The value of cortical stimulation applied to the surgery of malignant gliomas in language areas

This study analyzes the utility of peroperative cortical language mapping applied to the surgery of high-grade gliomas situated within or in close vicinity to speech areas. Fifteen consecutive patients harboring high-grade gliomas located in the dominant hemisphere, causing regressive or minor language troubles, underwent awake craniotomy in our institution between June 1998 and April 2000. The technique of cortical stimulation under local anesthesia for language mapping, initially described by Ojemann and colleagues, was applied with some modifications. All patients tolerated awake craniotomy except one, who was intubated after the mapping procedure. Mapping results confirmed a high variability in location of language sites. It was possible to achieve a gross total tumor removal in all cases. Nine patients (60%) exhibited a transient postoperative aggravation. Two patients (13%) presented permanent phasic aggravation. One patient died 16 days after surgery from pulmonary embolism. Five patients died for tumor progression, with a mean survival time of 16.4 months and a median high-quality survival period of 14.2 months. With a mean follow-up of 9.9 months (range, 18–6 months), the 9 survivors are recurrence-free and reveal no significant change in linguistic abilities. This technique is well tolerated and consents to maximize the extent of surgical removal while minimizing the risks of permanent postoperative deficits. This results in an improvement of survival and quality of life. Received: 26 October 2000 / Accepted in revised form: 26 April 2001     

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia. The Groupe d'Etude des greffes de moelle osseuse (GEGMO)

One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation (STBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multi-institutional study clearly need additional clinical data, ideally from a randomized study.     

Culture of putative Langerhans cell bone marrow precursors: characterization of their phenotype

We searched for the presence of human CD1-positive cells in bone marrow populations in order to characterize putative Langerhans cell precursors. Bone marrow progenitors were cultured in 0.8% methylcellulose supplemented with 10% granulocyte-macrophage (GM) colony-stimulating factor(s) GCT and HTB9. We compared the kinetics of these two factors and found that GCT was the more appropriate for our study. After 8 days of culture, colony-forming units of granulocyte-macrophages (CFU-GM) were tested for the presence of CD1-positive cells using the immunofluorescence technique. Positive cells were counted by cytofluorometric analysis: 9.4% CD1a (BL6), 13.4% CD1c (L161), 4.3% CD1b (NuT2), 4.6% CD2 (T11), and 25.5% CD33 (My9). Ultrastructural features and phenotype were then specified by the immunogold labeling technique using electron microscopy. A subpopulation of CD1-positive cells showed the ultrastructural morphology of bone marrow pro-monocyte/monocyte cells. By using well-characterized monoclonal antibodies, it was demonstrated that these cells expressed the following phenotype: CD14+, CD33+, CD4+, HLA-DR+, HLA-DP+, HLA-DQ-, OKT10-, CD2-. These data indicate that these bone marrow promonocyte/monocyte progenitors express a phenotype similar to that of epidermal Langerhans cells but the density of each antigen is much lower than that observed on mature skin dendritic cells.     

Classification of chronic psychoses types I and II and platelet serotonin levels. Apropos of 38 cases

The authors have examined, within a population of 38 patients, all suffering from chronic psychosis, the concentration of serotonin in the blood platelets as a function of a psychopathologic classification. The 38 patients, 17 men and 21 women, with a mean age of 46 years, diagnosed as schizophrenics (INSERM classification) were categorized according to their specific psychosis (types I and II of J. Guyotat) on examination of their clinical reports by two independent clinicians. This categorization returned 20 psychotics of type I, 16 psychotics of type II and 2 psychotics were difficult to classify. Blood samples were taken from both patients and from 47 controls at 10 o'clock in the morning, two hours after breakfast. The concentration of serotonin in the blood platelets was subsequently examined using the technique of liquid chromatography. The results obtained did not show any significant difference between the chronic psychotics and the control group. The average level of platelet serotonin is 5.09 for psychosis of type I and 3.56 for psychosis of type II, but the value of this difference does not indicate a significant statistical difference; however the tight grouping of serotonin levels in the psychotics of type II looked interesting because they were similar to those of the control in being more homogeneous than those of the psychotics of type I.     

Pentosan polysulfate-induced thrombocytopenia and thrombosis

Pentosan polysulfate is a low-molecular-weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous thrombosis during treatment with pentosan polysulfate. The relationship between pentosan polysulfate and thrombocytopenia is supported by platelet aggregation and serotonin release tests. In the light of the literature and our two cases, it appears that pentosan polysulfate alone as standard heparin and low-molecular-weight heparin can induce thrombocytopenia and thrombosis. Platelet counts should therefore be periodically monitored during pentosan polysulfate treatment. In the case of pentosan polysulfate-induced thrombocytopenia, it seems that heparin or low-molecular-weight heparin should not be instituted during the acute phase even it platelet aggregation studies are negative, because of their low sensitivity. After remission of thrombocytopenia, whether or not glycoaminoglycans can be reinstituted, at least temporarily, after antibody had disappeared is still an open question. © 1994 Wiley-Liss, Inc.     

Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80)

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.