Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

Neurotoxicity and neuroprotection, two aspects of microglial activation in human immunodeficiency virus (HIV) infection

Microglial cells and macrophages are the only cells within the central nervous system, in which productive HIV infection has been unquestionably demonstrated. Those cells play a key role in the origin of the neuronal dysfunction underlying HIV-related cognitive disorders. The neurotoxicity of the cells is both direct, related to HIV proteins, and indirect, through the release by activated macrophages and microglial cells (AMM) of multiple neurotoxic factors. The mechanisms of neuronal damage, the final irreversible stage of which is neuronal apoptosis, are only partly understood but appear to involve oxidative stress and glutamate-receptor mediated toxicity. On the other hand, recent experimental in vitro and in vivo studies, and neuropathological studies in HIV infected patients at different stages of the disease, tend to show that AMM express excitatory amino acid transporters (EAAT) suggesting that in addition to their neurotoxic properties, they also have a neuroprotective role by clearing extra-cellular glutamate and producing antioxidant glutathione. This neuroprotective role could counteract, at least in the early stages of the disease, the neurotoxicity of AMM explaining the discrepancy between the conspicuous microglial activation at that stage and the absence of cognitive disorder, neuronal loss and neuronal apoptosis. It could also explain the regression of the cognitive disorders in some patients who received highly active antiretroviral treatment.     

Imatinib and solid tumours

Imatinib mesylate (Gleevec, Glivec, Novartis, Basel, Switzerland) is a small molecule inhibitor of the tyrosine kinase c-abl, c-kit and the platelet derived growth factor receptor (PDGFR). Imatinib was developed for the treatment of chronic myeloid leukaemia (CML) but was approved both in Europe and the US fro the treatment of CML and gastrointestinal stromal tumors (GIST). Given its activity against both c-kit and PDGFR kinases and its remarkable safety profile, imatinib has been 'tried' in several solid tumors; results however have often been deceiving. We review the current data regarding the activity of imatinib in solid tumors, including GIST.     

Detection of Sp110 by Flow Cytometry and Application to Screening Patients for Veno-occlusive Disease with Immunodeficiency

Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC). This approach will fail to identify VODI patients because the disease is not associated with severe T cell lymphopenia at birth; (2) the SP110 gene contains 17 exons, making it a challenge for Sanger sequencing. The recently developed next-generation sequencing (NGS) platforms that can rapidly determine the sequence of all 17 exons are available in only a few laboratories; (3) there is no standard functional assay to test for the effects of novel mutations in Sp110; and (4) it has been difficult to use flow cytometry to identify patients who lack Sp110 because of the low level of Sp110 protein in peripheral blood lymphocytes. We report here a novel flow cytometric assay that is easily performed in diagnostic laboratories and might thus become a standard assay for the evaluation of patients who may have VODI. In addition, the assay will facilitate investigations directed at understanding the function of Sp110.     

Cancer incidence and survival among adolescents and young adults in France (1978-1997)

Malignancies are rare young French adults but represent the third significant cause of death in the cohort of 15-24 years of age. The aim of this study was to investigate incidence and survival rates of French adolescents and young adults with cancer. All cases of cancer occuring over a 20-year period (1978-1997) in the cohort of patients aged 15 to 24, were obtained from nine population-based registries (10 % of the French population). Basal cell carcinomas of the skin were excluded. 1161 and 1884 cases were recorded in adolescents and young adults, respectively. Overall incidence rates (IR) were 161.4/10(6) in adolescents aged 15-19 years (M/F ratio = 1.3), and 252.6/10(6) in young adults aged 20-24 years (M/F ratio : 1.2). During the 1978-97 period, the IRs appeared stable over the years, +0.4 % [CI95 % = -2.3 ; +3.1] (p = 0.79) for adolescents and +1.7 % [CI95 % = -4.0 ; +7.3] (p = 0.57) for young adults. Five-year overall survival rates were 69.1 % [CI95 % = 66.4-71.8] for adolescents and 74.5 % [CI95 % = 72.3-76.7] for young adults. The 5-year survival rate for patients 15-24 years improved from 62.0 % (CI95 % = 57.5-66.5) in 1978-82 to 80.2 % (IC95 % = 77.7-82.8) in 1993-97. Noteworthy, results in adolescents and young adults are poor compared to the ones from their younger counterparts, especially in patients with acute lymphoblastic leukemia, non-Hodgkin lymphoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and astrocytoma. Further studies are warranted to elucidate whether these differences are due to intrinsic biological properties of the tumor or to differences in clinical practices in the two populations.     

Perte d’objet et menace d’effondrement dans la psychopathologie de l’adolescence

The adolescence corresponds to the period of life where the confrontation in the loss is lively, crucial, particularly at the end of adolescence, when are imperative the changes of identity, ideals, self-image and identity referents, when it is necessary to grant to finish the adolescence without perishing. We present the case of six teenagers having between 17 and 19 years, met for different motives for consultation (teenagers demonstrating delirious episodes or behavioural troubles and misconduct, with social difficulties) having satisfied a protocol of TAT. The end of the adolescence signs the elaboration of the depressive position, the problem of which is reactivated during the presentation of the boards of the TAT. According to the significant registration of the events of life (separation, breaks, delirious episodes), the narrative capacity of certain teenagers will be inhibited. The analysis of narratives in the TAT gives evidence of the modalities of psychic treatment of the loss or quite other traumatizing event. Indeed, the processes of discursive elaboration (formal and thematic) underline the efficiency or the failures of the mechanisms of defence and release, self-regulation and relational modality in front of the representation in the board 3 BM. This picture seems to us to support the reading of the psychic resources concerning the singular treatment modality for loss and for breakdown, strongly present at certain teenagers, whose traumatic load of events of life could not be still exceeded.     

Long-term quality of life after breast cancer: a French registry-based controlled study

Population-based studies on quality of life (QOL) of long-term breast cancer survivors are quite recent and insufficient attention has been paid to the effect of time since diagnosis. We compared long-term QOL of population-based breast cancer survivors 5, 10, and 15 years after diagnosis with that of healthy controls. Breast cancer survivors were randomly selected from three population-based cancer registries (Bas-Rhin, Calvados and Doubs, France) along with healthy controls, stratified for age and place of residence, randomly selected from electoral rolls. Participants completed five self-administered questionnaires: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Short Form-36 (SF-36), Spielberger State-Trait Anxiety Inventory (STAI), Multidimensional Fatigue Inventory (MFI) and a life conditions questionnaire. An analysis of variance was used to compare QOL scores of breast cancer survivors by period (5, 10, or 15 years) of diagnosis with those of controls, adjusted for sociodemographic data and comorbidities. Six hundred and fifty-two cases and 1,188 controls participated in the study. For many QOL scales, scores were significantly different between cancer survivors and controls. A clinically significant difference was evidenced for the fatigue scales, the SF36 physical functioning, role-physical, and role-emotional scales, with more favorable results for controls. Differences decreased with time and 15-year cancer survivors were generally not different from controls. Scores were particularly influenced by age and mean household income. More efforts should be made, specifically during the first 5 to 10 years after diagnosis, to help women with breast cancer to overcome their impairment in QOL.