Radiotherapy for invasive thymoma and thymic carcinoma

PURPOSE: This study reports clinicopathological features and outcome of thymic tumors. Twenty-seven patients with invasive thymoma and 6 patients with thymic carcinoma who had received radiotherapy either primary or postoperatively were analyzed retrospectively. PATIENTS AND METHODS: All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) or biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. RESULTS: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77.4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p = 0.04). Considering local control, radiation dose was a significant prognostic factor (p = 0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5-year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p = 0.007) and DFS (p = 0.0007). CONCLUSION: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival.     

EVALUATION OF A NEW SCREENING ASSAY PROC® GLOBAL FOR IDENTIFICATION OF DEFECTS IN THE PROTEIN C/PROTEIN S ANTICOAGULANT PATHWAY

In the present study a new assay, ProC® Global, globally estimating the activity of the main plasma components of anticoagulant protein C/protein S pathway, was evaluated with respect to test characteristics and its sensitivity in the detection of deficiency states of protein C and protein S and of increased aPCR. In the ProC® Global assay procedure protein C is activated in patient's plasma by an activator reagent (venom from agkistrodon contortrix). The extent of the prolongation of a sample's aPTT, caused by the activation of protein C, is taken as a measure for its anticoagulant capacity. Ninetyeight patients with one of the above mentioned defects were investigated. Decreased plasma protein C activity and increased aPCR were detected with a sensitivity of 1.0, while only 11 of 14 patients with decreased levels of free protein S antigen showed abnormal results in the ProC® Global assay (sensitivity=0.79). The test can be used in heparinized samples up to 1.0 anti Xa U/ml heparin (UFH and LMWH). When samples from patients on oral anticoagulant treatment are prediluted with factor V deficient plasma the test is sensitive for increased aPCR. © 1997 Elsevier Science Ltd     

Analysis of Competing Risk Parameters in Irradiated Prostate Cancer Patients

PURPOSE: Retrospective competing risk analysis of prognostic factors in definitive-irradiated prostate cancer patients. PATIENTS AND METHODS: Data of 652 patients were analyzed according to three age subgroups (< 65, 65 < or = 75, > 75 years; Table 1). Pre-RT PSA values (median 13.4 ng/ml) were available for 340 patients. Adjuvant hormone therapy (n = 261) consisted either of orchiectomy (n = 151) or LHRH agonist with/without antiandrogen therapy or, in the early years, diethylstilbestrol. Neoadjuvant hormone therapy (n = 31) using LHRH agonists was given 6 months before and during radiotherapy. RESULTS: Biochemical failure was observed in 69/340 patients, 5 years after biochemical failure, 64.9% of them also had failed clinically. The cumulative incidence of local failure (LF) and distant metastases (DM) was 9.4% and 37.2%, respectively; LF and DM at the same time were seen in 18.2%. On multivariate analysis (Tables 2 and 3), advanced stage (relative risk [RR] 4.54), pre-RT PSA > 20 ng/ml (RR 2.79) and poorly differentiated tumors (RR 2.96) were significant predictors of biochemical failure. Advanced stage increased the risk of LF (RR 2.18), DM (RR 3.66), and prostate cancer death (PCD; RR 4.30). Hormone therapy decreased the risk of biochemical failure (RR 0.67), DM (RR 0.59), and PCD (RR 0.60) without reaching statistical significance. Median follow-up was 7.6 years. CONCLUSION: Risk of biochemical failure was predicted by pre-RT PSA, stage, and grade; in patients with biochemical failure, the cumulative incidence of death from intercurrent diseases and PCD was 25.0% and 29.2% after 5 years, respectively. The risk of DM and PCD was predicted by stage and grade. Higher age (> 75 years) decreased the relative risk of LF, DM, and PCD significantly.     

Multicentre evaluation of a new point-of-care test for the quantitative determination of D-dimer

Imprecision studies, interference testing and multicentre method comparisons using patient samples were carried out with of a new point-of-care test for D-dimer (CARDIAC D-Dimer). The CV of the within-series and the day-to-day imprecision with blood samples and control materials were between 7% and 13%. Compared with Tina-quant D-Dimer, CARDIAC D-Dimer showed a good correlation and accuracy (n=353; r=0.91; y=1.06x-0.03), compared with STA LIATEST D-Dimer some poorer accuracy (n=304; r=0.91; y=1.12x-0.03). No interference was detected for different hematocrit values (16% to 51%) and in investigations with hemoglobin (up to 0.13 mmol/l), biotin (up to 30 microg/l), bilirubin (up to 340 micromol/l), intralipid (up to 31.1 mmol/l) and rheumatic factor (up to 79 IU/ml). Overdosing or underdosing by 10 microl did not affect the test result. The diagnostic sensitivity of CARDIAC D-Dimer for the detection of acute venous thromboembolic diseases was 100% in our study. With CARDIAC D-Dimer reliable quantitative D-dimer results can be easily obtained. Because of the good analytical and clinical agreement with Tina-quant D-Dimer, it should be suitable for ruling out venous thromboembolic diseases.     

