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Biomedical subjects

H Dralle

Publications and source records attributed to H Dralle.

At least 19 recordsLinked to original sources
PubMed2006

Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions.

BACKGROUND: Patients with a multiple endocrine neoplasia type 1 (MEN1)-associated Zollinger-Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions. AIMS: To test these lesions for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13, and to investigate whether the MEN1-related endocrine cell changes also involved somatostatin cells. MATERIAL AND METHODS: Tissue specimens from six patients with MEN1 and ZES were analysed by immunohistochemistry and immunofluorescence. LOH analysis was performed by fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene locus and the centromere 11 (C11) region. For simultaneous analysis of hormones and allelic deletions, a combined FISH/immunofluorescence protocol was established. RESULTS: 28 of a total of 33 duodenal neuroendocrine tumours (NETs) were gastrin-producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. Five of the NETs were somatostatin-expressing tumours, two revealing LOH. Allelic loss was detected in tumours as small as 300 microm (gastrin) and 400 microm (somatostatin) in diameter. The gastrin-producing tumours showed different deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to those of the gastrin cells, were present in all patients. The hyperplastic lesions of both cell lines consistently retained both 11q13 alleles. CONCLUSIONS: Allelic deletion of the MEN1 gene may reflect a pivotal event in the development of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients with MEN1. The observation of distinct deletion patterns in small synchronous tumours supports the concept that each gastrin-producing tumour in an individual MEN1 patient arises from an independent cell clone.

Adult↗
PubMed2006

[Prophylactic parathyroidectomy for familial parathyroid carcinoma].

In contrast to primary hyperparathyroidism, parathyroid carcinoma is a rare disease. In patients with hyperparathyroidism jaw tumor (HPT-JT) syndrome, caused by germline mutations in HRPT2, the development of parathyroid carcinoma is estimated to be 10-15%. This review summarizes the clinical and molecular genetic data of about 100 patients in the literature and three of our own cases. Unfortunately, osteofibromas, which might enable timely diagnosis of HPT-JT syndrome, occur in only about 30% of patients; about 80% have uniglandular disease. Based on the current data, a general recommendation to perform prophylactic parathyroidectomy cannot be given. However, thorough screening of patients at risk is mandatory. Of note in patients thought to have sporadic parathyroid carcinoma, germline HRPT2 mutations are found in up to 20%. Hence, any patient with parathyroid carcinoma should undergo HRPT2 mutation analysis.

DNA Mutational Analysis↗
PubMed2006

Cytology and mRNA expression analysis of fine needle aspirates of thyroid nodules in an East German region with borderline iodine deficiency.

Fine needle aspiration cytology (FNAC) is widely recommended as an important tool for pre-operative identification of malignancy in patients with nodular thyroid disease. To assess the diagnostic contribution of FNAC and the potential of quantitative mRNA analysis in fine needle aspirates in daily practice, we conducted a prospective study in thyroid clinics (n=2) and endocrine practices (n=3), respectively in an East German region with borderline iodine deficiency. Two-hundred and forty-four consecutive FNACs were obtained over a period of 2 years (2002-2004) from euthyroid patients presenting for first evaluation of a solitary thyroid nodule. The mean nodule size for FNAC was 27 mm (range: 10-79 mm). In 55% of patients FNAC was performed after scintiscan detection of a cold or normal functioning thyroid nodule (CTN), while in the remainder FNAC was performed as a primary investigation. FNAC outcomes were: 57.8% benign, 22.1% indeterminate, 2.5% suspicious for malignancy, 17.6% non-diagnostic. Messenger RNA levels for a house keeping gene (beta-actin) and a thyroid specific marker (thyroglobulin, Tg) were studied as basic molecular markers using real-time PCR. Both in the IN VIVO and EX VIVO FNA series, beta-actin and Tg mRNA levels were positively correlated with the thyrocyte cell yield/respective FNA smear. However, subgroup analysis showed that FNAC with histologically confirmed follicular thyroid cancer and/or microfollicular adenoma exhibited significantly lower Tg mRNA expression despite high beta-actin levels. Sufficient mRNA quantities were obtained in >90% of FNA specimen to allow quantitative mRNA analysis of at least 5 further genes. In conclusion, quantitative mRNA analysis is feasible in FNA on a routine basis and provides a perspective for a molecular distinction of thyroid nodules, once specific marker genes have been defined for benign and malignant thyroid tumours respectively.

