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H Dralle

Publications and source records attributed to H Dralle.

At least 91 records · Page 5Linked to original sources
PubMed2000

Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells.

Carcinoid tumors are predominantly found in the gastrointestinal tract and are characterized by hypersecretion of various substances, including bioamines and neuropeptides, leading to functional tumor disease. Here, we demonstrate that human BON carcinoid tumor cells express functionally active insulin-like growth factor-I (IGF-I) receptors and secrete IGF-I, suggesting an autocrine action of this growth factor. The IGF-I receptor was functionally active. IGF-I stimulated phosphatidylinositol 3-kinase (PI3-kinase), p70 S6 kinase (p70s6k), and extracellular signal-regulated kinase 2 activity in BON cells. Furthermore, immunoneutralization of endogenously released IGF-I markedly reduced the high basal activity of p70s6k and extracellular signal-regulated kinase 2 in serum-starved BON cells. Exogenously added IGF-I induced a marked increase in chromogranin A secretion, a marker protein for neuroendocrine secretion, by a process that was largely dependent on PI3-kinase activity. In addition, immunoneutralization of endogenously released IGF-I markedly reduced basal chromogranin A release by BON cells. Thus, the autocrine IGF-I loop regulates basal neuroendocrine secretion in BON cells. Next, we investigated the role of IGF-I as a growth promoting agent for BON cells. Our data demonstrate that IGF-I stimulates anchorage-dependent and anchorage-independent growth of BON cells by a pathway that involves PI3-kinase, mammalian target of rapamycin/p70s6k, and mitogen-activated protein kinase kinase 1 activity. Interestingly, mitogen-activated protein kinase kinase 1 activity was less important for anchorage-independent growth of BON cells. Endogenously released IGF-I was found to be largely responsible for autonomous growth of BON cells in serum-free medium and for the constitutive expression of cyclin D1 in these cells. In conclusion, IGF-I is a major autocrine regulator of neuroendocrine secretion and growth of human BON neuroendocrine tumor cells. Because our data also demonstrate that a significant proportion of neuroendocrine tumors express the IGF-I receptor and its ligand, interference with this pathway could be useful in the treatment of hypersecretion syndromes and growth of human neuroendocrine tumors.

Carcinoid Tumor↗
PubMed2000

Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis.

BACKGROUND: The aim of this study was to identify better prognostic parameters for normalization of serum calcitonin in medullary thyroid carcinoma (MTC) patients. METHODS: In 73 patients who had undergone systematic lymph node dissection for MTC between September 1995 and November 1998, preoperative (n = 29) and postoperative (n = 65) basal and stimulated serum calcitonin were correlated with the pTNM classification and the number of positive regional lymph nodes and compartments. RESULTS: In contrast to pT and M, there was a significant correlation between postoperative calcitonin and the pN category. With rising numbers of positive lymph nodes (0, 1-9, 10-19, and > or = 20), postoperative basal and stimulated calcitonin increased exponentially, and gross distant metastases (M1) occurred more frequently (0%, 4%, 13%, and 50%; P = 0.013). Conversely, serum calcitonin was less often normalized (65%, 31%, 0%, and 0%; P = 0. 003). There was a close correlation between the number of positive lymph nodes and the number of affected compartments (P < 0.001; r = 0.93). Irrespective of location, involvement of 10 or more lymph nodes and more than 2 compartments precluded normalization of serum calcitonin. CONCLUSIONS: Quantitative lymph node analysis of MTC improves prediction of calcitonin normalization. When more than two compartments are involved, normalization of serum calcitonin cannot be attained. Surgery should then be less extensive and more directed at preventing local complications.

Adult↗
PubMed2000

Sequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer.

