A large intrathoracic parathyroid adenoma. (17/4752)

A case is described in which an unusually large parathyroid adenoma was visible on the plain chest radiograph taken during the investigation of hypercalcaemia. This was diagnosed preoperatively and a scheme is suggested whereby such a disgnosis can now readily be made. The differential diagnosis is discussed ant the literature is reviewed.  (+info)

Recurrent hyperparathyroidism. (18/4752)

Recurrent hyperparathyroidism occurred in 11 of 295 patients from 10 months to 34 years after an initially successful operation. Seven patients with recurrent hyperparathyroidism had either multiple endocrine adenomatosis type I (MEA) or familial hyperparathyroidism (FHP), one patient had parathyroid cancer, and two patients had renal failure at the time of recurrence. Four of these patients ahd their initial operations elsewhere. Recurrence developed in 33% of patients with MEA or FHP but in only 0.4% of 242 patients without MEA or FHP. The presence of MEA or FHP was known before parathyroid exploration in 18 (86%) of the 21 patients. In patients with MEA or FHP, subtotal parathyroidectomy should be performed if there is more than one gland involved. Other patients should be treated by selective removal of an adenoma because recurrence is rare. Subtotal parathyroidectomy should be reserved for patients with diffuse hyperplasia.  (+info)

Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice. (19/4752)

Expression of cyclooxygenase 2 (COX-2) is believed to play an important role in adenoma formation in murine polyposis models, and inhibition of COX-2 activity may, at least, partly explain the chemopreventative activity of non-steroidal anti-inflammatory drugs against colorectal cancer in humans. However, the mechanism by which COX-2 acts in intestinal tumorigenesis remains unresolved because of conflicting data on the cellular localization of COX-2 in intestinal mucosa. Using immunohistochemistry with specific COX-2 antiserum, we have shown that COX-2 protein is localized to interstitial cells at the base of and within adenomas of the small and large intestine of multiple intestinal neoplasia (Min) mice. No COX-2 staining was observed in dysplastic epithelial cells within adenomas or in histologically normal epithelium. Moreover, COX-2 staining was observed in lamina propria cells of histologically normal intestine of Min mice. No staining was demonstrated in wild-type littermates. The rat monoclonal antibody F4/80 was used to show that COX-2-positive cells represented a subset of the macrophage population present in the intestine of Min mice. Localization of COX-2 to macrophages implies a paracrine effect of COX-2 function on epithelial cells in adenomas and also on histologically normal epithelium. Up-regulation of COX-2 expression in lamina propria macrophages may precede loss of the second functional Apc allele in epithelial cells before adenoma formation in the Min mouse model of intestinal tumorigenesis.  (+info)

Beta-catenin mutations are more frequent in small colorectal adenomas than in larger adenomas and invasive carcinomas. (20/4752)

Loss of serine or threonine phosphorylation sites from exon 3 of beta-catenin has been identified in approximately half of colorectal tumors which lack adenomatous polyposis coli (APC) mutations, but the overall contribution of beta-catenin mutations to sporadic colorectal tumorigenesis is unclear. We therefore used PCR to amplify and sequence exon 3 of beta-catenin from 202 sporadic colorectal tumors. Exon 3 beta-catenin mutations were identified in 6 of 48 small (< 1 cm) adenomas, 2 of 82 large (> or =1 cm) adenomas, and 1 of 72 invasive carcinomas. Eight of the nine mutations, including all of those in the small adenomas and the invasive cancer, involved loss of serine or threonine phosphorylation sites. The percentage of beta-catenin mutations in small adenomas (12.5%) was significantly greater than that in large adenomas (2.4%) and invasive cancers (1.4%; P = 0.05 and P = 0.02, respectively). We conclude that mutation of beta-catenin can be an early, perhaps initiating, event in colorectal tumorigenesis. Small adenomas with beta-catenin mutations do not appear to be as likely to progress to larger adenomas and invasive carcinomas as other adenomas, however, with the result that beta-catenin mutations are only rarely seen in invasive cancers. This suggests that APC and beta-catenin mutations are not functionally equivalent, and that the APC gene may have other tumor suppressor functions besides the degradation of beta-catenin.  (+info)

Expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in parathyroid hyperplasia caused by chronic renal failure versus primary adenoma. (21/4752)

