| 1. |
- de Leede, E. M., et al.
(författare)
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Common variables in European pancreatic cancer registries: The introduction of the EURECCA pancreatic cancer project
- 2016
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 42:9, s. 1414-1419
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Tidskriftsartikel (refereegranskat)abstract
- Background: Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCAs newest project is collecting data on pancreatic cancer in several European countries. Methods: National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. Results: Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. Conclusions: A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.
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| 2. |
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| 3. |
- Anlauf, M, et al.
(författare)
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Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions.
- 2007
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 56:5, s. 637-44
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Brabant, G, et al.
(författare)
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E-cadherin: a differentiation marker in thyroid malignancies.
- 1993
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Ingår i: Cancer research. - 0008-5472. ; 53:20, s. 4987-93
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Tidskriftsartikel (refereegranskat)abstract
- Loss of E-cadherin (uvomorulin), a Ca(2+)-dependent cell adhesion molecule required for normal epithelial function, has been attributed a pathogenetic role in tumor invasion. The expression of E-cadherin was studied in normal and neoplastic follicular epithelium of the human thyroid by Northern blot analysis and immunofluorescence on frozen tissue sections. In the normal thyroid (n = 10) and in benign thyroid disorders (n = 21; toxic diffuse goitre; multinodular goitre; follicular adenomas), E-cadherin mRNA levels were equally high and the follicles were generally stained, mainly along the lateral surface of the epithelial cells, by the anti-E-cadherin monoclonal antibody. In anaplastic thyroid carcinomas (n = 6) E-cadherin expression was very low or lacking. In papillary carcinomas (n = 23), E-cadherin mRNA levels varied from nearly normal to highly reduced, which roughly correlated with the overall immunofluorescence intensity. However, the immunostaining also revealed a heterogeneous "all-or-nothing" expression of E-cadherin among adjacent cells in the same tumor. In the follicular carcinomas (n = 9), E-cadherin mRNA levels were in general rather high but the immunostaining varied considerably. A few papillary and follicular tumors lacked immunoreactive E-cadherin in spite of high mRNA levels. In oxyphilic (Hürthle) cell tumors, comprising both adenomas (n = 4) and carcinomas (n = 2), E-cadherin immunoreactivity was reduced and distributed intracellularly rather than at the cell surface. The expression of E-cadherin in relapsing thyroid carcinomas and in tumors with metastatic spreading was, irrespective of the histiotype, low or lacking. Sequential Northern analysis revealed a close correlation between the expression levels of E-cadherin and the thyrotropin receptor. Together, the data suggest that in human thyroid malignancies both gene expression and posttranscriptional control of E-cadherin may be impaired.
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| 5. |
- Brauckhoff, M., et al.
(författare)
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Limitations of intraoperative adrenal remnant volume measurement in patients undergoing subtotal adrenalectomy
- 2008
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 863-872
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies have shown that a minimum of approximately one-third of one normal adrenal gland is required for sufficient adrenocortical stress capacity. Correlation between intraoperative measurement, determination of remnant size by computed tomography (CT), and adrenocortical stress capacity has not been examined so far. Methods: Twenty-two patients with familial pheochromocytoma (n = 13), sporadic pheochromocytoma (n = 3), and adrenocortical tumors (n = 6) who underwent unilateral or bilateral subtotal adrenalectomy (STAE, 28 adrenal remnants) were prospectively studied. Patients were examined in a multi-slice CT to determine residual adrenal tissue and by ACTH test 4 days and 3 months postoperatively. Results: There was a slight significant correlation between intraoperative and CT calculated volumes (r = 0.77, p < 0.001). However, volumes assessed by CT were almost doubled compared with intraoperative determination (p < 0.001). Although recovery of adrenal function could be observed, no significant changes of remnant volumes could be detected within 3 months. In patients with familial pheochromocytoma, there was a significant correlation between residual adrenal volume and stimulated cortisol levels (P < 0.001). A distinct minimum of adrenal volume for intact adrenocortical stress capacity could not be exactly determined, however, in one patient with only 10% residual adrenal tissue intact stress capacity was found. Conclusions: Residual adrenal tissue of approximately 10-15% offers intact stress capacity. However, an exact determination of the size of an adrenal remnant after STAE has limitations. CT gives larger volumes compared with intraoperative determination. For calculation of a volume-function correlation of residual adrenal tissue, in clinical practice, the determination of relative adrenal residual volume is acceptable. © 2008 Société Internationale de Chirurgie.
