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Biomedical subjects

E Jouanneau

Publications and source records attributed to E Jouanneau.

At least 19 recordsLinked to original sources

[Dendritic cells and gliomas: a hope in immunotherapy?].

Immunotherapy has been explored for several decades to try to improve the prognosis of gliomas, but until recently no therapeutic benefit has been achieved. The discovery of dendritic cells, the most potent professional antigen presenting cells to initiate specific immune response, and the possibility of producing them ex vivo gave rise to new protocols of active immunotherapy. In oncology, promising experimental and clinical therapeutic results were obtained using these dendritic cells loaded with tumor antigen. Patients bearing gliomas have deficit antigen presentation making this approach rational. In several experimental glioma models, independent research teams have showed specific antitumor responses using these dendritic cells. Phase I/II clinical trials have demonstrated the feasibility and the tolerance of this immunotherapeutic approach. In neuro-oncology, the efficiency of such an approach remains to be established, similarly in oncology where positive phase III studies are missing. Nevertheless, dendritic cells comprise a complex network which is only partially understood and capable of generating either immunotolerance or immune response. Numerous parameters remain to be explored before any definitive conclusion about their utility as an anticancer weapon can be drawn. It seems however logical that immunotherapy with dendritic cells could prevent or delay tumor recurrence in patients with minor active disease. A review on glioma and dendritic cells is presented.

Antigen-Presenting Cells↗

[Diffusion and perfusion MR imaging in cerebral lymphomas].

Because of the increasing incidence of cerebral lymphoma, it is critical for patient management to recognize the MR features of this disease. We present the characteristic morphological and functional MRI features of this tumor. The findings on MRI studies, including morphological, diffusion and perfusion imaging, performed in 9 biopsy-proven cases of cerebral lymphoma with 13 lesions are presented and analyzed, and are discussed in comparison with published literature data. All patients underwent diffusion-weighted imaging with a single shot echo-planar pulse sequence. Dynamic susceptibility-contrast MRI was performed using a T2*-weighted gradient-echo echo-planar sequence after intravenous injection of chelates of gadolinium at the rate of 6 ml/s and a temporal resolution of 1 second. All cases of cerebral lymphoma appeared hypointense or isointense on T1-weighted images and in 75% of cases iso- or hypointense on T2-weighted images. All lesions enhanced except one in a patient receiving steroid therapy. On diffusion-weighted images, tumours were hyperintense with normal or decreased ADC values (0.717+/-0.152.10-3 mm2/sec, range: 0.550-1.014) and an ADC ratio tumour/normal white matter of 0.974+/-0.190 (range: 0.768-1.410). On perfusion, the signal intensity-time curve of each tumour showed a characteristic type of curve with a significant increase of the signal intensity above the baseline and a low maximum relative cerebral blood volume ratio (rCVBmax) of 1.43+/-0.64 (0.55-2.62). Due to their higher cellularity, the lack of neoangiogenesis, and the increased permeability of the blood-brain barrier related to the infiltration of blood vessels wall by lymphomatous cells, cerebral lymphoma presents characteristic diffusion and perfusion MRI features that should be useful for diagnosis and patient follow-up.

Adult↗

Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model.

The prognosis of malignant gliomas remains dismal and alternative therapeutic strategies are required. Immunotherapy with dendritic cells (DCs) pulsed with tumour antigens emerges as a promising approach. Many parameters influence the efficacy of DC-based vaccines and need to be optimised in preclinical models. The present study compares different vaccine schedules using DCs loaded with tumour cell lysate (DC-Lysate) for increasing long-term survival in the GL26 orthotopic murine glioma model, focusing on the number of injections and an optimal way to recall antitumour immune response. Double vaccination with DC-Lysate strongly prolonged median survival compared to unvaccinated animals (mean survival 87.5 days vs. 25 days; p < 0.0001). In vitro data showed specific cytotoxic activity against GL26. However, late tumour relapses frequently occurred after 3 months and only 20% of mice were finally cured at 7 months. While one, two or three DC injections gave identical survival, a boost using only tumour lysate after initial DC-Lysate priming dramatically improved long-term survival in vaccinated mice, compared to the double DC-Lysate group, with 67.5% of animals cured at 7 months (p < 0.0001). In vitro data showed better specific CTL response and also the induction of specific anti-GL26 antibodies in the DC-Lysate/Lysate group, which mediated Complement Dependent Cytotoxicity. These experimental data may be of importance for the design of clinical trials that currently use multiple DC injections.

