Are anti-vitamin K drugs contraindicated with cetuximab during head-and-neck cancer concomitant radiotherapy?

Two cases of severe skin reactions to cetuximab and concomitant radiation therapy are reported in patients treated for locally advanced head-and-neck squamous cell carcinoma and concurrently treated with an antivitamin K drug for cardiovascular diseases. The role of vitamin K in the epidermal growth factor/epidermal growth factor receptor pathway is discussed. A plea for a specific registry is entered.

Epidemiology and clinical characteristics of larynx and hypopharynx carcinoma: a comparative study in the Hainaut and review of the literature.

INTRODUCTION: The epidemiology and clinical picture of laryngeal and hypopharyngeal carcinomas have changed significantly in the past 50 years. The aim of this study was to analyze selected epidemiological and clinical characteristics of laryngeal and hypopharyngeal carcinoma. METHODS: A complete chart review of all patients records was conducted. All the patients who were diagnosed as having laryngeal or hypopharyngeal cancer from January 1, 2004 through December 31, 2009 were included in the study. The demographics of the patient population, the disease profile were analyzed. RESULTS: 138 patients with laryngeal or hypopharyngeal disease were treated. 76 patients presented a laryngeal cancer. Disease characteristics indicated that most cases of supraglottic cancer were in a locally advanced stage (84.4%), whereas most patients with glottis cancer were diagnosed with early stage (63.3%). A hypopharyngeal cancer was diagnosed in 62 cases. A significant increasing trend in hypopharyngeal cancer has been seen in males. The majority of the patients was alcohol consumers and had a histology showing squamous cell carcinoma. There were 33 females and 105 males whose ages ranged at presentation from 47 to 86 years. Of the 138 patients treated, 24 and 47 patients were respectively T3 and T4 and 37 patients were N1, 37 patients N2 and 10 patients N3 (Table I). Most patients had stage IV disease (65/138). Majority of cases presented with local advanced stage. Of the 138 patients treated, 24 and 47 patients were respectively T3 and T4. The highest rate of local advanced stage was observed in patients with pyriform sinus carcinomas (81%); the lowest rate was observed for glottis tumors (41.8%). Regional lymph node metastases were diagnosed in 61% of the analyzed cases. 37 patients were N1, 37 patients N2 and 10 patients N3. The highest rate (82.2%) of regional lymph node metastases were observed in cases of pyriform sinus carcinomas, and the lowest (31.7%) in glottis carcinomas. Most patients had stage IV disease (65/138). 49 patients received radiotherapy; 48 patients were treated by surgery followed by (chemo)radiotherapy. 41 patients were treated initially by concomitant chemoradiotherapy. CONCLUSION: A tendency for increasingly younger patients to develop larynx and hypopharynx carcinomas was observed. Most patients had stage IV disease but no trend for a percentage increase in locally advanced tumors was observed. A significant increasing trend in hypopharyngeal cancer has been seen in males.

[Cerebral sinovenous thrombosis and acquired antithrombin, protein C and S deficiency during chemotherapy in a young man: report of a case]. / Thrombose des sinus veineux endocrâniens et déficit acquis en antithrombine, protéines C et S au cours d'une chimiothérapie: observation clinique chez un jeune patient.

L-asparaginase is commonly used in the chemotherapy regimens for acute lymphoblastic leukaemia. Its use is associated with thrombotic complications in 1 to 14 % of the cases. The pathogenesis of this complication is still unclear. However, the decrease of antithrombin seems to play an important role. We report a case of a 17-year old man with a acute lymphoblastic leukaemia, who developed a cerebral sinovenous thrombosis due to an acquired deficiency of antithrombin and protein C and S following L-asparaginase chemotherapy. We discuss the use of prophylactic supplements of antithrombin and the value of screening of thrombophilia based on the recent medical literature.

Assessment of erythrocyte shape by flow cytometry techniques.