Actins↗
PubMed2006

[Therapy and course of disease in spontaneous esophageal perforations].

INTRODUCTION: Esophageal perforations occur spontaneously or as a complication of endoscopic procedures. Especially in spontaneous perforation there is ongoing debate regarding the best treatment options. METHODS: 24 patients that were treated at two surgical centers (University Halle, City-hospital Bielefeld) after spontaneous esophageal perforations between 1996 and 2005 were analysed retrospectively. RESULTS: All patients but one underwent surgical treatment with in 2 cases additional stent implantation. Average stay in hospital was 53 days. In-hospital-lethality was 25% (overall lethality 37.5%). Concerning the therapeutic outcome there was no link between patients' age, localization or size of the perforation and the time interval between perforation and treatment. In 22 patients diagnosis was made > 12hrs after the event. CONCLUSIONS: Main problem of the Boerhaave-syndrome is the septic-toxic disease. Prognostic criteria are the patients' health-state and not factors like size of perforation, time of delay or localization of the perforation. Since in case of survival esophageal resection shows good long-term-results, in doubt a radical surgical procedure should be recommended as primary option. Implanting an esophageal stent might become a useful mean of treating patients with spontaneous perforations.

Adult↗
PubMed2006

Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype.

OBJECTIVE: In children with RET proto-oncogene mutation, curative treatment of medullary thyroid carcinoma (MTC) is possible by prophylactic thyroidectomy. Recommendations on the timing and extent of thyroidectomy are based upon a model that utilises genotype-phenotype correlations to stratify mutations into three risk groups. DESIGN: We evaluated the long-term outcome (mean follow-up 6.4 years, 15 patients more than 10 years, 26 patients more than 5 years) of operated gene carriers stratified into two risk groups (levels 1 and 2) based on the biological aggressiveness of MTC. RESULTS: In 46 RET gene carriers, prophylactic thyroidectomy was carried out between the ages of 4 and 21 years. Level 1 mutations were harboured by 11 patients (codons 790, 791, 804 and 891). Histology was completely normal in two patients; in seven patients C-cell hyperplasia (CCH) and in two patients T1 tumours were diagnosed. All patients with level 1 mutations were cured. Level 2 mutations were harboured by 35 patients (codons 618, 620, 630 and 634). Histology of these patients showed CCH in 11 patients, T1 tumours in 21, T2 tumour in 1, T3 tumour in 1 and Tx in 1 patient. Histology showed no lymph node involvement. Five patients with level 2 mutations failed to be cured; in two patients, persistence of MTC was diagnosed directly after thyroidectomy and in three during follow-up. In two patients carrying a 634 mutation, other endocrinopathies (hyperparathyroidism and bilateral pheochromocytoma) manifested during follow-up. CONCLUSIONS: If prophylactic thyroidectomy is done at early ages, cure rate is high. Timing and extent of prophylactic thyroidectomy can be modified by individual RET mutation.

Adolescent↗
PubMed2005

25-hydroxyvitamin D3 1alpha-hydroxylase and vitamin D receptor expression in papillary thyroid carcinoma.

Vitamin D receptor (VDR) and 25-hydroxyvitamin D3 1-alpha-hydroxylase expression have recently been shown to be upregulated in several tumors and thought to represent an important endogenous response to tumor progression. Little is known about the expression of these proteins in thyroid carcinoma, although previous reports have documented evidence of the biological effect of vitamin D in thyroid cells. Using paraffin-embedded and frozen sections of papillary thyroid carcinoma, we utilized real-time quantitative RT-PCR and immunohistochemistry to characterize the expression of VDR and 1-alpha-hydroxylase in thyroid follicular cells, with special emphasis on papillary thyroid carcinoma (PTC). VDR and 1-alpha-hydroxylase expression were increased in PTC compared with normal thyroid tissue and especially high in areas of lymphocyte infiltration. Expression of VDR and 1-alpha-hydroxylase in PTC may be compatible with an overall favorable prognosis for this tumor type and may constitute important prerequisites for using vitamin D and/or vitamin D analogs in the treatment of PTC.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2005

Insufficiency risk of esophagojejunal anastomosis after total abdominal gastrectomy for gastric carcinoma.