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| 6. |
- Dammann, R., et al.
(författare)
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Frequent promoter methylation of tumor-related genes in sporadic and men2-associated pheochromocytomas
- 2005
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Ingår i: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 113:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Franz, F, et al.
(författare)
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The Transcriptional Regulation of FOXO Genes in Thyrocytes.
- 2016
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Ingår i: Hormone and Metabolic Research. - Stuttgart : Georg Thieme Verlag. - 0018-5043 .- 1439-4286. ; 48:9, s. 601-6
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Tidskriftsartikel (refereegranskat)abstract
- FOXO transcription factors are key regulators of DNA damage repair, proliferation and apoptosis in thyrocytes. Thyroid malignancies show impaired FOXO function. In this study, we investigated the transcriptional regulation of FOXO isoforms in thyroid epithelial cells. mRNA expression of FOXO isoforms (FOXO1, 3 and 4) was determined in FRTL-5 cells stimulated with different growth factors and H2O2. Furthermore, the impact of PI3K/AKT signalling on FOXO transcription was investigated in PI3K p110α mutant FRTL-5 cells and regulatory dependence of FOXO transcription on FOXO was studied in FRTL-5 cells with hFOXO3 overexpression. Finally, mRNA expression levels of FOXO isoforms were determined in human epithelial thyroid tumours. Growth factor deprivation induced transcription of FOXO1, 3 and 4, whereas insulin stimulation decreased FOXO1 and FOXO4 transcription in FRTL-5 cells. Inhibition of the PI3K/AKT cascade amplified FOXO1 and FOXO4 expression. In contrast, H2O2 and TSH did not influence FOXO transcription in thyrocytes. Overexpression of PI3K p110α inhibited FOXO3 and induced FOXO4 transcription. In human thyroid tumours, FOXO1 and FOXO3 mRNA levels were significantly downregulated in papillary thyroid carcinoma when compared to normal tissues. In contrast, follicular thyroid carcinomas showed significant upregulation of FOXO4 mRNA.In this paper, we demonstrate an influence of PI3K signalling on FOXO transcription in thyrocytes. Moreover, we show that thyroid cancers exhibit alterations in FOXO transcription besides the previously reported alterations in posttranslational FOXO3 regulation. These findings may add to the concept of targeting the PI3K pathway in advanced thyroid cancers.
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| 8. |
- Gimm, O, et al.
(författare)
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[Lymphadenectomy for thyroid and lymph node carcinomas].
- 2007
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Ingår i: Der Chirurg. - : Springer Science and Business Media LLC. - 0009-4722 .- 1433-0385. ; 78:3, s. 182, 184-8, 190
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Tidskriftsartikel (refereegranskat)abstract
- In general, primary surgery of thyroid carcinoma should consist of total thyroidectomy and lymph node dissection of the cervicocentral compartment. Exceptions are cases of papillary microcarcinoma and prophylactic surgery due to multiple type 2A endocrine neoplasia. Lymph node dissection beyond the cervicocentral compartment also should be compartment-oriented. It is generally indicated if lymph node metastases have been proven. Concerning clinically proven medullary thyroid carcinoma, bilateral cervicolateral lymph node dissection is generally indicated, since lymph node metastases may be missed preoperatively but are often found histologically. In patients with parathyroid carcinoma, en bloc ipsilateral cervicocentral lymph node dissection should be performed in addition to parathyroidectomy and hemithyroidectomy. Lymph node dissection should always be performed systematically, since lymph node metastases may be missed both clinically and by imaging techniques.
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| 9. |
- Gimm, O, et al.
(författare)
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[Prophylactic parathyroidectomy for familial parathyroid carcinoma].
- 2006
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Ingår i: Der Chirurg. - : Springer Science and Business Media LLC. - 0009-4722 .- 1433-0385. ; 77:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Machens, A., et al.
(författare)
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Advances in the management of hereditary medullary thyroid cancer
- 2005
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 257:1, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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