To evaluate the involvement of hMSH6 in colorectal cancer, the complete coding sequence and flanking intron regions of the gene were analyzed by DNA sequencing in 10 patients fulfilling Bethesda Guidelines for colorectal tumors and 10 patients with sporadic colorectal carcinoma. In addition, 10 mono- and 10 dinucleotide repeat markers were analyzed for microsatellite instability. A protein-truncating T insertion at codon 218 was identified in the index person of a hereditary non-polyposis colorectal cancer (HNPCC)-like kindred and was accompanied by a somatic T deletion in the tumor. The tumor of this patient was positive for mono- but negative for dinucleotide repeat instability and lacked allelic losses at loci frequently affected in colorectal carcinomas. A novel amino acid change, F340S, was found in a patient with sporadic colon and breast cancer and leukemia but was not detected in 246 chromosomes from healthy anonymous blood donors. In addition, we describe 2 silent and 15 intronic sequence variants not previously reported. Although the frequency is low, we present further evidence for hMSH6 germline mutations that predispose patients to HNPCC-like phenotypes and suggest that mono- and dinucleotide repeat instability testing may be useful for distinguishing between individuals harboring an hMSH2 or hMLH1 mutation and a mutation of the hMSH6 gene.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Endocrine surgery and evidence-based medicine].

INTRODUCTION: The aim of this literature review is to classify current knowledge on nine questions of current interest for endocrine surgery and their classification with regard to levels of evidenced-based medicine (EBM). METHODS: The literature in Medline and EMBase was reviewed. Only retrospective or prospective comparative studies with statistical analysis were selected. RESULTS: (See Table 8.). CONCLUSION: With respect to the current literature, only routine identification of the RLN and the minimally-invasive approach for adrenalectomy can be regarded as EBM. To answer the remaining questions prospective studies are needed.

Adrenal Glands↗
PubMed2000

[Use of the heart-lung machine in extra-cardial carcinoma surgery].

The employment of the heart-lung machine to assisting the circulatory system for the resection of extracardial tumors is increasing because of their location, growth and infiltration. We report on three patients in whom the resection of the tumor was only possible with extracorporeal circulation (ECC). In the first patient sarcoma of the pulmonary artery and valve was resected under ECC. Artery and valve were replaced with a cryo-preserved valved bifurcation homograft. In the other patients ECC was used on the basis of tumorinfiltration of the inferior vena cava and tumor embolus of the pulmonary artery in a case of primary renal cell carcinoma, and tumor infiltration of the superior vena cava and right atrium in a case of follicular thyroid carcinoma. All patients had a good postoperative course and excellent long term survival.

Adenocarcinoma, Follicular↗
PubMed2000

[Delayed diagnosis of odontoid fracture after whiplash trauma of the cervical spine].

Fractures of the odontoid process represent about 10-20% of all diagnosed cervical spine fractures. Approximately 35% of these fractures are classified as Type II according to Anderson and D'Alonzo. They can be potentially unstable especially if combined with a dens displacement of over 6 mm. In severe cervical spine trauma, these fractures do not usually cause difficulties in diagnosis. However, in whiplash injuries, which are very common and only rarely associated with such fractures, the surgical management can be complicated if they are underestimated. These patients can present without significant neurological deficits or the situation can be complicated due to intoxication or additional trauma. Under these circumstances in particular, the diagnosis can be delayed or missed, if no strict protocols for diagnostic effort in all whiplash injuries are employed. A case of delayed diagnosis of an odontoid fracture in a neurological asymptomatic patient after whiplash injury is presented.

Adult↗
PubMed2000

Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany.

