[18F-FDG PET and bone scintigraphy to search for bone metastasis of lung cancer]. / TEP au FDG-(18F) et scintigraphie du squelette dans la recherche de métastases osseuses du cancer broncho-pulmonaire.

Initial staging of lung cancer is essential to determine the appropriate therapeutic strategy. 18F-FDG PET is currently considered to be the gold standard. 99mTc bisphonate bone scintigraphy has long been indicated to search for bone metastases but it is not know whether this exploration adds further information after an 18F-FDG PET scan. In order to answer this question, two observers unaware of the clinical situation reread PET scans and bone scintigraphies and results compared with other imaging findings. Between February 2001 and March 2004, 39 patients (13F, 26M, 62 +/- 11 yr) underwent 18FFDG PET and bone scintigraphy (mean interval 17 +/- 17 d). When the two explorations agreed for the diagnosis of bone extension, we considered that bone scintigraphy added nothing. When the two explorations were in disagreement, the other imaging examinations, the clinical features and laboratory results during the five-month minimal follow-up were used to establish the reference diagnosis. 18F-FDG PET and bone scintigraphy were in agreement in 29 patients (74%) with positive results in 12 (31%) and negative results in 17 (43%). The two explorations were in disagreement in 10 patients (26%). Among the five disagreement cases with positive bone scintigraphy and no bone anomaly on the 18F-FDG PET, the anomalies were benign and explained by clinical features (3 patients) or were not confirmed by the clinical course and laboratory results (2 patients). Among the 5 cases with a bone anomaly on the 18F FDG PET, no metastasis could be identified during clinical follow-up. Bone scintigraphy does not enable identification of any bone metastases which were not recognized on the PET scan and therefore should not be performed systematically. Using a computed tomography scan with the 18F-FDG PET could further limit the contribution of bone scintigraphy by providing more precision concerning foci identified on the PET scan.

A noninvasive diagnostic strategy including spiral computed tomography in patients with suspected pulmonary embolism.

We conducted a study to evaluate a noninvasive strategy including spiral computed tomography (CT) in patients with suspected pulmonary embolism (PE). We systematically performed spiral CT, ventilation/perfusion lung scanning, and D-dimer (DD) measurement (VIDAS test), and in some cases (with a normal CT with nondiagnostic lung scan and increased DD) performed venous ultrasonography (US) on 247 consecutive patients with clinically suspected PE in our hospital. Patients in whom PE was deemed absent were not given anticoagulants. All patients were followed for 3 mo. The prevalence of PE in the 228 patients who could be evaluated was 42% (96 of 228). PE was confirmed by spiral CT in 73% of the patients, by a high-probability lung scan in 4%, and by findings on US in 23%. PE was ruled out by a normal lung scan in 14% of the patients, by a normal DD concentration (< 500 ng/ml) in 31%, by an obvious differential diagnosis on spiral CT in 18%, by a similar prior lung scan in 11%, and by the combination of normal spiral CT findings, a nondiagnostic lung scan, a DD concentration > 500 ng/ml, and normal US in 26%. Pulmonary angiography was performed in only two patients, both of whom had a normal spiral CT scan and a high-probability lung scan, and was normal. The 3-mo risk of thromboembolism in patients not given anticoagulants, based on the results of the diagnostic protocol, was 1.7% (95% confidence interval: 1.5 to 2.3%). There were no deaths. The noninvasive strategy of combining spiral CT, lung scanning, DD measurement, and in some cases US, in patients with suspected PE yielded a definite diagnosis in 99% of patients, and appeared to be safe.

[Value of plasma D-dimer assays in the diagnosis of venous thromboembolism]. / Intérêt du dosage des D-dimères plasmatiques dans le diagnostic des accidents thrombo-emboliques veineux.

The diagnostic usefulness of measuring plasma D-dimers using the ELISA method and the latex agglutination test has been prospectively evaluated in 117 patients hospitalized for suspicion of acute venous thrombo-embolism (AVTE): pulmonary embolism was suspected in 80 patients and the remaining 37 had a suspicion of deep vein thrombosis of the lower limbs. The diagnosis of AVTE was confirmed in 50% of the patients, all of whom underwent gold standard invasive investigation i.e. pulmonary angiography and/or contrast venography. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimers plasma concentration exceeding 500 ng/ml for the diagnosis of AVTE were respectively 98, 58, 97 and 70% when using the ELISA method, and 86, 71, 84 and 75% when using the latex assay. In 47 patients whose lung scans yielded abnormalities of indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method was very high (94%), but that of latex assay was low (67%). Our results demonstrate that measuring the plasma D-dimers by the latex assay should not be used in the diagnosis of AVTE. On the other hand, the ELISA method might be of great interest in the diagnostic strategy of AVTE, as a normal concentration of D-dimers rules out almost definitely the diagnosis of AVTE, and hence, spares from performing invasive investigations.