BACKGROUND: Red blood cell (RBC) rheology is altered in different diseases, including acute conditions such as patients in intensive care units (ICU) with sepsis or with an inflammatory reaction due to postoperative states or intracerebral haemorrhage, or chronic conditions such as diabetes mellitus or terminal renal failure. Several techniques are available to assess alterations in RBC rheology, especially deformability, but they are too cumbersome to be used on a large number of cells. OBJECTIVE: To develop a new, rapid flow cytometry technique for easy assessment of RBC shape in patients. METHODS: In flow cytometry, healthy human RBC shape shows a bimodal distribution related to the biconcave form. On this histogram, the second Pearson coefficient of dissymmetry (PCD) representing the asymmetry of this histogram and the spherical index (M2:M1) were calculated, both representing the spherical shape. This technique was used in healthy volunteers (n=17) and in diseases characterised by abnormalities in RBC rheology, including terminal renal failure requiring haemodialysis (n=28), diabetes mellitus (n=18), sepsis (n=19) and acute inflammatory states (postoperative, intracerebral haemorrhage, chronic obstructive pulmonary disease, epilepsy or severe drug intoxication; n=21). Multivariate analysis was performed to determine the factors influencing RBC shape. RESULTS: Measurement of RBC shape was highly reproducible. A good correlation was observed between the PCD and the spherical index, except in the critically ill patients without sepsis. RBCs were more spherical in patients with terminal renal failure (PCD -0.56 (0.14), p<0.05), diabetes mellitus (PCD -0.59 (0.23), p<0.05), sepsis (PCD -0.58 (0.22), p<0.05) or an acute inflammatory state (PCD -0.65 (0.29), p<0.05) than in healthy volunteers (PCD -0.89 (0.12)). The spherical index was also increased in all populations compared with healthy volunteers (terminal renal failure 2.30 (0.20); diabetes mellitus 2.27 (0.38); sepsis 2.28 (0.37); acute inflammatory state 2.35 (0.42) vs healthy volunteers 2.72 (0.47); all p<0.05). Multivariate analysis demonstrated that the underlying pathology (sepsis, acute inflammatory state, diabetes mellitus, terminal renal failure) was the principal cause of these RBC shape abnormalities. CONCLUSION: RBCs are characterised by an increased spherical shape in many disease states. The measure of the second PCD in flow cytometry is a new, easy method to investigate RBC shape in various diseases. This technique could facilitate the investigation of abnormalities of RBC rheology.

Diagnosis and prognosis of overt disseminated intravascular coagulation in a general hospital -- meaning of the ISTH score system, fibrin monomers, and lipoprotein-C-reactive protein complex formation.

The meaning, the utility, and the prognostic significance of the International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation (DIC) score and other parameters of coagulation activation including soluble fibrin monomer complexes (SFMC), antithrombin and protein C consumption, and formation of lipoprotein-C-reactive protein (LP-CRP) complexes (MDA slope 1 and flag A2) were evaluated in 165 inpatients from a general hospital for whom DIC testing was required by the attending physicians. Of these 165 patients, 148 had an underlying disease that clearly justified the laboratory request from our systematic post hoc review of the clinical charts. Of these 148 patients, 28 had a positive overt DIC score, 19 had an A2 flag, and 4 had both. The DIC score was strongly related to several major markers of coagulation activation such as D-dimers, thrombin-antithrombin complexes, and soluble fibrin and was inversely related to antithrombin and protein C levels, which began to fall from DIC score 4 or higher. The formation of LP-CRP complexes was only related to Gram-negative sepsis and these patients had a strong inflammatory reaction. Independent risk factors for death were high creatininemia, positive overt DIC score, and/or presence of SFMC. In patients with positive DIC score, SFMC positivity and low levels of antithrombin and/or protein C were additional risk factors. The ISTH overt DIC score proves useful and adequate as a marker for clinically significant DIC. Illness severity is further defined by SFMC, antithrombin, and protein C levels. LP-CRP complexes are related to sepsis but not to actual overt DIC and lethal prognosis.

Antigens and granularity of blood monocytes in relation to inflammatory markers and lipids in postmenopausal women.

OBJECTIVES: The menopause is associated with an increase of inflammatory markers (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate interleukines production by monocytes. The aim of this work was to study, the relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal women (n=26) without history of cardiovascular disease, was determined, by flow cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression. Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the granularity of both subsets. CD14+dim monocytes were characterized by a low granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood monocytes granularity was positively correlated with serum lipids indicating that monocytes could uptake modified LDL in circulation and not restricted to subendothelial space.

Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation.

The present paradigm of atherogenesis proposes that low density lipoproteins (LDL) are trapped in subendothelial space of the vascular wall where they are oxidized. Myeloperoxidase (MPO) plays a key role in oxidative damage. We propose that LDL oxidation by myeloperoxidase (Mox-LDL) could occur at the surface of the endothelial cells and not restricted to the subendothelial space. The triad constituted by endothelial cells, circulating LDL and MPO in close interaction, constitutes a synergic mechanism for the genesis of Mox-LDL.

Effects of sample temperature on red blood cell shape in septic patients.

Several recent in vitro studies have observed that alterations in red blood cell (RBC) rheology depend on sample temperature. This possibility could limit the in vivo validity of the assessment of RBC shape. We investigated the effects of sample temperature on RBC shape estimated by flow cytometry in septic patients compared with those of volunteers. 0.5 ml of blood was placed at 4 degrees C, room temperature (20 degrees C) or at 37 degrees C. RBCs were analyzed at 30 minutes (T30) by flow cytometry and results compared to baseline measures. With the flow cytometry technique, the RBC shape of healthy volunteers shows a bimodal distribution related to the biconcave form. On this histogram, we calculated the second Pearson coefficient of dissymmetry--PCD--representing the asymmetry of this histogram. At baseline, RBC PCD was increased in septic patients representing a more spherical shape compared to volunteers (-0.73+/-0.18 versus -0.95+/-0.05; p=0.007). For both groups, RBC shape estimated by the flow cytometry technique was not modified by the temperature of the sample. We conclude that estimation of RBC shape by flow cytometry is not influenced by the temperature of the sample. The present study validates the flow cytometry technique to assess RBC shape in vitro.

[Acute portal thrombosis revealing hereditary hemochromatosis: report of a case]. / Thrombose portale aiguë révélant une hémochromatose héréditaire: à propos d'un cas.

The authors report the case of a 49-year old man in whom an inaugural portal vein thrombosis led to the diagnosis of hereditary hemochromatosis. In this case, the increase in ferritinemia and the T2-weighted MRI hepatic segmental hyposignal were considered as consequences of tissular necrosis while they did probe a real iron overload. Genetic testing, revealing C282Y/H63D compound heterozygoty, provided evidence for a diagnosis of hereditary hemochromatosis. Weekly venesections induced a calculated iron depletion of 3.5 g without occurrence of anemia, further supporting the diagnosis. We suggest that hemochromatosis should be considered in the differential diagnosis of idiopathic portal vein thrombosis when signs of abnormal iron accumulation exist.

Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells.

In B-cell malignancies, it is generally held that the monoclonal components (MC) are produced by the malignant clones. Genetic relatedness implies the concordant expression of light-chain (LC) isotypes in the MC and at the surface of the malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias, immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought in 75 of these patients, and had been found in 23 (31%). Biclonal serum components were detected in three cases. LC concordance could not be assessed in three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients, light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias. The origin of LC discordance remains speculative. It could be due to the emergence of subclones with the same primal VDJ gene rearrangement or, alternatively, to the development of new B-cell clones escaping immune surveillance from deregulated T-cells.

A new device for measurement of fibrin clot lysis: application to the euglobulin clot lysis time.

BACKGROUND: Determination of clot lysis times on whole blood, diluted whole blood, plasma or plasma fraction has been used for many years to assess the overall activity of the fibrinolytic system. We designed a completely computerised semi-automatic 8-channel device for measurement and determination of fibrin clot lysis. The lysis time is evaluated by a mathematical analysis of the lysis curve and the results are expressed in minute (range: 5 to 9999). We have used this new device for Euglobulin Clot Lysis Time (ECLT) determination, which is the most common test used in laboratories to estimate plasma fibrinolytic capacity. RESULTS: The correlation between ECLT and manual method is very tight : R = 0,99; p < 10(-6). The efficiency scores of the method are <4% in intra-assay and <7% in inter-assay. It allows to achieve the tests on hyperlipaemic samples. This new device has been easily integrated in laboratory routine and allows to achieve several ECLT every day without disturbance of laboratory workflow. CONCLUSIONS: The routine use of this new device could be useful in various situations such as assessment in atherosclerosis and arteriosclerosis associated diseases, coagulation survey of liver transplantations, cardiovascular surgery or pharmacological research.It has already provided highly promising results in preliminary studies on the relation between fibrinolysis and cardiovascular risk factors.