Risk factors for postoperative complications of benign goiter surgery have not been investigated systematically. To this end, a prospective multicenter study (January 1 through December 31, 1998) was conducted involving 7266 patients with surgery for benign goiter from 45 East German hospitals. High-volume providers (>150 operations per year) performed 69% (5042/7266), intermediate-volume providers 27% (50-150), and low-volume providers 4% (258/7266) of operations. Among the hospital groups, the pattern of thyroid disease did not vary significantly, but there was a trend that small-volume providers tended to perform more operations for uninodular goiter and high-volume providers treated more patients with Graves' disease and recurrent goiter. Extent of resection (p < 0.0001) and remnant size (multinodular goiter and recurrent goiter, p < 0.001), differed significantly, with total thyroidectomy being performed more often in hospitals with more than 150 operations compared to hospitals with an operative volume of less than 150 procedures per year. Despite the larger extent of resection and smaller remnant size, rates of recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism were not increased. When the logistic regression analyses were fitted to evaluate the impact of risk factors on transient and permanent RLN palsy and hypoparathyroidism, larger extent of resection [relative risk (RR) 1.5-2.1] and recurrent goiter (RR 1.8-3.4) consistently evolved as independent risk factors. With hypoparathyroidism, additional significant factors included patient gender (RR 2.1-2.4), hospital operative volume (RR 0.8-1.5), and Graves' disease (RR 2.8). Unlike parathyroid gland identification during hypoparathyroidism, RLN identification (RR 1.6) significantly (p = 0.01) reduced permanent RLN palsy rates. The multivariate analyses clearly confirmed the pivotal role of routine RLN identification, independent of the extent of the thyroid resection. These findings might help hospitals with lower operative volumes to identify patients at increased risk whom they might consider for specialist care.

Adult↗
PubMed2000

Differential diagnosis of calcitonin-secreting neuroendocrine carcinoma of the foregut by pentagastrin stimulation.

BACKGROUND AND AIMS: This study assessed the suitability of pentagastrin stimulation in hypercalcitoninaemia for differential diagnosis of neuroendocrine carcinoma of the foregut. PATIENTS: A prospective institutional study (March 1997-September 1999) was conducted involving all patients admitted to the pneumological and general surgical wards for small cell lung cancer (SCLC) or primary medullary thyroid carcinoma (MTC). Basal and stimulated serum calcitonin levels were measured using an improved immunoradiometrical assay for the monomeric form of calcitonin. RESULTS: Increased basal calcitonin levels were noted in six non-MTC patients (one mediastinal and one laryngeal neuroendocrine carcinoma, and four SCLCs). Because of chronic renal failure, one SCLC patient had to be excluded. The remaining five non-MTC patients with normal renal function were compared to eight primary MTC patients. In terms of pentagastrin stimulation, an increase in serum calcitonin levels of less than twofold the baseline significantly correlated with both non-MTC (r=0.85; P=0.005) and SCLC (r=0.81; P=0.024). Immunostaining of tissue specimens for calcitonin was positive in the patients with mediastinal and laryngeal neuroendocrine carcinoma and in all eight patients with primary MTC, but was negative in the two SCLC patients with adequate tissue samples. CONCLUSIONS: Irrespective of the pathophysiological background, pentagastrin stimulation affords a differential diagnosis in neuroendocrine carcinoma of the foregut when chronic renal failure is excluded.

Aged↗
PubMed2000

Unilateral open and minimally invasive procedures for primary hyperparathyroidism: a review of selective approaches.

The currently established procedure for surgical treatment of primary hyperparathyroidism is bilateral exploration and visualization of all four glands to identify an adenoma and exclude multiglandular disease. With the development of improved preoperative localization imaging of the parathyroids using high-resolution ultrasonography and sestamibi scintigraphy, on the one hand, and perioperative control of surgical success with a rapid parathyroid hormone assay on the other, unilateral and minimally invasive techniques have become feasible. For patients with unequivocal localization in preoperative sestamibi scintigraphy and high-resolution ultrasonography of the parathyroid adenoma in probable single-gland disease, the unilateral and minimally invasive parathyroidectomy present a therapeutic option. Perioperative rapid parathyroid hormone assays, although costly, offer immediate supervision of adenoma extirpation and differentiation of single- and multiglandular disease. These methods demonstrate advantages with favorable cosmetic results and lower reported rate of postoperative hypoparathyroidism. These methods are already being practiced in some places under local anesthesia and in an ambulatory setting. This contribution provides an introduction and overview of the currently practiced unilateral and minimally invasive techniques of parathyroidectomy for primary hyperparathyroidism, discussing indications, advantages and disadvantages, and technical differences in the practiced methods.