BACKGROUND: The outcome and quality of surgical treatment in gastric cancer are closely associated with specific postoperative morbidity and mortality, in addition to an oncosurgically adequate resection status. In this context, a preventive concept of decreasing the insufficiency rate of esophageal anastomosis may have a great impact. METHOD: Over a time period of 12 months (from 1 January 2002 to 31 December 2002), 1,199 patients (from 80 East German hospitals) with gastric carcinoma, carcinoma of the esophagogastral junction, or gastrointestinal stroma tumor (GIST) were enrolled in this prospective multicenter observational study with the aim of evaluating their early postoperative outcome. By means of a logistic regression analysis, independent variables, which alter significantly the healing of esophagojejunal anastomosis, were determined; in addition, their clinical impact on preventive management to lower the insufficiency rate of esophageal anastomosis was investigated. RESULTS: In 1,139 patients, histological investigation revealed gastric carcinoma. Out of these patients, 1,031 subjects underwent surgical intervention (90.5%) and 891 individuals underwent resection (86.4%). In 813 patients, radical resection (subtotal resection and gastrectomy) was executed (78.9%), whereas in 726 cases, R(0) resection was achieved (81.5%). Gastrectomy was the preferred procedure in 649 patients, resulting in a gastrectomy rate of 62.9% relating to all patients who underwent operation (curative and palliative intention, 80.3% and 19.7%, respectively). The insufficiency rate of esophagojejunal anastomosis was 5.7% (37/649). Neither the comparison between the various procedures for the reconstruction of the esophagojejunal passage and anastomosing techniques after gastrectomy nor that between gastrectomies with curative and palliative intention revealed any significant difference. Dysphagia and gastric outlet syndrome due to a stenosis were determined as independent variables by a logistic regression analysis of all preoperative and intraoperative variables. In all patients with gastric carcinoma, both parameters were recorded in 9.9% (113/1,139) and 6.7% (76/1,139), respectively. CONCLUSION: Dysphagia and gastric stenosis, which significantly influence the healing of esophagojejunal anastomosis after gastrectomy, are considered characteristics of an advanced tumor growth and a pretherapeutic lack of an adequate nutrition. This emphasizes the necessity of an early diagnosis of gastric cancer in order to lower perioperative morbidity. In addition, dysphagia is commonly associated with an obstruction of the upper gastrointestinal tract, which can lead to nutritional deficits, and thus deserves specific care during preventive management.

Adolescent↗
PubMed2005

[Recurrent operations on the adrenal glands].

Repeat adrenalectomy may be required due to ipsilateral recurrence of benign or malignant adrenal tumors after previous total or subtotal adrenalectomy. Even for multivisceral resection in patients with adrenocortical carcinoma, complete resection of local recurrent tumor offers results similar to those of primary resection (5-year survival 40-60%). In contrast, since no benefit on long-term survival has been shown so far by tumor debulking, palliative tumor resection should only be performed individually for control of severe endocrine symptoms. The effect of endoscopic adrenalectomy in patients with large tumors (>5 cm) or suspected malignancy has still not been well examined. Further studies are required. In any case, during open or endoscopic approach, tumor spillage must be avoided to prevent local tumor cell implantation. Following subtotal adrenalectomy, the risk of ipsilateral recurrence correlates with disease, follow-up, localization, size of the adrenal remnant, and, in case of familial pheochromocytoma, probably with genotype.

3-Iodobenzylguanidine↗
PubMed2005

Frequent promoter methylation of tumor-related genes in sporadic and men2-associated pheochromocytomas.