BACKGROUND: In primary hyperparathyroidism, certain genetic abnormalities responsible for parathyroid tumorigenesis are proposed, and it has been reported that the overexpression of PRAD1/cyclin D1 induced by a DNA rearrangement of the parathyroid hormone (PTH) gene is one of the genetic disorders in a number of primary parathyroid adenomas. However, in secondary hyperparathyroidism caused by uremia, the mechanism of monoclonal proliferation in nodular parathyroid hyperplasia is not well understood. To elucidate the mechanism, we examined the expression of PRAD1/cyclin D1, retinoblastoma gene products, and Ki67 in primary adenoma and secondary hyperplasia. METHODS: In adenomas (N = 15) and associated glands (N = 7) with normal histology obtained from patients with primary hyperparathyroidism and in diffuse (N = 14), multinodular (N = 58), and single nodular (N = 28) glands from patients who underwent parathyroidectomy for renal hyperparathyroidism, the expression of these cell cycle regulators was evaluated by immunohistochemical technique. A labeling index was used to define the proportion of cells with positive nuclear staining by each antibody. RESULTS: In 6 out of 15 (40%) primary adenomas, PRAD1/cyclin D1 was overexpressed (a labeling index of more than 500), possibly because of the PTH gene rearrangement, but not in secondary hyperplasia, including single nodular glands. Compared with diffuse hyperplasia, nodular hyperplasia showed a significantly higher expression of PRAD1/cyclin D1 (P < 0.05), retinoblastoma gene products (P < 0.05), and Ki67 (P < 0.05). However, no statistically significant correlation between the expression of PRAD1/cyclin D1 and that of Ki67 was observed in both primary adenoma and secondary hyperplasia. CONCLUSIONS: These results suggest that in secondary hyperplasia caused by uremia, at least remarkable overexpression of PRAD1/cyclin D1 induced by PTH gene rearrangement may be not the major genetic abnormality responsible for tumorigenesis. Heterogenous genetic changes seem to contribute to monoclonal proliferation of parathyroid cells induced by the expression of PRAD1/cyclin D1 or by some other mechanism independent of the amplification of the proto-oncogene.  (+info)

TAP association influences the conformation of nascent MHC class I molecules. (22/4752)

The influence of TAP-MHC class I interactions on peptide binding to the class I heavy chain is assessed during TAP-dependent assembly using Kb-specific Abs that recognize conformational changes induced by assembly with beta2-microglobulin (beta2m) and by peptide binding. A significant portion (45%) of Kb molecules in TAP+, RMA-derived microsomes are associated with the TAP complex as measured by coimmunoisolation of Kb using anti-TAP1 Abs, while only 20% of the Kb heavy chain molecules are isolated as Kbbeta2m complexes with the alpha-Kb-specific Abs, Y-3 or K-10-56. The amount of Kb isolated with Y-3 and K-10-56 increases in proportion to transport and binding of peptide to the Kb molecules within the RMA microsomes. In contrast, less than 5% of the Kb within TAP2-RMA-S microsomes associated with the remaining TAP1 subunit. However, greater than 60% of Kb heavy chain is isolated as K-10-56- and Y-3-reactive Kbbeta2m complexes. We propose that a TAP-MHC class I interaction serves to stabilize the MHC class I:beta2m complex in an immature conformation (Y-3 and K-10-56 nonreactive) prior to high affinity peptide binding, preventing the export of class I molecules complexed with low affinity peptide ligands from the ER.  (+info)

Bilateral hemothorax revealing mediastinal parathyroid adenoma. (23/4752)

We report the case of a 63-year-old woman admitted to hospital because of bilateral hemothorax associated with acute respiratory failure and laterotracheal neoformation. A right thoracoscopy biopsy revealed a paratracheal parathyroid adenoma which was responsible for bilateral hemothorax and primary hyperparathyroidism. A curative resection was successfully performed by cervicotomy.  (+info)

Ultrasound-guided unilateral neck exploration for sporadic primary hyperparathyroidism: is it worthwhile? (24/4752)

The role of preoperative localisation tests before initial neck exploration for primary hyperparathyroidism (PHP) remains controversial, as does the optimal surgical approach. We report our experience with preoperative ultrasound (US) and the operative management of sporadic PHP between 1990 and 1995. Preoperative US was carried out by an experienced radiologist. Three surgeons adopted a policy of 'selective' US-guided unilateral neck exploration (UNE); the fourth surgeon performed routine bilateral neck exploration (BNE). There were 72 patients: 26 men and 46 women, with a mean age of 57.4 +/- 12.5 years (range 21-80 years). All patients underwent initial neck exploration for 'sporadic' PHP, of whom 63 had preoperative US. This was positive in 52 patients; 27 of whom underwent a UNE, 23 had a BNE, and two patients had a UNE converted to a BNE. Patients with 'negative' US (n = 11), and those receiving no preoperative localisation test (n = 90) underwent a BNE. The sensitivity, specificity and accuracy of US were 80% (52/65), 100% (61/61), and 90% (113/126), respectively. Comparable success rates were achieved (BNE: 97% (33/34) vs UNE: 93% (27/29), P < 0.05), with very low morbidity. Failures with the scan-guided UNE were caused by missed contralateral adenomas. An experienced radiologist and a low incidence of multiglandular disease (MGD) are essential prerequisites for the scan-guided unilateral approach. An experienced surgeon, on the other hand, is the only prerequisite for the 'gold standard' bilateral approach.  (+info)