Humans↗
PubMed2000

Regulation of proliferation and apoptosis in sporadic and hereditary medullary thyroid carcinomas and their putative precursor lesions.

C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients affected by germline mutations of the RET oncogene represent an exceptional opportunity to study the regulation of proliferation and apoptosis during tumour initiation and progression. In 56 specimens [CCH, n=1; MTC with CCH, n=26; MTC, n=20; lymph-node metastasis (LNM), n=9] from 46 patients [multiple endocrine neoplasia type 2a (MEN2a), n=24; MEN2b, n=2; familiar MTC (FMTC), n=4; sporadic MTC, n-16] and 3 cases of non-neoplastic CCH, proliferation activity (MIB1), the rate of apoptosis [dUTP nick end labelling (TUNEL)] and expression of p53, bcl-2, bcl-x and bax were investigated and compared with clinical data. In MEN-associated CCH and small MTC, bcl-2 was strongly expressed, bcl-x was moderately expressed and bax was only weakly expressed. Advanced tumours and LNM did show a more heterogeneous bcl-2 staining accompanied by an increased bax expression and accelerated proliferation. The rate of apoptosis was extremely low in all investigated tumours. P53 was detectable in three patients with rapidly growing and extensively metastasising MTC. No somatic p53 mutations were found. Hereditary MTC with germline RET mutations at codon 918 (MEN2b) and codon 634 revealed a bias towards a higher proliferation activity at a younger age and are more frequently accompanied by LNM. CCH and MTC are characterised with a preponderance of bcl-2 as a factor blocking the programmed cell death. While MTC, in general, is a slowly growing tumour, a minority of tumours do progress rapidly with high proliferation. The factors leading to an accelerated tumour progression do not seem to take their effect via the regulation of apoptosis. Certain alterations of RET are supposed to have a direct or indirect implication on proliferation and, because of this, an effect on the clinical course.

Adolescent↗
PubMed2000

Aberrations of chromosomes 5 and 8 as recurrent cytogenetic events in anaplastic carcinoma of the thyroid as detected by fluorescence in situ hybridisation and comparative genomic hybridisation.

Comparative genomic hybridisation (CGH) is a technique which identifies gains and losses of DNA sequence copy number in tumours. We used CGH to search for genetic changes in one of the most aggressive malignancies--anaplastic thyroid carcinoma (ATC). For this purpose, we analysed tumour specimens of nine ATCs and DNA of two ATC cell lines. CGH detected aberrations in 10 of 11 samples, with a mean number of gains or losses per carcinoma of 4.8 (range 0-13). Total or partial changes of chromosome 8 (n=6), including gains or losses of 8p (n=6) or 8q (n=5) were those detected most frequently. Chromosome 5p was amplified in five cases. Gains in two of three samples were found for 3q, 7p, 11q and 20q. Gains in a fewer number were seen for 1p (1 case), 1q (1), 7q (2), 9q (2), 11p (2), 12q (1), 14 (1), 15 (1), 17q (2), 18p (2), 18q (1), 20p (1), 21 (2), Xp (2) and Xq (2). Losses were less frequent than gains and observed for 1p (2 cases), 1q (1), 2p (1), 2q (2), 3p (2), 3q (1), 4q (2), 6q (1), 9p (2), 9q (1), 18p (1), 18q (1) and Y (2). Examples of analysis of tumour sections and cell lines performed by fluorescence in situ hybridisation (FISH) confirmed the gains and losses found by CGH and detected additional signals for 8q21 in tumour cells in a sample with no gains or losses normally in CGH. The results suggest that aberrations of 5p, 8p and 8q, which are rarely found in differentiated thyroid carcinoma, may play an important role in the development of ATC. Therefore, these chromosomes could harbour gene loci potentially involved in the aggressiveness of neoplastic tumours, as shown in tumours such as in this study for ATC.

Adult↗
PubMed2000

Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors.

Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.