Diagnostic and prognostic value of Cyfra 21-1 compared with other tumour markers in patients with non-small cell lung cancer: a prospective study of 116 patients.

The diagnostic value of Cyfra 21-1 in non-small lung cancer (NSCLC) has been established, but few studies have focused on its prognostic value. The aim of this study was to compare that of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 125, neuron-specific enolase and squamous cell carcinoma antigen. 116 patients with unresectable (n = 88) or resectable (n = 28) NSCLC were prospectively monitored from diagnosis, for a median of 14.4 months. All patients underwent tumour-marker determinations before treatment, then every 3 months. Their diagnostic value was studied using ROC (receiver operating characteristic) curves, based on control measure in 23 patients with benign lung diseases. The prognostic analysis was based on overall survival as the main endpoint. The diagnostic value of Cyfra 21-1 was confirmed, with a sensitivity of 54% and a specificity of 96% at a cut-off value of 3.3 ng/ml. At diagnosis, in the 88 non-surgical NSCLC, besides the presence of metastases (P = 0.017), Cyfra 21-1 (P = 0.017) and CA 125 (P = 0.03) were related to outcome. Elevated levels of Cyfra 21-1 at any time during the disease course was selected by multivariate analysis as additional predictors of poor survival.

[Value of the determination of D-dimers in the diagnostic approach of venous thrombo-embolic disorders]. / Intérêt du dosage des D-dimères dans l'approche diagnostique des accidents thrombo-emboliques veineux.

The aim of this study is to evaluate the usefulness of plasma measurements of D-dimer using ELISA method and latex agglutination test in the diagnostic approach of venous thromboembolism. Among 126 patients suspected of pulmonary embolism (80 pat.) or deep venous thrombosis of the legs (46 pat.), the diagnosis of acute venous thromboembolism has been confirmed using gold standard invasive techniques (pulmonary angiography and/or contrast venography) in 49% of them. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimer plasma concentration above 500 ng/ml, on admission day, for the diagnosis of venous thromboembolism are 98%, 66%, 97%, 74% respectively when using the ELISA method, and 87%, 70%, 85%, 74% respectively when using the latex assay. In the 51 patients with a lung scan showing an indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method is very high (94%) but that of the latex assay is low (67%). The repetition of D-dimer measurement on days 2 and 4 following admission has no significant effect on the sensitivity of the ELISA and latex assays. Our results demonstrate that the measurement of plasma D-dimer concentration using latex assay should not be used in the diagnostic approach of venous thromboembolism because the sensitivity of this test is insufficient for ruling out the presence of the disease. On the opposite, a low concentration of plasma D-dimer measured by the ELISA method might be used to rule out acute venous thromboembolism, and avoid invasive radiological techniques, especially in patients with an indeterminate probability lung scan.

D-dimer and CA 125 levels in patients with ovarian cancer during antineoplastic therapy. Prognostic significance for the success of anti-cancer treatment.

In patients with ovarian cancer before they receive chemotherapy, the level of fibrin degradation products (D-dimer), is correlated with the tumor load. In this study, the evolution of D-dimer was compared in patients receiving antineoplastic therapy with the evolution of the disease. The patients could be classified into three groups. In Group 1 (nine patients), both plasma CA 125 (a tumor-associated antigen) and D-dimer remained elevated; the prognosis was always poor. In Group 2 (eight patients), CA 125 and D-dimer decreased simultaneously, complete remission was observed in two patients, and significant residual tumor was observed in the others. In Group 3 (nine patients), despite an important decrease in CA 125, D-dimer remained elevated during therapy. In this group, complete remission was observed in six patients, and three others showed a large decrease in their tumor load. The combination of a decrease in CA 125 levels with a continuous enhanced level of D-dimer during chemotherapy identified a subgroup of patients with a favorable prognosis.

[Prostate-specific antigen. Interpretation of the results in relation to the sampling method]. / Antigène spécifique de la prostate. Interprétation des résultats en fonction de la méthode de dosage.