Hypermethylation of CpG island promoters is associated with transcriptional inactivation of tumor suppressor genes in neoplasia. Inactivation of p16 and Pten was related to the development of pheochromocytomas. In this report, we investigated the methylation status of the p16INK4a cell cycle inhibitor gene and other prominent tumor-related genes ( PTEN, RASSF1 A, CDH1, MSH2, MLH1, VHL, and TIMP3) in sporadic and multiple endocrine neoplasia type 2 (MEN2) pheochromocytomas by methylation-specific PCR. Hypermethylation was detected in 48 % of pheochromocytomas for RASSF1 A, 24 % for p16, 36 % for MSH2, 16 % for CDH1, and 8 % for PTEN. No VHL, MLH1, and TIMP3 methylation was observed. Interestingly, the frequency of p16 inactivation in familial tumors was higher (5 out of 12, 42 %) than in sporadic tumors (1 out of 13, 8 %; p = 0.047) and RASSF1 A inactivation was more common in the hereditary tumors (58 %) compared to the sporadic tumors (38 %). Combined methylation of RASSF1 A and p16 was found only in MEN2-related pheochromocytomas. Thus, a subset of hereditary pheochromocytomas displays preferential methylation of p16 and RASSF1 A.

Adrenal Gland Neoplasms↗
PubMed2005

[Thyroid surgery: generalist or specialist?].

BACKGROUND: Thyroid surgery is done in Germany in a considerable numbers of operations (about 110,000 per year). To perform thyroid operations by so called "generalists" or "specialists" have been discussed intensively, however, this issue have not been analyzed in detail. METHODS: Study material comprised 16,500 consecutive thyroid operations with 30,000 operated sites that have been prospectively documented in the German Thyroid Multicenter Study performed 1998 through 2001. Quality of surgery were analyzed by calculating the inverse relationship between volume and outcome (complication rate). RESULTS: To achieve complication rates (permanent unilateral recurrent laryngeal nerve paralysis and hypocalcemia) of < 1 % (primary surgery) or < 3 % (redo surgery) the minimum number of thyroid operations of lower level of experience (e. g. benign nodular goiter) per year was n=30. The minimum number of operations with higher level of experience was significantly lower (n=3-12) due to the higher level of experience of operating surgeons. In contrast to the rates of postoperative hypocalcemia the rates of postoperative recurrent laryngeal nerve paralysis was clearly related to the number of thyroid operations performed. CONCLUSIONS: The high number of thyroid operations in Germany with about 20 % of operations of high level experience are requiring surgical curricula and hospital structures that offer as well generalists as specialists to treat the broad spectrum of thyroid diseases accordingly. To lower the complication rate especially of difficult thyroid operations the level of specialization in Germany have to be increased.

Clinical Competence↗
PubMed2005

Evaluation of peroxisome proliferator-activated receptor-gamma expression in benign and malignant thyroid pathologies.

Impairment of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) function through a dominant negative PAX-8/PPAR-gamma fusion gene or other events resulting in wild-type PPAR-gamma downregulation has been implicated in malignant thyroid cell transformation. The aim of our study was to perform a systematic evaluation of PPAR-gamma mRNA and protein expression in normal thyroid tissue as opposed to benign thyroid pathologies of different functional status and thyroid malignancy, to gain further insights into a putative physiological role of PPAR-gamma in the thyroid and to define whether PPAR-gamma could serve as a marker of thyroid cell differentiation. Ten cold benign (CTN) and 10 toxic (TTN) thyroid nodules and corresponding normal thyroid tissues, 10 follicular thyroid cancers (FTC), 10 papillary thyroid cancers (PTC) and 8 Graves' disease (GD) thyroids were studied by real-time polymerase chain reaction (PCR), immunohistochemistry and reverse transcriptase (RT)-PCR (PAX-8/PPAR-gamma fusion gene). PPAR-gamma mRNA expression was demonstrated in all samples. When comparing benign nodular and normal thyroid tissue of the same patient no significant difference in PPAR-gamma mRNA expression was observed. PPAR-gamma mRNA levels were similar in CTN and FTC. In contrast, PPAR-gamma mRNA expression was downregulated in 9 of 10 PTC and all GD samples, whereby at least 4 fold downregulation (compared with normal and benign nodular thyroid tissues) was observed in the latter. Immunohistochemistry showed an increased, patchy PPAR-gamma nuclear staining in CTNs and TTNs and only faint staining in the corresponding normal thyroid tissues. A diffuse and weak PPAR-gamma staining pattern was observed in all GD samples. No PAX-8/PPAR-gamma rearrangements were detected in any of the 68 thyroid tissue samples. In conclusion PPAR-gamma mRNA and protein expression levels are not concordant in benign thyroid nodular disease. Furthermore there is no clear-cut association of PPAR-gamma mRNA expression with follicular thyroid tumorigenesis. Absence of a PAX-8/PPAR-gamma fusion gene in the series of 68 thyroid samples is in agreement with the suggestion of PAX-8/PPAR-gamma rearrangement being restricted to a subset of follicular thyroid cancers. The marked downregulation of PPAR-gamma in GD warrants further investigation and could be linked, for example, with changes in apoptosis.

