The threat of misdiagnosis of primary osteosarcoma over the age of 60: a series of seven cases and review of the literature

Background

Osteosarcoma is the most common, non-haematopoietic, primary malignant bone tumour with an incidence of 0.3–0.5 per 100,000. There is some discrepancy in literature concerning the peaks of incidence of osteosarcoma. Some describe only one peak which arises in adolescence, whilst others report a bimodal age distribution with a second peak over the age of 60. In this retrospective study, we evaluated osteosarcoma patients over age 60 treated at our department and reviewed previous studies from the literature.

Patients and methods

Sixty-four patients (40 male, 24 female) with a mean age of 29 years (from 7 to 82) were treated for primary osteosarcomas. At the time of diagnosis, seven patients (two male and five female) were over 60 years of age with a mean follow-up of 46 months after definite diagnosis.

Results

Three out of seven osteosarcomas were primarily radiologically or histologically misdiagnosed, but only one was mistreated with intramedullary nailing at a trauma centre. At last follow-up, two patients had died from the disease, three were alive with disease, and two had no evidence of osteosarcoma.

Conclusions

We did not find an increased incidence of primary osteosarcoma in the elderly; yet, older patients had a higher rate of misdiagnosis due to untypical radiological findings in combination with longer times from the onset of first symptoms to definite diagnosis. In cases of pathological fracture, it is essential to assess whether it is caused by mechanical stress or a primary or secondary tumour before leading into mistreatment, especially in older patients.     

Fibrinolytic dysfunction in insulin-resistant women with previous gestational diabetes

BACKGROUND: Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease. MATERIALS AND METHODS: Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% (n=37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems. RESULTS: Women with p-GDM and IIS had significantly increased body fat mass (BFM) (P相似文献   

Interspecies differences in coagulation profile

Many animals are used in research on blood coagulation and fibrinolysis, but the relevance of animal models to human health is often questioned because of differences between species. The objective was to find an appropriate animal species, which mimics the coagulation profile in humans most adequately. Species differences in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin generation was measured in platelet-poor plasma. Measurements were performed in blood from five different species: humans, rats, pigs, sheep and rabbits. In humans and sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05). Similarly, the endogenous thrombin potential (ETP) was in the same range in humans and sheep. The maximum clot firmness with or without thrombin stimulation was similar in rabbits and humans. The maximum lysis with or without thrombin stimulation was similar in humans and pigs. Significant species differences exist in the coagulation profile with or without thrombin stimulation. Most importantly, sheep had a clotting time most similar to humans and could thus be a suitable species for translational coagulation studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental species to study fibrinolytic pathway and support the usefulness of rabbits as a species for examining platelets.     

Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer

The pathogenesis of hypercoagulability in cancer is not entirely understood. We hypothesized that in cancer patients circulating tissue factor-positive microparticles (TF (+) MPs) are increased and associated with hemostatic system activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex-matched controls, number and cellular origin of TF (+) MPs were determined in plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic system activation. Compared to controls, the median (interquartile range) number of TF (+) MPs was two-fold higher in cancer patients: 25.9 (15.4 - 42.0) x 10 (3) /ml plasma versus 13.1 (11.9 - 19.7) x 10 (3) /ml plasma, p = 0.007. This was mainly due to a higher amount of TF (+) MPs from platelets (13.4 [5.0 - 17.4] x 10 (3) /ml plasma vs. 5.8 [4.5 - 7.5] x 10 (3) /ml plasma, p = 0.017). TF (+) MPs correlated with D-dimer ( ? = 0.48, p = 0.002). High levels of TF (+) MPs in cancer patients and their correlation with D-dimer suggest that TF (+) MPs might be involved in hemostasis activation in cancer patients.     

