Preoperative localization of water clear cell giant parathyroid adenoma: A case report.

Primary hyperparathyroidism commonly results from a solitary parathyroid adenoma. A water clear cell parathyroid adenoma represents a rare histological variant. This report presents the challenges of preoperative detection of a giant parathyroid adenoma, which was of the water clear cell variant. A case of severe hypercalcemia in a patient without clinical symptoms and equivocal findings on standard imaging modalities, in which the use of [11C]C-Methionine PET/CT facilitated the preoperative detection of a giant parathyroid adenoma. Histopathological examination confirmed the diagnosis of a water clear cell giant parathyroid adenoma following surgical excision. These findings highlight the significance of advanced imaging techniques in the detection and management of a rare form of parathyroid adenoma.

Brown tumor mimicking metastases-the late manifestation of hyperparathyroidism.

Brown tumors are uncommon manifestations of hyperparathyroidism (HPT) that without awareness are easily misdiagnosed as metastases. This short report highlights the importance of clinical context and clear communication between medical specialties when interpreting complex radiologic findings.

The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer.

The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our aim was therefore to determine the prognostic value of the different uPAR forms in blood from SCLC patients. Serum samples from 92 treatment naive SCLC patients were analysed. Intact uPAR, uPAR(I-III), intact and cleaved uPAR, uPAR(I-III) + uPAR(II-III) and the liberated domain I, uPAR(I) were measured using time-resolved fluorescence immunoassays (TR-FIA 1-3). Assessment of association of the uPAR forms to overall survival (OS) was done using Cox regression analysis adjusted for clinical covariates [age, gender, stage, lactate dehydrogenase (LDH), WHO performance status (PS)]. Multivariate survival analysis demonstrated that high levels of uPAR(I) were significantly (p = 0.009) associated with short overall survival (OS). Patients with uPAR(I) levels above the second tertile had a hazard ratio (HR) of 1.9 (95% confidence interval (CI): 1.1-3.3), compared to patients with levels below the first tertile. High serum uPAR(I) levels are associated with short OS in SCLC patient, independent of LDH and PS.

Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer.

BACKGROUND: The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients. PATIENTS AND METHODS: The uPAR forms were measured in samples from 131 metastatic PC patients. These constituted a subset of patients included in a randomized clinical trial of treatment with total androgen blockade (TAB) versus polyestradiol phosphate (PEP). Pre-treatment serum levels of intact uPAR (uPAR(I-III)), intact plus cleaved uPAR (uPAR(I-III) + uPAR(II-III)) and domain I (uPAR(I)) were measured using time-resolved fluorescence immunoassays (TR-FIAs). RESULTS: High serum levels of each of the uPAR forms were significantly associated with short overall survival (OS). The prognostic impact was strongest in the TAB treated patients with all uPAR forms being statistically significant. In multivariate analysis, uPAR(I-III) + uPAR(II-III) was an independent prognostic factor in TAB treated patients (HR = 5.2, 95% confidence interval (CI): 2.5-10.6, P < 0.0001) but not in PEP treated patients (P = 0.40). In the entire study population, OS was similar in the two treatment groups. The survival analysis showed significant interactions between treatment modality and the level of either uPAR(I-III) or uPAR(I-III) + uPAR(II-III). High levels of uPAR(I-III) + uPAR(II-III) were found to be predictive of effect of PEP versus TAB treatment. Patients with uPAR(I-III) + uPAR(II-III) levels above the median had significantly longer OS (median difference 11.3 months), if treated with PEP rather than with TAB (HR = 1.8, 95% CI:1.1-3.1, P = 0.03). CONCLUSION: uPAR forms are significantly associated with OS. High uPAR(I-III) + uPAR(II-III) predicts longer OS in patients treated with PEP compared to TAB. uPAR forms are promising prognostic and predictive markers in PC.

Intact and cleaved uPAR forms: diagnostic and prognostic value in cancer.

The cellular receptor for urokinase, uPAR, localizes its ligand, uPA, and thereby the plasminogen activation, to the cell surface. uPA also cleaves uPAR, liberating the ligand-binding domain I, and thereby inactivates the binding potential of uPAR for both uPA and vitronectin. The uPA-catalyzed cleavage of uPAR is fast on the cell surface, when uPA is bound to a neighboring uPAR molecule. uPAR can be shed from the cell surface. However, the soluble form cannot be cleaved by uPA. Glycolipid-anchored and soluble forms of intact, uPAR(I-III), and cleaved receptor, uPAR(II-III) and uPAR(I), have been identified in tissue and body fluids. It is well-established, that the total amount of all uPAR forms is a strong prognostic marker in different types of cancer. Using immunoassays, measuring the individual uPAR forms, has revealed that the cleaved uPAR forms are even stronger prognostic markers and have diagnostic utility. This review will focus on the mechanism of uPAR cleavage and the functional consequences, as well as the clinical applicability of cleaved uPAR forms.