[Single, immediate postoperative intra-vesical instillation (SI) compared to a single preoperative intra-vesical instillation of mitomycin C in non-muscle invasive bladder cancer (NMIBC). Phase II randomized trial]. / Instillation préopératoire immédiate (IPOI) de mitomycine C comparée à l'instillation postopératoire précoce (IPOP) dans les tumeurs de la vessie. Étude de phase II randomisée.

OBJECTIVE: A single immediate instillation of mitomycin C is recommended after a complete transurethral resection of the bladder (TURB) in low- and intermediate-risk patients with NMIBC. Actually, post-TURB instillation is seldom used due to logistical difficulties and surgical contraindications. Our aim was to compare patients with single pre-TURB intra-vesical instillation and patients with a single, immediate post-TURB intra-vesical instillation of mitomycin C. METHODS: We performed a multicenter randomized trial between February 17, 2014 and November 24, 2016 (registration number 2012-004341-32). Sixty patients with two or less, primary or recurrent papillary bladder tumors and a negative urinary cytology were planned. Cystoscopy was performed at 3, 6 and 12 months after TURB. Our primary endpoint was disease-free interval. Secondary endpoints were recurrence rate at 3 and 12 months, rate of patients in whom instillation could not be performed and tolerance 1 month after TURB using BCI-Fr score. RESULTS: Among 35 eligible participants, 20 were randomly assigned in the pre-TURB instillation group and 15 in the post-TURB instillation group. Follow-up was comparable: 12,3±1,6 months in the SI group and 10,2±4,5 months in the pre-TURB instillation group. In the post-TURB instillation group, 2 patients didn't have any instillation. We did not identify significant differences in disease-free interval. Tolerance at 1 month after TURB was similar in both groups. CONCLUSION: Tolerance and efficacy were not significantly different. As expected, logisitics were easier for the health providers in the pre-TURB group where all patients had their instillation conversely to the post-TURB group. These results suggest that the advantages of a single immediate pre-TURB instillation warrant further evaluation of this strategy in a phase III randomized trial.

[Prognostic value of testosterone during androgene deprivation therapy]. / Valeur pronostique de la testostéronémie lors de l'hormonothérapie intermittente du cancer de la prostate.

INTRODUCTION: The concept of intermittent androgen deprivation therapy (IADT) for prostate cancer (PCa) was introduced in order to improve treatment tolerance with the same carcinological efficiency as continuous androgen deprivation therapy (CADT). Furthermore, studies have shown that PCa prognosis during CADT was correlated to the extent of testosterone collapse. The aim of this study was to assess the link between testosterone levels at the end of the first off-treatment phase and time to occurrence of castrate-resistant prostate cancer. METHODS: We retrospectively analyzed the files of 69 patients having undergone IADT. Intermittence was offered to the patients showing PSA<4ng/mL after at least six months of androgen deprivation therapy (ADT) using a LHRH analog. CRPC was defined according to the AFU oncological guidelines. Patients were sorted into three groups according to their testosterone levels at the end of the first off-treatment phase T<0.5ng/mL, 0.53.4ng/mL. CRPC free-survival, metastasis-free survival and overall survival as well as adverse events frequency were compared between the groups. The impact of initial ADT duration on CRPC occurrence, mean off-treatment phase duration and IADT duration was also studied. RESULTS: Testosterone levels at the end of the first and second off-treatment phases were not linked to time to CRPC occurence (p=0.5), mestastasis occurence (p=0.4) or death (p=0.3). It was associated neither with adverse effects frequency (p=0.2) nor with cancer-related complications (p=0.6). Initial ADT duration was not linked to CRPC occurrence (p=0.6), mean off-treatment phase duration (p=0.5) or mean IADT duration (p=0.6). CONCLUSION: This study did not show any link between testosterone levels at the end of the first off-treatment phase (before reintroducing ADT) and overall survival, metastasis-free survival and CRPC-free survival. Likewise, it was not associated with the frequency of adverse events or cancer-related complications. Initial ADT duration was not linked to CRPC occurrence or IADT chronological parameters.

A sublethal dose of the neonicotinoid insecticide acetamiprid reduces sperm density in a songbird.