The authors compare the two prostate specific antigen assay methods most widely used in France. The first method (RIA Baxter) uses an isotope marker (Iodine 125), the other (EIA Biotrol) uses an enzymatic marker (alkaline phosphatase). Prostate specific antigen was assayed by means of these two techniques in two groups of patients: one group of 49 men considered to be free of any prostatic disease, recruited from blood donors; another group of 89 male patients in whom a prostate specific antigen assay was performed prospectively at the first urology outpatients visit. The two prostate specific antigen assay techniques gave different results, but the values obtained by these two methods were not discordant. It is therefore possible to define a coefficient of proportionality of 1.45 regardless of the prostate specific antigen concentration or the urological disease considered (EIA Biotrol x 1.47 = RIA Baxter).

Ultraviolet irradiation of platelet concentrates: feasibility in transfusion practice.

Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.

Fructose is as good a fuel as glucose for exercise in normal subjects.

50 g fructose and 50 g glucose loads, naturally 13C labelled, were orally administered in random order to six healthy subjects submitted to 90 mn exercise at VO2 max/2 on a treadmill. 13CO2/12CO2 variations in the expired air were followed before and after exercise for a total of 240 min. On the whole, fructose appeared to be as good a fuel as glucose during exercise even if slight but significant differences in kinetics were observed: the delta 13C peak values at 90 min were significantly lower with fructose. Between 90 and 240 min, delta 13C remained higher but not significantly with 13C-fructose than with 13C-glucose. During exercise, plasma glucose and insulin levels were significantly lower (p less than 0.05 and p less than 0.01) after fructose than after glucose. We conclude that fructose can be readily used during exercise by healthy subjects.

Comparison of thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator, streptokinase, single-chain urokinase, high molecular weight and low molecular weight urokinase in human plasma in vitro.

Thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator (t-PA) from melanoma cells (mt-PA), recombinant t-PA (rt-PA), streptokinase (SK), single-chain urokinase plasminogen activator (scu-PA), and high and low molecular weight urokinase (HMW UK, LMW UK) were compared in vitro by means of systems using human plasma. Thrombolytic activities were tested on standard or labeled hanging clots. When compared on the basis of urokinase international units, t-PA appeared to be slightly more active than scu-PA and streptokinase, and about 10-fold more active than both preparations of UK when they were diluted in plasma. Fibrinolytic activity was evaluated by measuring the lysis time of recalcified plasma containing variable amounts of thrombolytic agents. t-PA was shown to be twice as active as HMW UK, which was itself more active than LMW UK. When scu-PA and both types of UK were compared on bovine fibrin plates, they showed similar fibrinolytic activity, but the t-PA calibration curve was not parallel to those obtained with UK and scu-PA. Relative thrombolytic and fibrinogenolytic properties were studied for each thrombolytic agent. For similar thrombolytic activities, fibrinogenolysis provoked by scu-PA was less marked than with t-PA and with both UK, while SK showed the highest activity. Our results demonstrate that the thrombolytic/fibrinogenolytic ratio is much more favorable to t-PA and scu-PA than to both forms of UK. Another observation clearly shows that fibrinogenolysis can be induced in vitro in human plasma by high doses of t-PA. This consequence may be important since the therapeutic use of t-PA can be associated with high concentrations of t-PA, and thus t-PA infusion could lead in vivo to severe fibrinogen breakdown. In addition, the methodology described could be useful in standardizing comparison between different species of thrombolytic agents.

Fetal death: coagulation defects and management. Report of 20 cases with study of the half-life of [125I]fibrinogen.

This report concerns 20 patients with intrauterine fetal death. Blood samples for coagulation studies were obtained before, during and after delivery. No clinical defibrination or bleeding was noted. Coagulation defects were observed as follows: 2 biological defibrinations: The first case was a pregnancy of 32 wk with retention for more than 12 wk; hypofibrinogenemia was noted in all 6 samples, between 180 and 280 mg/100 ml. The second was a pregnancy of 32 wk with retention for more than 8 wk; fibrinogenemia was between 170 mg/100 ml and 140 mg/100 ml. 2 intravascular coagulations with normal fibrinogenemia, increase of fibrin degradation products and positive ethanol tests. 3 cases with slight coagulation defects that were difficult to explain. The coagulation defects appeared to be transient, and sometimes resolved themselves spontaneously. Induction of labour was made in 19 cases; quinine sulfate, used in 17 cases, was remarkably successful (1 intolerance, 1 failure). Study of the half-life of [125I]fibrinogen was made in 18 of the 20 cases. On average, it was reduced by half in comparison with the half-life of healthy men. The decrease was noted even in cases of fetal deaths without the coagulation defects detected by classical tests. The half-life of [125I]fibrinogen in 6 pregnant women before therapeutic abortion was also studied. The decrease of half-life was noted. Changes of metabolism of fibrinogen during pregnancy are discussed.