Adjuvant intraportal chemotherapy for Dukes B2 and C colorectal cancer also receiving systemic treatment: results of a multicenter randomized trial. Groupe Régional d'Etude du Cancer Colo-Rectal (Belgium).

In a randomized trial, the authors evaluated the possible adjuvant activity of intraportal chemotherapy (with 5-fluorouracil 500 mg/m2/day in continuous infusion for 7 days and mitomycin C 10 mg/m2 at day 7) administered after surgery to half of the patients who underwent a full resection for Dukes B2 or C colorectal cancer. The procedure appeared manageable and safe. Two hundred and sixty patients were initially randomized, among whom 173 were finally considered as fully evaluable after having completed six courses of systemic chemotherapy. The reasons for withdrawal were basically tumoral ones and patients or doctors compliance. After a median follow-up of 4.5 years, no difference could be observed in the patients evolution assessed as relapses or deaths rate, or as relapse-free (at 5 years: 68% in the portal treatment group versus 70% in the control group) or overall survival (at 5 years: 76 versus 74%). The frequency of hepatic metastases (21 versus 18%) was also similar in both groups.

Importance of 5-fluorouracil dose-intensity in a double randomised trial on adjuvant portal and systemic chemotherapy for Dukes B2 and C colorectal cancer.

366 patients fully resected from a Dukes B2 or C colorectal cancer were randomised to receive 6 courses of systemic chemotherapy comprising either 5-fluorouracil (5 FU) alone (arm A: 450 mg/m2/day-5/21 days) or combined folinic acid (FOL) and 5 FU (arm B: respectively 200 mg/m2 racemic form or 100 mg/m2-l-form and 370 mg/m2/day-5/21 days). 173 patients had also been initially randomised to receive one course of intraportal chemotherapy just after surgery or no portal treatment. Oral levamisole (150 mg/day; 3 days every other week) was given to all patients for one year. A significantly higher incidence of leuco-granulocytopenia was observed in the arm A (5 FU alone) inducing more frequent dose delays and adaptations as well as levamisole's withdrawal. Then dose-intensities and dose-intensity products were lower in this arm but the dose intensity expressed in mg/m2/week remained higher (631 +/- 107 vs 557 +/- 99; p < 0.001). The median follow-up in the study was 4.5 years. Relapse free (RFS) and overall survivals (OAS) were prolonged in the 5 FU alone group peculiarly in those patients who had not been randomised for portal treatment. Curves diverged progressively with longer follows-up (at 8 years; RFS in arm A: 67-71% vs 59-53% in arm B; OAS in arm A: 72-74% vs 56-46% in arm B). Patients suffering from a colon or a Dukes C cancer benefited the most from the treatment with 5 FU alone. The results are discussed in the light of other recent adjuvant trials. Well dosed 5 FU over a short period of time without folinic acid may be a valuable and inexpensive adjuvant treatment for colorectal cancer. Levamisole may no longer be recommended in this setting.

[Comparison of 2 techniques for measuring lymphocyte proliferation: tritiated methyl-thymidine incorporation and propidium iodide fluorometry]. / Comparaison de deux techniques de mesure de prolifération lymphocytaire: incorporation de thymidine methyl-tritiée et fluorimétrie à l'iodure de propidium.

In vitro lymphocyte mitogenic stimulation by phytohemagglutinin A was determined in 20 subjects, comparing tritiated thymidine incorporation and nuclear propidium iodide fluorescence. Unexpectedly, no correlation could be found between the two measures. The pitfalls of both methods are reviewed and discussed. The inability to validate one test by the other restricts the interpretation of the results obtained with one method and prevents their generalization. Without another gold-standard at the present time, specific and limited method-dependent norms should be defined.