The fibrinogen -148 C/T polymorphism influences inflammatory response in experimental endotoxemia in vivo

INTRODUCTION: The acute phase reactant fibrinogen plays a critical role in the coagulation system and inflammation. Recently several polymorphisms have been described regulating basal and peak fibrinogen expression. We evaluated the role of a frequent promoter polymorphism in the beta chain of the fibrinogen gene (-148 C/T) in a human in vivo model of experimental endotoxemia. MATERIAL AND METHODS: Healthy volunteers received 2 ng/kg endotoxin (LPS, n=73) as a bolus infusion over 2 min. Blood samples were collected by venipunctures into EDTA anticoagulated vacutainer tubes before LPS infusion. For determination of the fibrinogen promoter polymorphism, we developed a new mutagenic separated polymerase chain reaction assay. RESULTS: Carriers of the -148 T allele had significantly lower TNFalpha expression throughout the whole time course of LPS stimulation and Interleukin-6 levels were trendwise lower, however only basal levels reached statistical significance. No effects were observed on markers of coagulation activation (D-Dimer, Prothrombin F(1+2)). CONCLUSION: Our findings indicate, that the common -148 C/T polymorphism is associated with differences in the TNFalpha release in response to systemic LPS infusion in humans, and add to current evidence that gene-sequence changes in beta-fibrinogen locus can alter the ability of the host to respond to endotoxin.     

Remifentanil, propofol or both for conscious sedation during eye surgery under regional anaesthesia

We performed a prospective, randomized study comparing the efficacy and safety of remifentanil, propofol or both for conscious sedation during eye surgery under retrobulbar blockade. Forty-five unpremedicated patients were assigned to receive remifentanil (group R) (n = 15, mean dosage: 0.05 +/- 0.03 microgram kg-1 min-1), propofol (group P) (n = 15, 1.5 +/- 0.5 mg kg-1 h-1) or a combination (group RP) (n = 15, R: 0.03 +/- 0.01 microgram kg-1 min-1; P: 0.7 +/- 0.2 mg kg-1 h-1). Haemodynamic responses were comparable among all groups. Minimum values for respiratory rate were lower in R patients (R: 7 vs. P and RP: 10 breaths min-1). Perioperative blood gas analysis showed differences in maximum carbon dioxide tensions (R: 51.5 vs. P: 48.3 vs. RP: 45.5 mmHg) and decrease in minimum pH values (R: -0.06 vs. P: -0.0 vs. RP: -0.01). All group P patients reported mild to intense pain during retrobulbar block, while 53% of the group R patients were free from pain. In group RP, 60% of patients experienced no pain and the remaining 40% reported mild pain only. Remifentanil, applied as the sole agent, provided superior pain relief and patient comfort when compared with propofol, but produced greater respiratory depression and postoperative nausea. The combination of remifentanil and propofol provided haemodynamic stability, adequate spontaneous respiration and pain relief, with a low risk of untoward side effects.     

Point of care measurement of lepirudin and heparin anticoagulation during systemic inflammation

BACKGROUND: The number of indications for recombinant human hirudin lepirudin therapy has increased in recent years, and now includes acute coronary syndromes and heparin-induced thrombocytopenia. Hence, point of care monitoring appears desirable for therapy with lepirudin. As CoaguChek Plus (CCP) provides a rapid bedside test to monitor therapy with other anticoagulants, we aimed to determine its suitability for lepirudin therapy. METHODS: Forty-four healthy volunteers received a 2 ng/kg endotoxin infusion (to induce coagulation) together with clinically relevant doses of lepirudin or heparin in a prospective, placebo-controlled, randomised fashion. Measurements of CCP-partial thromboplastin time (aPTT) were compared to laboratory STA-aPTT. RESULTS: As expected, baseline values of CCP-aPTT were shorter than STA-aPTT. Lepirudin increased CCP-aPTT 3-fold, and STA-aPTT 2-fold 1 h after bolus infusion. During lepirudin infusion, the correlation between CCP-aPTT and STA-aPTT was excellent (r=0.86-0.92). Both methods were equally sensitive to over-anticoagulation with heparin. Acute systemic inflammation had little effects on CCP-aPTT. CONCLUSION: CCP-aPTT is suitable for longitudinal point of care monitoring of lepirudin therapy. As baseline values of CCP-aPTT are shorter than STA-aPTT, it is recommended not to indiscriminately change between methods in the follow-up of individual patients.