Adenoma↗
PubMed2005

Advances in the management of hereditary medullary thyroid cancer.

This work draws on recent advances during the era of codon-oriented prophylactic surgery for hereditary medullary thyroid cancer (MTC). Milestones included identification of RET (REarranged during Transfection) as the susceptibility gene, introduction of prophylactic surgery on evidence of a RET germline mutation, revelation of genotype-phenotype correlations within the MEN 2 spectrum and demonstration of age-related progression of MTC. Novel surgical techniques, notably systemic microdissection and compartment-oriented surgery, have greatly enhanced surgical cure. Uncovering molecular pathways from RET genotype to MEN 2 phenotype should provide treatment options for RET mutation carriers whose MTC currently is too advanced for cure.

Age Factors↗
PubMed2005

Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours.

OBJECTIVE: We evaluated three markers (insulin-like growth factor II (IGF-II), cyclooxygenase-2 (COX-2) and ets-1) of thyroid growth stimulation and cell transformation together with a thyroid-specific marker (thyroglobulin (Tg)) for their potential to differentiate benign and malignant follicular thyroid neoplasia (FN). DESIGN AND METHODS: mRNA expression levels were determined by real-time PCR in 100 snap-frozen thyroid samples: 36 benign thyroid nodules with different histology and function (19 cold (CTN) and 17 toxic thyroid nodules (TTN)), 36 corresponding normal thyroid tissues of the same patients, eight Graves' disease (GD) thyroids, 10 follicular thyroid carcinomas (FTC) and 10 papillary thyroid carcinomas (PTC). RESULTS: Mean IGF-II and COX-2 levels were not significantly altered between benign and malignant thyroid nodules (IGF-II) or nodular (FTC, TTN, CTN) and normal thyroid tissues (COX-2). In contrast, eight- to tenfold upregulation of ets-1 was observed in PTC and three- to fourfold upregulation of ets-1 was observed in FTC (and GD) compared with benign thyroid nodules and normal thyroid tissues. In addition, thyroglobulin mRNA expression was markedly downregulated (50- to 100-fold) in FTC, PTC and GD samples compared with benign nodular and normal thyroid tissues. Hence an ets-1/Tg ratio >20 distinguished differentiated thyroid cancer from benign nodular or normal thyroid tissue. We then studied ets1- and Tg mRNA expression levels in fine needle aspiration cytology (FNAC) samples. However, in a consecutive series of 40 FNAC samples only equivocal results were obtained on 38 benign and two malignant (FTC) thyroid tumour samples. CONCLUSIONS: Upregulation of ets-1 and downregulation of Tg mRNA expression occur in differentiated thyroid cancer and may facilitate pre-operative identification of thyroid malignancy depending on further evaluation of these potentially promising markers in a larger series of benign and malignant thyroid tumours and their FNAC samples.

Adenoma↗
PubMed2005

Guidelines on radioiodine therapy for differentiated thyroid carcinoma: impact on clinical practice.

AIM: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing Multicenter Study Differentiated Thyroid Carcinoma (MSDS) were analyzed. PATIENTS, METHODS: Patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pN0/1/x M0/x (UICC, 5th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131I whole-body scintigraphy (WBS) 3-4 months after RIT. RESULTS: Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131I activity for RIT (1-3 vs. 1-4 GBq; +/- 10%), and in 16% and 60% with regard to 131I activity for WBS (100-300 vs. 100-400 MBq; +/- 10%). CONCLUSIONS: The 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes.

Combined Modality Therapy↗