Sunburn cell formation, dendritic cell migration, and immunomodulatory factor production after solar-simulated irradiation of sunscreen-treated human skin explants in vitro

Using human skin explants, we investigated the effects of two different sunscreen preparations containing a chemical UVB filter alone [sun protection factor (SPF) 5.2] or UVA+UVB filter [SPF 6.2] on sunburn cell formation, dendritic cell (DC) migration, CD86- and CD1a-positive cell number, and tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1, IL-10, and IL-12 production in the skin after irradiation with different doses of solar-simulated UV radiation. Sunscreen- or placebo-treated skin explants were irradiated with solar-simulated UV radiation at 0.5, 1, and 2 minimal erythematous dose equivalents (MEDE) (as determined in an in vivo human study) multiplied by the SPF of the placebo or sunscreens. After irradiation, skin explants were floated on RMPI medium for 48 h. Cells that had emigrated and the skin explants were histologically analyzed, and the soluble mediators were measured in the supernatants by ELISA. Exposure to UV radiation led to concentration-dependent increases in sunburn cell formation and TNFalpha production but a concentration-dependent decrease in DC migration and CD86- and CD1a-positive cell number in the epidermis. Both chemical sunscreens protected against those alterations. The immunoprotective capacity of the sunscreens correlated with their SPF but was independent of the sunscreens' UVA protection capacity, suggesting that UVA is not a major factor for immunosuppression under the conditions used in the model. UV irradiation did not significantly affect the vitality of emigrated DC; the expression of HLA, CD80, and lag on emigrated cells; the number of CD1a-positive cells in the dermis; or the production of IL-1, IL-10, and IL-12. We conclude that our model may be useful in determining the immunoprotective capacity of sunscreens.     

Validation of reference data on wisdom tooth mineralization and eruption for forensic age estimation in living persons

Estimation of dental age is an important part of forensic age estimation in living persons. As the quality of the values given in population-specific reference studies has a great impact on the estimation, the aim of this study was to validate reference data for wisdom teeth mineralization and eruption of a German population concerning the diagnosis of the age limit of 18 years in persons with known age. Mineralization and eruption was evaluated in 307 orthopantomograms of Central European subjects aged 17.5–18.5 years. Dental age was estimated using reference data and compared to chronological age. Statistical methods were used to analyze the differences and to propose adjusted reference values. Estimation of dental age relying on mineralization resulted in overestimations of 2 years on average in 76% of the males and 82% of the females. Using eruption, all men and 75% of the women were overestimated by up to 7 years. The differences between estimated and chronological age in both men and women were associated with the mineralization and eruption stage, respectively. The higher the stage, the higher was the risk of overestimation. The mineralization stages up to stage E were associated with underestimations. Using the proposed adjusted reference values resulted in more accurate estimations of dental age. Validation of reference values for dental age estimation showed great overestimations resulting in high error rates with numerous persons being younger than the estimated dental age. Adjustments are proposed which reduce differences between estimated dental age and chronological age.     

Safety of a universal, virus-inactivated and prion-depleted, pharmaceutical-quality plasma: a randomized, double-blind, clinical trial in healthy volunteers

BACKGROUND: Universal plasma is intended to be transfused irrespective of the blood group. We compared the safety and tolerability of a novel, universal blood group–independent plasma with an ABO‐matched plasma. STUDY DESIGN AND METHODS: In this randomized, double‐blind, active‐controlled, crossover, Phase I trial, 30 healthy adult volunteers (blood group A, B, or AB) were randomly assigned to transfusion of 1200 mL of Uniplas LG and 1200 mL of Octaplas LG (both Octapharma AG) or vice versa. In both periods, plasmapheresis (PPh, 600 mL) preceded the infusion. Blood samples were drawn before and after PPh and 15 minutes, 2 hours, 24 hours, and 7 days after end of plasma transfusion, to assess safety and efficacy. The primary safety outcome was change in hemoglobin (Hb) concentration; secondary safety outcomes were direct antiglobulin test (DAT), complement activation, free Hb, haptoglobin, and indirect bilirubin. Efficacy was assessed by evaluation of coagulation variables. RESULTS: Variations of Hb concentration were similar between treatments and within normal range; 90% confidence interval was within predefined limits of equivalence. No subject exhibited a positive DAT. All other secondary variables which could reflect hemolytic transfusion reactions (HTRs) fell within normal range; this suggests that no HTRs occurred. Most adverse events were of mild intensity; two subjects experienced dyspnea, leading to the withdrawal from the study of one subject. CONCLUSION: Universal plasma was equivalent to ABO‐matched plasma with respect to safety and tolerability. Eliminating the risk of ABO incompatibility, this universal plasma represents an advance over blood group–specific plasma.