Prognostic Significance of Preoperative Plasma D-Dimer Level and Clinical Factors in Patients with Spinal Giant Cell Tumor: Retrospective Analysis of 153 Patients in a Single Center.

BACKGROUND: Giant cell tumor (GCT) of the spine is a benign tumor with local aggressiveness and potential for recurrence. No published study has discussed the prognostic role of preoperative D-dimer (D-D) level in spinal GCT. The purpose of this retrospective study was to evaluate the prognostic value of preoperative plasma D-D level and clinical factors. METHODS: Routine clinical parameters and plasma D-D level were analyzed preoperatively. The disease-free survival (DFS) rate was estimated using Kaplan-Meier analysis. Variables with P value <0.1 were subjected to multivariate analysis by Cox regression analysis. P values <0.05 were considered statistically significant. RESULTS: The recurrence rate of spinal GCT was 21.6% in our series. A total of 153 patients were stratified into 2 groups by preoperative D-D level of ≤0.5 µg/mL or >0.5 µg/mL. We found that several clinicopathologic features were associated with the D-D level, including tumor location, the segment involved, Jaffe grade, and recurrence (P < 0.05). Multivariate analysis indicated that the treatment history, resection mode, bisphosphonate treatment, and preoperative D-D level were prognostic factors of DFS (all P < 0.05). In addition, the Jaffe grading system stratified by preoperative plasma D-D level was correlated with DFS of patients with spinal GCT (P < 0.05). CONCLUSIONS: Our study demonstrated that preoperative plasma D-D level, total spondylectomy, bisphosphonate treatment, and treatment history were powerful independent prognostic factors for DFS of patients with spinal GCT, suggesting that preoperative plasma D-D level may be a useful biomarker for predicting recurrence and prognosis of spinal GCT.

Circulating Candidate Biomarkers in Giant Cell Tumors of Bone.

PURPOSE: Approximately 5% of giant cell tumors (GCT) of bone develop pulmonary metastases. Although many biomarkers have been proposed, identification of circulating low abundance molecules may be useful to predict malignant progression. EXPERIMENTAL DESIGN: The hydrogel nanoparticle technique followed by MS was used to detect low molecular weight serum proteins or protein fragments in serum of 20 GCT patients with different clinical course and in ten healthy sera used as control. The most representative low-abundant de novo or differentially abundant proteins were submitted to String database that recognized interconnected activated pathways including protein activation cascade, wound healing, cell-substrate adhesion, and response to stress. Statistics were performed for identification of candidate prognostic factors. RESULTS: Proteome cluster analysis separated metastasis-free from metastatic GCT patients in two well-defined groups where serum levels of signaling transduction mediators and regulators of kinase activity presented a high discriminatory power. Increased expression of proteins STAT5B, GRB2, and OXSR1 was related to a higher probability of metastasis. Multivariate analysis demonstrated that tumor grade and STAT5B were independent prognostic factors. CONCLUSIONS AND CLINICAL RELEVANCE: By using a noninvasive technique, we identified differentially abundant serum candidate biomarkers, also providing prognostic information in patients with GCT of bone.

A high level of colony-stimulating activity in a lung cancer patient with extensive leucocytosis, and the establishment of a CSA producing cell line (KONT).

Colony-stimulating activity (CSA) was demonstrated in materials taken from a patient suffering from lung cancer associated with excessive leucocytosis. CSA was detected not only in his urine, serum and pleural effusion but also in the supernatant of cell cultures originating from the effusion. The excessive leukocytosis of the patient might be due to a CSA producing tumor. A cell line (KONT) originating from the CSA producing tumor has been maintained for 4 years and shown to produce mouse- and human-CSA.

[Hypophosphoremic osteomalacia of connective tissue tumors]. / L'ostéomalacie hypophosphorémique des tumeurs du tissu conjonctif.

The authors undertake a general review of the association between hypophosphoraemia and connective tissue tumour, based upon three personal cases and 27 cases of benign connective tissue tumours, as well as cases of hypophosphoraemia related to malignant tumours or to diffuse dysplasia of connective tissue origin, collected from the literature. This syndrome is distinguished from hypophosphoraemia induced by other tumours (myeloma, carcinoma of the prostate) which are based upon different mechanisms. Hypophosphoraemia, associated with a fall in plasma levels of 1-25 (OH)2 D3 by inhibition of renal 1 alpha hydroxylase, suggests the existence of a complex tubular deficit. Removal of the tumour, most often vascular and intra- or para-osseous, results in rapid normalisation of laboratory then radiological and clinical abnormalities. The physiopathology of the syndrome remains very mysterious. It may be likened to certain tubulotoxic syndromes due to cadmium and in particular to maleic acid. However no precise data yet exists regarding any possible abnormal tumour secretion. In practice, any case of hypophosphoraemic osteomalacia requires investigation to locate a possible tumour of connective tissue, and this all the more so when it is accompanied by very low plasma levels of 1-25(OH)2 D2.

Circulating immune complexes in patients with bone tumours.

Sera from 62 patients with osteogenic sarcoma and 12 with malignant giant-cell tumour were tested for the presence of immune complexes by the 125I-Clq binding assay. Elevated serum Clq binding activity was found in 67.7% of the osteogenic sarcoma patients and in 75% of the giant-cell tumour patients. These results were compared with those obtained with five sera from patients with benign bone tumours and 20 sera from normal young donors. In the last two groups, the incidence of elevated Clq-binding activity was 0% and 5%, respectively. In some patients with giant-cell tumours, pre- and post-operative serum samples were studied, showing a decrease in test values after tumour resection. Preliminary sequential studies of individual patients indicate that the 125I-Clq binding assay may be useful for monitoring patients with bone tumours.

Radioimmunoassay for human calcitonin employing synthetic calcitonin M: its clinical application.

A sensitive and reliable radioimmunoassay for human calcitonin was described and applied to preliminary clinical studies. 125I-labelled synthetic human calcitonin M was purified by gel filtration with Sephadex G-25 and G-100. A nonequilibrium incubation system was applied at the final volume of incubation mixture of 500 mul, in which pooled plasma from normal subjects or hormone free serum was used as carrier protein at 20% incubation mixture. Dextran T 40 coated charcoal, resuspended in 1% bovine serum albumin buffer, was used for the separation of free from bound tracer. This showed the least nonspecific adsorption of tracer to charcoal. The assay was sensitive to 0.1 ng per milliliter of plasma. Recovery of synthetic human calcitonin added to plasma was found to be 101% (S. D., +/- 8). Diluted plasma from a patient with medullary thyroid carcinoma showed a dilution curve parallel to standards. Basal calcitonin levels were less than 0.3 ng/ml in normal subjects. Relatively high values were found in patients with chronic renal failure and in patients with malignant tumors. Extremely elevated values were found in patients with medullary thyroid carcinoma. Provocative calcium infusion tests were also performed.