenocarcinoma, Follicular↗

PubMed2006

Functional thyrotropin receptor attenuates malignant phenotype of follicular thyroid cancer cells.

Thyrotropin (TSH) is a thyroid-specific growth factor inducing differentiated function and growth of thyrocytes in vitro. In thyroid cancer, loss of TSH-receptor (TSHR) expression is a sign of de-differentiation and is believed to contribute to the malignant phenotype. The present studies aimed to determine the in vitro and in vivo effects of functioning TSHR in the follicular thyroid cancer cell line HTC, a subclone of FTC133 cells, lacking endogenous expression of TSHR, and HTCtshr+ cells transfected with human TSHR-cDNA. HTCtshr+ cells grew faster in vitro (doubling time 1.15 vs 1.56 d, p < 0.05) and TSH caused a dose-dependent growth response. Adhesion to and invasion through reconstituted basement membrane were reduced in HTCtshr+ cells, but when stimulated with TSH increased to levels comparable to naïve HTC cells. In vivo, tumor latency was 11 d for naïve HTC as compared to 21 d for HTCtshr+ xenografts. Smaller tumor volumes were registered for HTCtshr+ cells (250 +/- 217 vs 869 +/- 427 mm3, p < 0.05). Angiogenesis, as determined by vascular surface density (VSD) of experimental tumors, was enhanced in naïve HTC tumors (VSD 0.87 +/- 0.1 microm-1 vs 0.55 +/- 0.2 microm-1 in HTCtshr+, p < 0.05). VEGF secretion was more pronounced in naïve HTC cells stimulated with EGF, than in HTCtshr+ cells stimulated with either TSH or EGF. In conclusion, regained expression of functional TSHR in the follicular thyroid cancer cell line HTC alters in vitro features commonly associated with the malignant phenotype. Smaller tumors and reduced angiogenesis of xenotransplanted HTC cells with functioning TSHR suggest a less aggressive in vivo phenotype. The present data highlight the pivotal role of TSHR to affect transformed thyrocytes in vitro and in vivo. They also suggest a role for EGF as a modulator of angiogenesis in thyrocytes devoid of TSHR.

Adenocarcinoma, Follicular↗

PubMed2006

Analysis by cDNA microarrays of gene expression patterns of human adrenocortical tumors.

OBJECTIVES: Adrenocortical carcinoma (ACC) is a rare malignant neoplasm with extremely poor prognosis. The molecular mechanisms of adrenocortical tumorigenesis are still not well understood. The comparative analysis by cDNA microarrays of gene-expression patterns of benign and malignant adrenocortical tumors allows us to identify new tumor-suppressor genes and proto-oncogenes underlying adrenocortical tumorigenesis. DESIGN AND METHODS: Total RNA from fresh-frozen tissue of 10 ACC and 10 benign adrenocortical adenomas was isolated after histologic confirmation of neoplastic cellularity of at least 85%. The reference consisted of pooled RNA of 10 normal adrenal cortex samples. Amplified RNA of tumor and reference was used to synthesize Cy3- and Cy5-fluorescently labeled cDNA in a flip-color technique. D-chips containing 11 540 DNA spots were hybridized and scanned and the images were analyzed by ImaGene 3.0 software. RESULTS: The comparative analysis of gene expression revealed many genes with more than fourfold expression difference between ACC and normal tissue (42 genes), cortical adenoma and normal tissue (11 genes), and ACC and cortical adenoma (21 genes) respectively. As confirmed by real-time PCR, the IGF2 gene was significantly upregulated in ACCs versus cortical adenomas and normal cortical tissue. Genes that were downregulated in adrenocortical tumors included chromogranin B and early growth response factor 1. CONCLUSIONS: Comprehensive expression profiling of adrenocortical tumors by the cDNA microarray technique is a very powerful tool to elucidate the molecular steps associated with the tumorigenesis of these ill-defined neoplasms. To evaluate the role of identified genes, further detailed analyses, including correlation with clinical data, are required.

Adenoma↗

PubMed2006

Clinical background is required for optimum performance with a VR laparoscopy simulator.