Cell Nucleus↗
PubMed2000

Simultaneously occurring liver metastases of pheochromocytoma and medullary thyroid carcinoma--a diagnostic pitfall with clinical implications for patients with multiple endocrine neoplasia type 2a.

Malignant pheochromocytoma is an exceptional complication in patients with Multiple Endocrine Neoplasia Type 2a (MEN2a). In this paper, we report on a 53-year-old male patient with an evident RET gene germline mutation, who simultaneously developed hepatic metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma. Comprehensive immunohistochemical investigations were performed to elaborate markers which could be useful for differentiating between MTC metastases and pheochromocytoma, respectively. Calcitonin and CEA, in particular cytokeratins and trefoil factor family 1 (TFF1), were detectable exclusively in MTC, whereas all the other markers revealed a comparable expression in both MTC and pheochromocytoma. The only clues that could indicate a potential malignant course were size, a lack of sustentacular cells and hyaline globules, and a focal spindle cell pattern in pheochromocytoma. Owing to a wide agreement in cellular differentiation and a lack of specific, routinely applicable markers for pheochromocytomas, a comprehensive and goal-directed immunohistochemistry is required to rule out pheochromocytoma metastasis in patients with MEN2a. A misinterpretation could lead to harmful clinical complications, as shown in the present case.

Adrenal Gland Neoplasms↗
PubMed2000

Concepts for screening and diagnostic follow-up in multiple endocrine neoplasia type 1 (MEN1).

The recent identification of MEN1 gene mutations as the molecular cause of familial multiple endocrine neoplasia type 1 syndrome (MEN1) has had a significant impact on clinical patient care. In the following consensus statement we will present recommendations for clinical screening and follow-up in patients and relatives with suspected or established MEN1 syndrome. MEN1 mutational analysis should be performed in individuals with newly diagnosed MEN1-typical endocrine neoplasia (e.g., primary hyperparathyroidism, gastroenteropancreatic tumor, pituitary adenoma) if additional diagnostic criteria are met (e.g., age <40 years; positive family history; multifocal or recurrent neoplasia; two or more organ systems affected). Genetic family screening is advisable in first degree relatives of MEN1 patients during early adolescence to reliably assess future MEN1 disease risk. In symptomatic individuals carrying MEN1 germ line mutations, annual clinical and biochemical (calcium, PTH, gastrin, prolactin) follow-up as well as routine pancreatic and pituitary imaging may be complemented as individually needed. In contrast, relatives without family-specific MEN1 mutation do not require routine follow-up. Diagnostic procedures and treatment in symptomatic MEN1 mutation carriers and patients may differ from that in sporadic endocrine neoplasia, calling for individual management. Genetic counselling and dedicated endocrine surgery should be integral parts of current medical care in MEN1 syndrome.

Genetic Testing↗
PubMed2000

Hypercalcitoninemia in a sporadic asymptomatic neuroendocrine tumor of the pancreatic tail.

BACKGROUND/AIM: Asymptomatic neuroendocrine tumors of the gastroenteropancreatic tract represent a significant challenge in terms of postoperative monitoring. METHODS: A case report of a calcitonin-secreting asymptomatic neuroendocrine tumor of the pancreatic tail is presented. RESULTS: Hypercalcitoninemia was noted in the 76-year-old Caucasian man who had a recurrent neuroendocrine tumor of the pancreatic tail. Upon pentagastrin stimulation, basal calcitonin increased only moderately from 82.3 (<10) to 100.9 and 125 pg/ml after 2 and 5 min, respectively. Surgical removal of the neuroendocrine tumor resulted in postoperative normalization of both basal and stimulated serum calcitonin levels. On immunohistochemistry, the neuroendocrine tumor was positive for calcitonin. CONCLUSION: Routine measurements of serum calcitonin might be a highly sensitive adjunct capable of identifying a subset of neuroendocrine tumors in which calcitonin monitoring may aid in the early detection of postoperative recurrence.

Adenoma, Islet Cell↗
PubMed2000

Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region.

Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.

Adenoma↗