Farmland bird species are particularly exposed to pesticides through various pathways. Among pesticides, neonicotinoids insecticides are commonly used in agriculture, but their influence on bird reproductive capacities is poorly understood. In this study, we experimentally tested the effects of the neonicotinoid acetamiprid on House sparrows' sperm quality and oxidative status following ingestion of a low and field-realistic dose of the compound. To do so, 56 males were captured, held and orally dosed seven times over 19 days of experiment with either a saline solution (control) or an acetamiprid-saline solution, and sperm samples were retrieved before and after the experiment. The overall dose given to the birds corresponded to 0.5% of the LD50 for the Zebra finch (5.7 mg/kg BW) spread into 7 separate doses and administered every three days over the entire duration of the study (ca. 0.07% LD50 per oral dose). Sperm mobility and sperm oxidative status were unaffected by the treatment, but sperm density was. Birds that received oral doses of acetamiprid suffered a significant decline in their sperm density compared to control birds. This result was confirmed by a significant decrease in the activity of the antioxidant enzyme SOD in the sperm of acetamiprid-dosed birds. These results provide the first evidence of sublethal toxicity of acetamiprid in a songbird and suggest that passerine birds' fertility may be negatively affected by very small doses of neonicotinoids in the wild.

[Antiphospholipid antibodies in HELLP syndrome: clinical and biological study in 68 women]. / Anticorps antiphospholipides au cours du syndrome HELLP: étude clinique et biologique à partir de 68 patientes.

PURPOSE: Pregnancy complicated by the HELLP syndrome and antiphospholipid syndrome have rarely been reported. We report a study on anticardiolipin antibodies in HELLP syndrome. METHODS: Between March 1996 and September 1999, anticardiolipin antibodies were checked in all women with HELLP syndrome hospitalised in a maternity of the North of France. The women with positive anticardiolipin antibodies were seen month later in a internal medicine department. RESULTS: In the period 68 women with HELLP syndrome were checked for anticardiolipin antibodies. Apl were present in 9 patients (Incidence 42.8/1000 HELLP Year). They persisted after the accident only in 3 patients. Antiphospholipid syndrome was diagnosed in 2 patients, prevalence between the HELLP syndrome for the 42 month period was 0.03. CONCLUSIONS: HELLP syndrome may be a manifestation linked to the antiphospholipid syndrome and may revealed it.

Cerebral amyloid angiopathy (CAA) with presentation as a brain inflammatory pseudo-tumour.

Cerebral amyloid angiopathy (CAA) is frequent but often asymptomatic. It can induce lobar haemorrhage, rapidly progressive dementia or recurrent transient neurological symptoms, other presentations being less frequent. We report 3 patients in their sixties presenting with a space occupying lesion which was the first manifestation of CAA. They were operated with a diagnosis of cerebral tumour. In all three cases, macroscopy was similar, the lesions were superficial in the cerebral cortex and the preoperative diagnoses were glioblastoma, meningioma and cavernoma. Histologically, the lesions consisted of a large inflammatory granuloma with numerous lipophages and siderophages surrounding capillaries with prominent endothelial cells. Vessels in the near cortex and meninges and within the granuloma harboured heavy amyloid deposits immunolabelled by anti-P component, anti-protein beta A4 with a A40 predominance and anti-apolipoprotein E. Adjacent cerebral cortex showed reactive gliosis and rare senile plaques. Amyloidosis is rarely considered among diagnoses of space occupying lesions. In our three cases, CT scan and MRI changes were related to the presence of an inflammatory granuloma around foci of haemorrhage and amyloid laden vessels.

Focal cortical dysplasia with glioproliferative changes causing seizures: report of 3 cases.

In contrast to neoplasia, lesions of focal cerebral dysplasia are thought to be completed developmental processes of abnormal neuronal migration. We present three children with seizures resulting from brain lesions which pathologically demonstrate regions of both clearcut focal cortical dysplasia and also hypercellularity and monomorphism typical of proliferative lesions such as low grade glial tumor. These cases suggest the existence of a distinct subgroup of patients with prominent glioproliferative changes in association with focal cortical dysplasia, challenging the conventional dichotomy between dysplastic and proliferative categories of brain lesions. Recognition of patients with dual pathology may be of practical as well as theoretical importance.

Chemokine receptors in HIV-1 infection of the central nervous system.