OBJECTIVE: To determine the role of clinical background when assessing the learning effect using a virtual-reality (VR) laparoscopy simulator (LapSim). MATERIALS AND METHODS: Test subjects were 12 final-year medical students (Group A) and 12 inexperienced residents (Group B) with no previous experience of VR simulators. First, to establish a baseline, both groups performed the "clip application" task twice. They then completed a training program of increasing difficulty (coordination, cutting and clip application), after which both groups were re-tested using a difficult level of the "cutting" task as an endpoint measurement. Time to complete the tasks, as well as trauma and precision parameters, were scored. RESULTS: Before training, times to complete the baseline task, as well as parameters of trauma and precision, were similar for both groups. After training, Group B (residents) completed the cutting task significantly faster than Group A (students). However, the former group also showed significant improvement in trauma and precision parameter scores in the endpoint measurement. CONCLUSION: These results suggest that clinical background and understanding of the clinical value of a training program lead to faster acquisition and improvement of laparoscopic skills as performed on the laparoscopy simulator. Thus, medical students or other personnel not involved in practical surgery may be unsuitable as candidates for assessing the value of a VR training program.

Adult↗

PubMed2005

Successful treatment of solid-pseudopapillary tumor of the pancreas with multiple liver metastases.

The solid-pseudopapillary tumor (SPT) is a very rare pancreatic neoplasm that predominantly affects young females. About 450 cases have been described in the world literature and approximately 20% of the reported patients were children. The occurrence of SPT with distant metastases in children is extremely rare with only two previously reported cases. We now report a 16-year-old Asian girl with a large SPT and synchronous multiple liver metastases who was successfully treated in a 2-step strategy, including initial pylorus-preserving partial duodenopancreatectomy, right hemicolectomy, resection and allografting of the portal vein and secondary resection of 12 liver metastases. The patient is disease free after a follow-up of 18 months after resection of the primary tumor, suggesting that an aggressive surgical treatment might also be justified for metastasized SPT.

Adolescent↗

PubMed2005

[Minimal-invasive operative treatment of organic hyperinsulinism].

BACKGROUND: Insulinomas are small, solitary and benign endocrine pancreatic tumours, causing organic hyperinsulinism by autonomous insulin-secretion. Episodes of severe hypoglycemia and progressive obesity are the most frequent clinical signs. Surgical resection of the tumours is always indicated for cure. Because the tumours are small and surgical trauma for adequate exposure of the pancreas is considerable, laparoscopic techniques to approach these tumours are attractive. On the occasion of two cases, this report describes the laparoscopic treatment of these rare tumors. ANAMNESIS: Two male patients (15 years of age and 50 years of age) were admitted for seizures and symptoms of hypoglycaemia. FINDINGS: During fasting tests, both were diagnosed organic hyperinsulinism, with a blood glucose level of 28 mg/dl, insulin of 15.9 mU/ml and a c-peptide of 1.7 microg/l for an insulinogenic index of 0.57 determined in the young man. Similar values were obtained in the older man. Conventional imaging procedures were non diagnostic whereas endoscopic ultrasound of the pancreas revealed a 8 x 13 and 10 x 9 mm lesion in the pancreas. THERAPY AND COURSE: Laparoscopic resection of the tumor was attempted and accomplished in both patients. The young man underwent laparoscopic enucleation of the tumor, while the 50 year old man underwent left sided laparoscopic resection of the pancreas because the tumor was adjacent to the pancreatic duct. Postoperative course was uneventful in both cases. CONCLUSION: It is to be expected, that this approach will receive increasing attention in the near future.

Adolescent↗

PubMed2005

Conventional bilateral cervical exploration versus open minimally invasive parathyroidectomy under local anaesthesia for primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) has been introduced for the treatment of patients with primary hyperparathyroidism (pHPT). Thus far, only one randomized trial has compared video-assisted MIP with conventional bilateral cervical exploration (BCE). The value of open MIP is therefore not known. METHODS: Fifty patients with a solitary parathyroid adenoma localized before surgery by sestamibi scintigraphy were randomized to undergo BCE under general anaesthesia (n = 25) or targeted MIP via a 2-cm incision using local anaesthesia (n = 25). Postoperative hypocalcaemia was the primary endpoint. Secondary outcome measures were operating time, complications, postoperative analgesia and recurrent disease. Follow-up was carried out at 1 and 6 months. RESULTS: All patients who underwent BCE and 24 of those who had MIP were cured by the primary operation. Operating time was 22 min shorter in the MIP group (P = 0.024). Serum levels of calcium were slightly lower during the first 4 days after surgery in the BCE group (P = 0.022). No other no significant differences were found. CONCLUSION: Targeted MIP using local anaesthesia reduces operating time and causes less postoperative biochemical hypocalcaemia compared with bilateral neck exploration.

