| 1. |
- Carling, Tobias, et al.
(author)
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Hyperparathyroidism of multiple endocrine neoplasia type 1 : candidate gene and parathyroid calcium sensing protein expression
- 1995
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In: Surgery. - 0039-6060 .- 1532-7361. ; 118:6, s. 924-931
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Journal article (peer-reviewed)abstract
- BACKGROUND:Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression and function of a putative calcium sensing protein (CAS) in hyperparathyroidism of MEN 1.METHODS:In 31 parathyroid glands from 17 patients with MEN 1, CAS distribution was studied immunohistochemically and parallel sections were explored for PLC beta 3 mRNA expression by in situ hybridization. Enzymatically dispersed parathyroid cells were analyzed for cytoplasmic calcium concentrations [Ca2+]i and parathyroid hormone (PTH) release.RESULTS:All glands exhibited a heterogeneously reduced CAS immunoreactivity, especially meager in nodularly assembled parathyroid cells. Calcium regulated [Ca2+]i and PTH release tended to be more deranged in the glands possessing the lowest immunostaining. Parathyroid PLC beta 3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC beta 3 expression in endocrine pancreatic tumors.CONCLUSIONS:The findings support variable calcium insensitivity of [Ca2+]i and PTH release in hyperparathyroidism of MEN 1, apparently coupled to heterogeneously reduced CAS expression. For clarification of the role of PLC beta 3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.
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| 2. |
- Skogseid, Britt, et al.
(author)
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Adrenal lesions in multiple endocrine neoplasia type 1
- 1995
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In: Surgery. - 0039-6060 .- 1532-7361. ; 118:6, s. 1077-1082
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple endocrine neoplasia (MEN) type 1 is accompanied by adrenal involvement, but characteristics and clinical handling of this lesion have been insufficiently explored. METHODS: Patients with MEN 1 (n = 43) were monitored (mean, 6.3 years) with annual biochemical and radiologic adrenal evaluation. Adrenal specimens were examined by in situ RNA-RNA hybridization for expression of the MEN1 candidate gene phospholipase C beta 3 (PLC beta 3) and immunostaining for insulin-like growth factor-1 receptor. RESULTS: Altogether 17 patients (40%) displayed adrenal enlargement, which was limited to the adrenal cortex and showed signs of progression, marked atypia, and cancer development in three of them. Only the carcinoma exhibited adrenocortical hormone excess. PLC beta 3 was expressed in the hyperplastic and adenomatous proliferation but not the carcinoma. Pancreatic endocrine tumors with insulin-proinsulin excess were overrepresented in the patients with adrenocortical involvement, but significant insulin-like growth factor-1 receptor immunoreactivity was restricted to the carcinoma. CONCLUSIONS: The prevalent adrenocortical lesion associated with MEN 1 requires regular attention because of malignant potential. It was unrelated to loss of constitution heterozygosity for the MEN1 locus (11q13) and PLC beta 3 expression, except for the cortical carcinoma exhibiting allelic losses involving also the Wiedemann-Beckwith gene at 11p15. Mechanisms for mitogenic relationships between the pancreatic and adrenal lesions of MEN 1 demand further clarification.
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| 3. |
- Hellman, Per, et al.
(author)
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Positron emission tomography with 11C-methionine in hyperparathyroidism
- 1994
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In: Surgery. - 0039-6060 .- 1532-7361. ; 116:6, s. 974-981
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Journal article (peer-reviewed)abstract
- BACKGROUND: Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism. METHODS: Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained. RESULTS: Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET. CONCLUSIONS: The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.
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| 4. |
- Hellman, Per, et al.