Several members of the chemokine receptor are used as coreceptors for HIV-1 infection in the central nervous system (CNS). CCR5 and CCR3 are coreceptors together with CD4 for HIV-1 infection of microglia, the major target for HIV-1 infection in the CNS. Microglia express CXCR4, but their infection by HIV-1 viruses that use only CXCR4 as a coreceptor is relatively inefficient. CXCR4 is also expressed in subpopulations of neurons that are resistant to HIV-1 infection. Additional orphan chemokine receptors that can mediate HIV-1 or SIV entry are expressed in the brain or neurally-derived cell lines, but their role in CNS infection has not been defined. The pattern of chemokine receptor expression in the brain is likely to determine the tropism of HIV-1 for particular CNS target cells and to impact inflammatory and degenerative mechanisms associated with CNS infection.

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS.

The chemokine receptors CCR5 and CXCR4 are co-receptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage-tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV-1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4-positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication.

[Amyloidosis: definition and classification]. / L'amylose, les amyloses: définition et classification.

Amyloidoses are diseases characterized by deposits of altered proteins in the tissues. The amyloid deposit is always extracellular and presents a fibrillary conformation. 85% of the amyloid protein is constituted of a specific protein of each variety of amyloidosis, while the other 15% consists of other proteins and glycoproteins common to all types of amyloidosis. The same amyloid protein can be associated with various clinical forms and, inversely, different proteins can give the same clinical expression. It is therefore preferable to adopt a biochemical classification of amyloidosis. This classification is based on the identification of the various amyloid proteins by immunohistochemical analysis. About fifteen different amyloid proteins have already been identified. Hereditary amyloidoses are the most heterogeneous forms and amyloidoses of the nervous system are still under investigation. Immunohistochemical analysis of the majority of amyloidoses (represented by amyloidosis AA and AL) can now be performed routinely on tissue samples.

[Embryonal carcinoma and anaplastic seminoma of the testis: diagnostic difficulties]. / Carcinome embryonnaire et séminome anaplasique du testicule: difficultés diagnostiques.

In this case report concerning a testicular tumor, the difficulty of discriminating between embryonic carcinoma with granulomatous reaction and anaplastic seminoma is described. According to the literature and the findings of the present case, the value of immunohistochemical investigations is emphasized, especially the use of anti cytokeratin antibody in the diagnosis of embryonic carcinoma. Therapeutic issues stress the importance of such a diagnosis. Furthermore the immunohistochemical identification of embryonic carcinoma in every case should lead to a new classification of the so-called anaplastic seminoma's entity.

Non-Hodgkin malignant lymphomas and peripheral neuropathies--13 cases.

Non-Hodgkin's malignant lymphomas (NHML) are malignant lymphoid proliferations which may be of B or T cell type. Thirteen observations of an association between peripheral neuropathy and B type NHML are reported. None of the cases had evidence of meningeal propagation or neurotoxicity from chemotherapy. The NHML were classified according to the Working Formulation and Kiel classifications. The various mechanisms of peripheral neuropathy in these cases were split into four broad groups. Group I consisted of four cases in which the peripheral nerve lesions were directly linked to a propagation of malignant cells into the peripheral nervous system; this was revealed by autopsy and/or nerve biopsy. Malignant B cell proliferation was demonstrated in three out of four of these cases by immunolabelling of the infiltrates. Group II included three patients whose serum contained a monoclonal immunoglobulin (IgM) with antimyelin activity, and two who had pathological IgM deposits in endoneurial connective tissue. Group III comprised two cases. The immune dysfunction of the NHML was responsible for a Guillain-Barré syndrome in one, and for a chronic inflammatory demyelinating polyneuropathy in the other. Group IV included two patients in whom the mechanism of the peripheral neuropathy, although almost certainly directly related to the NHML, could not be determined beyond doubt. The peripheral neuropathy might have been a result of a paraneoplasic process or, possibly, an undetected lymphomatous invasion of nervous tissue. All these cases of clinically diverse peripheral neuropathy, which either occurred before the discovery of the haemopathy or arose as complications of it, are discussed along with similar observations reported in the literature. Immunolabelling of lymphomatous proliferations and nerves is now of considerable value for classifying and indicating the exact aetiology of the peripheral neuropathy. It can also detect pathogenic consequences of any associated monoclonal dysglobulinemia. In any event, a direct link between the peripheral neuropathy and NHML represents an indication for intensification of specific chemotherapy, which in some of our patients led to significant regression of the peripheral neuropathy. Nonetheless, in some cases, the link between peripheral neuropathy and NHML could not be established with certainty. Long-term follow-up is essential in such cases. The present results show the importance of a case by case study of patients with NHML and peripheral neuropathy.