Adenoma↗

PubMed2005

[A virtual reality simulator for objective assessment of surgeons' laparoscopic skill].

BACKGROUND: The aim of this study was to validate computed virtual reality simulation as a tool to assess laparoscopic skills and to establish whether the simulator allows differentiating between surgeons with different laparoscopic experience. METHODS: 27 physicians at the surgical department of the University of Marburg, Germany, with different experience in laparoscopic surgery were divided into three groups: experienced (group I), intermediate (group II), and novices (group III). Following a brief introduction to the virtual reality simulator (LapSim), each participant performed twice a training program consisting of seven tasks (examinations I and II). RESULTS: Comparison of experienced surgeons with less experienced laparoscopic physicians showed a significant (P<0.05) superiority of group I at examinations I and II in most exercises. The groups' difference was more obvious in examination II, since the technique was new for all participants during examination I. Tasks of low complexity in virtual reality such as camera navigation, which are performed by young, not yet responsible surgeons in real surgery, did not show significantly different results between the three groups. CONCLUSION: Differences in laparoscopic experience can be visualised with a virtual reality simulator, and thus a simulator is helpful for assessing surgeons' laparoscopic skills.

Clinical Competence↗

PubMed2005

[Reoperation for primary hyperparathyroidism].

While the initial treatment for primary hyperparathyroidism (pHPT), if managed by an experienced surgeon, is almost always successful, reoperations are challenging. Patients are at high risk for complications and the rates of success are plainly below those of primary cervical explorations. In this paper the reasons for failure during initial procedures are reviewed, as are the most important localization procedures and the prerequisites with regard to technical infrastructure as well as personnel, when planning repeat operations for a missed parathyroid adenoma. Provided that a standardized diagnostic and surgical approach is used, the surgeon is experienced, and up-to-date technical equipment is available, permanent normocalcemia following reoperations in pHPT is more frequently achieved than it used to be. The best option to avoid reoperations and associated complications is a successful initial intervention by an experienced surgeon. However, reoperations should always be performed by an experienced surgeon.

Adenoma↗

PubMed2005

[Zollinger-Ellison syndrome].

The preoperative localization of gastrinomas often fails despite all modern imaging methods. Therefore, after biochemical confirmation of the diagnosis and exclusion of diffuse metastases, a meticulous surgical exploration including intraoperative ultrasound (IOUS) and duodenal exploration after duodenotomy should be performed. The experienced surgeon will be able to identify more than 90% of the primary tumors. Depending on the localization, excision of the tumor in the duodenal wall or enucleation from the pancreatic head should be performed. If the tumor is localized in the tail of the pancreas, distal pancreatectomy is the treatment of choice. Complete resection of the tumor is the only curative approach for the patients. For MEN-1 gastrinomas a spleen-preserving distal pancreatectomy with enucleation of tumors of the pancreatic head and duodenotomy with excision of duodenal gastrinomas should be performed. If the source of gastrin secretion can be regionalized to the pancreatic head by a preoperative SASI angiography, a pylorus-preserving partial pancreaticoduodenectomy might be the treatment of choice.

Adult↗

PubMed2005

Endoscopic ultrasound imaging of insulinomas: limitations and clinical relevance.

Compared to other imaging methods, endoscopic ultrasound is the best procedure to localize insulinomas preoperatively. Positive finding furthermore confirms endocrinological diagnosis, especially considering the differential diagnosis of hypoglycaemia factitia by oral antidiabetics. However, it always has to be considered that endoscopic ultrasound imaging may reveal false positive and false negative results, and quality of the findings obtained by endoscopic ultrasound imaging depends to a large extent on the examiner's experience. An important issue of endoscopic ultrasound imaging in insulinomas nowadays is planning surgical strategy. As illustrated by three cases, endoscopic ultrasound imaging enables to identify patients that qualify for laparoscopic, minimal invasive surgery.

Adolescent↗

PubMed2005

Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines.

Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially among the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (beta1-4, beta7, alpha1-6, alphaV, alphaIIb, alphaL, alphaM, alphaX) and of four IRM heterodimers (alpha2beta1, alpha5beta1, alphaVbeta3, alphaVbeta5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha2, alpha3, alpha5, beta1, beta3 and low levels of alpha1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha5 and beta1. ATC mainly displayed integrins alpha2, alpha3, alpha5, alpha6, beta1 and low levels of alpha1, alpha4 and alphaV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exceptions, namely alpha4, alpha6, and beta3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of thyroid tumor cell lines to ECM may not be associated with altered IRM expression.

Carcinoma↗

PubMed2005

An authentic malignant epithelioid hemangioendothelioma of the thyroid: a case report and review of the literature.

Hemangioendotheliomas of the thyroid are neoplasms that are rarely encountered in the Alpine region in Europe. The endemic goiter in this iodine-deficient region can be considered as a predisposing factor. We report the second case of an epithelioid hemangioendothelioma (EHE) of the thyroid gland and the first clinical case with malignant behavior. A 73-year-old woman with a long history of multinodular goiter presented with a rapidly growing thyroid mass, free of distant metastases. A total thyroidectomy was performed. Histologically the lesion had characteristic epithelioid and spindle cell proliferation in a background of chondromyxoid stroma. Cytoplasmic vacuolization in the epithelioid and spindle cells were present. Tumor cells were positive for factor VIII-related antigen, MNF116, PAN-ceratin, CD 34, and CD 31 and negative for cytokeratin allowing the diagnosis of EHE. Nine months after the primary resection the tumor locally recurred. A palliative resection was performed in a second operation followed by interferon-alpha therapy. The patient rapidly developed a second local relapse and died 13 months after the diagnosis of an EHE had been made. An improvement of the very poor prognosis of this rare tumor may depend on early tumor diagnosis and surgery combined with a multimodal treatment.

Aged↗

PubMed2004

[Diagnosis and surgical treatment of insulinoma--experiences in 40 cases].

BACKGROUND AND OBJECTIVE: Most insulinomas are solitary, benign and functional neuroendocrine pancreatic tumors which give rise to manifold symptoms. Their preoperative localization is often unclear, but the cure rate after their excision is very high. It was the aim of this study to analyse and evaluate our group of patients with regard to preoperative tumor localization and overall surgical results. METHODS: Data were collected as part of prospective observations and retrospective evaluation of all patients treated for insulinoma between 1987 and 2003 at the department of visceral- thoracic- and vascular surgery at the Philipps University of Marburg. In all of them the diagnosis had been confirmed by a fasting test. RESULTS: 40 patients with an insulinoma (22 females, 18 males; average age 52 years [range 12-87 years]) had been operated. The sensitivity of preoperative localization was 65% for endoscopic ultrasound, 33% for ultrasound, 33% for computed tomography, 15% for magnetic resonance imaging and 0% for somatostatin-receptor scintigraphy. But all insulinomas were identified intraoperatively by pancreas dissection and ultrasound (IOUS). 38 patients were completely cured by excision of the tumor. CONCLUSION: After positive biochemical and fasting tests and exclusion of diffuse abdominal metastases by transabdominal ultrasound, all patients should without further preoperative investigations undergo surgical excision of the insulinoma after bidigital palpation of the pancreas and IOUS. But if laparoscopic excision is planned, endoscopic ultrasound should be undertaken preoperatively.

Adolescent↗

PubMed2004

[Premedication visits. Economizing at the cost of the patient?].

The older the patient, the higher the risk of perioperative cardiac complications. Therefore, patients at risk have to be identified and the appropriate diagnostic or therapeutic measures initiated. The most important factor in this context is whether a planned surgery can be postponed. Several strategies have been developed (e.g. Goldman index, Eagle criteria) and the American Heart Association (AHA/ACC) has produced guidelines concerning perioperative diagnosis and therapy of cardiac risk patients. The common goal of these strategies is always the risk classification of the patient by combining the operative risk and the risk factors of the patient. The further procedure (diagnostic or therapeutic measures) is based on the risk classification. If further invasive therapy proves to be necessary, the determining factor is the period of time for which the operation can be delayed. This appears to be about 3 months but if this is not possible the outcome could be improved with a beta-blocker therapy in advance. A working group from the university hospital in Marburg has developed a strategy for risk classification and further diagnostic and therapeutic measures as outlined in this article.

Adrenergic beta-Antagonists↗