(author)
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Postoperative recurrence and hypoparathyroidism in hyperparathyroidism of multiple endocrine neoplasia type 1
- 1998
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In: Surgery. - 0039-6060 .- 1532-7361. ; 124:6, s. 993-999
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Journal article (peer-reviewed)abstract
- Background. Operation and reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is controversial regarding surgical strategy, preoperative localization, and biochemical indexes of recurrence. Methods. Fifty patients with MEN 1 with hyperparathyroidism were followed up 2 to 27 years after subtotal (SPX; n = 35) or total parathyroidectomy with forearm autografiing (TPX; n = 15), including 24 who underwent 28 reoperations because of persistent or recurrent hyperparathyroidism. Results. Persistent or recurrent hyperparathyroidism was seen in 66% and 20% of patients after SPX involving extirpation of at least 3 glands and TPX, respectively, and 100% after single-gland excision as a primary procedure. After reoperation, hypercalcemia was reversed in 33% of patients by SPX and 61% by intended TPX procedures. All patients received vitamin D substitution after TPX, but restricted thyroid function allowed withdrawal in all but 10 patients (36%). Intact serum parathyroid hormone levels in nongrafted and grafted arms rose with time, but only exceptional ratios localized graft recurrence. Localization of recurrent hyperparathyroidism was achieved with 11 C-labeled methionine positron emission tomography. Conclusion. MEN 1 hyperparathyroidism has a high risk of recurrence, and operation may include primarily SPX of at least 3 glands or TPX, although the latter includes a higher risk of long-term hypoparathyroidism. Reoperation should involve TPX with recognition of the enhanced recurrence rate in individuals with postoperative hyperparathyroidism.
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| 5. |
- Hellman, Per, et al.
(author)
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Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 1
- 1998
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In: Surgery. - 0039-6060 .- 1532-7361. ; 124:6, s. 993-999
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Journal article (peer-reviewed)abstract
- Background. Operation and reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is controversial regarding surgical strategy, preoperative localization, and biochemical indexes of recurrence. Methods. Fifty patients with MEN 1 with hyperparathyroidism were followed up 2 to 27 years after subtotal (SPX; n = 35) or total parathyroidectomy with forearm autografiing (TPX; n = 15), including 24 who underwent 28 reoperations because of persistent or recurrent hyperparathyroidism. Results. Persistent or recurrent hyperparathyroidism was seen in 66% and 20% of patients after SPX involving extirpation of at least 3 glands and TPX, respectively, and 100% after single-gland excision as a primary procedure. After reoperation, hypercalcemia was reversed in 33% of patients by SPX and 61% by intended TPX procedures. All patients received vitamin D substitution after TPX, but restricted thyroid function allowed withdrawal in all but 10 patients (36%). Intact serum parathyroid hormone levels in nongrafted and grafted arms rose with time, but only exceptional ratios localized graft recurrence. Localization of recurrent hyperparathyroidism was achieved with 11 C-labeled methionine positron emission tomography. Conclusion. MEN 1 hyperparathyroidism has a high risk of recurrence, and operation may include primarily SPX of at least 3 glands or TPX, although the latter includes a higher risk of long-term hypoparathyroidism. Reoperation should involve TPX with recognition of the enhanced recurrence rate in individuals with postoperative hyperparathyroidism.
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| 6. |
- Norlén, Olov, et al.
(author)
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Peritoneal carcinomatosis from small intestinal neuroendocrine tumors : Clinical course and genetic profiling
- 2014
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In: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 156:6, s. 1512-1522
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Journal article (peer-reviewed)abstract
- Background. One-fifth of all patients with small-intestinal neuroendocrine tumors (SI-NETs) present with or develop peritoneal carcinomatosis (PC). Our aim was to determine the prognosis and genetic profiles of tumors in patients with PC compared with tumors in patients without PC. Methods. We included SI-NET patients (cases with PC, n = 73, and controls without PC, n = 468) who underwent operation between 1985 and 2012. The Lyon prognostic index was used to correlate the amount of PC to survival. DNA samples from patients with (n = 8) and without (n = 7) PC were analyzed with a single-nucleotide polymorphism array (HumanOmni2.5 BeadChip, Illumina) to investigate genetic disparities between groups. Results. Patients with PC had poorer survival (median 5.1 years) than controls (11.1 years). An advanced postoperative Lyon prognostic index was a negative prognostic marker for survival by multivariable analysis (P = .042). Patients with and without PC clustered differently based on loss of heterozygosity and copy number variation data from single-nucleotide polymorphism array of the primary tumors (P = .042). Conclusion. SI-NET patients with PC have poor survival, which diminishes with increasing PC load after surgery. Clustering based on copy number variation and loss of heterozygosity data suggests different genotypes in primary tumors comparing patients with and without PC.
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