Adoptive Transfer↗

Neurosurgery and the intracranial venous system.

1) Numerous of the so-called "unpredictable" post-operative complications are likely to be related to the lack of prevention or non-recognition of venous problems, especially damages to the dangerous venous structures, namely: the major dural sinuses, the deep cerebral veins and some of the dominant superficial veins like the vein of Labbé. 2) Tumors invading the major dural sinuses (superior sagittal sinus, torcular, transverse sinus)--especially meningiomas--leave the surgeon confronted with a dilemma: leave the fragment invading the sinus and have a higher risk of recurrence, or attempt at total removal with or without venous reconstruction and expose the patient to a potentially greater operative danger. Such situations have been encountered in 106 patients over the last 25 years. For decision-making, meningiomas were classified into six types according to the degree of sinus invasion. Type 1: meningioma attached to outer surface of the sinus wall; Type II: one lateral recess invaded; Type III: one lateral wall invaded; Type IV: one lateral wall and the roof of the sinus both invaded; Types V and VI: sinus totally occluded, one wall being free of tumor in type V. In brief, our surgical policy was the following: Type I: excision of outer layer and coagulation of dural attachment; Type II: removal of intraluminal fragment through the recess, then repair of the dural defect by resuturing recess. Type III: resection of sinus wall and repair with patch (fascia temporalis). Type IV: resection of both invaded walls and reconstruction of the two resected walls with patch. Type V: this type can be recognized from type VI only by direct surgical exploration of the sinus lumen. Opposite wall to the tumor side is free of tumor, it is possible to reconstruct the two resected walls with patch. Type VI: removal of involved portion of sinus and restoration with venous bypass. 3) As 20% of the patients presenting with manifestations of intracranial hypertension due to occlusion of posterior third of the superior sagittal sinus, torcular, predominant lateral sinus or internal jugular vein(s) develop severe intracranial hypertension, venous revascularisation by sino-jugular bypass--implanted proximally to the occlusion and directed to the jugular venous system (external or internal jugular vein)--can be a solution.

Brain Neoplasms↗

Obsessive-compulsive disorder after unilateral caudate nucleus bleeding.

Obsessive compulsive disorders (OCD) may be encountered after basal ganglia lesions of various aetiologies. These lesions are usually bilateral. We report here the case of a 24 years old man who developed a pure compulsive behavior after a unilateral left-sided caudate nucleus hemorrhage due to a cavernoma. The pathophysiology of this compulsive disorder probably reflects a frontal cortex deafferentation mechanism. Behavioral, psychological and medical (serotoninergic) treatments are usually proposed but the efficacy of such therapy remains to be investigated in secondary OCD.

Adult↗

High and low grade oligodendrogliomas (ODG): correlation of amino-acid and glucose uptakes using PET and histological classifications.

Classification and treatment strategy of oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of ODG. We studied 19 patients with proven ODG, comparing standardized uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas-Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas-Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake. In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.

Adult↗

Conformal irradiation for pure and mixed oligodendroglioma: the experience of Centre Leon Berard Lyon.

PURPOSE: To assess whether conformal radiotherapy (CRT) after incomplete surgery or biopsy for pure oligodendrogliomas and mixed gliomas results in decreased long-term sequelae without impairing local control and while reducing irradiated volume. MATERIALS AND METHODS: Twenty-six consecutive patients who presented with pure (21) or mixed (5) oligodendrogliomas and who were given incomplete resections were treated according 3 different strategies: CRT alone (12), chemotherapy followed by CRT (4), and chemotherapy and delayed CRT at the time of tumor progression (10). CRT consisted of multiple noncoplanar fields. Median dose was 60 Gy. Quality of CRT was assessed using tumor and normal tissue conformal indexes. The location of recurrences was assessed with MRI and dosimetric data. Late sequelae were assessed by a questionnaire exploring professional outcome, and also by a Mini Mental State Examination test. RESULTS: The mean overall survival was 5.2 years. Fifteen patients experienced a local relapse. All but 1 occurred in the 95% isodose. Among 11 nonevolutive patients, 6 have a full-time or part-time job. CONCLUSIONS: Despite CRT, infield recurrence was a common feature in patients with oligodendrogliomas and mixed tumors. Further research, including molecular biology typing of tumors and type of treatment, is warranted to improve survival and quality of life.

Adult↗

[Technical aspects and surgical strategy for removal of corticotroph pituitary adenoma].

The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate for each individual case in patients with pituitary-dependent hypercortisolism. Compared with other secreting pituitary tumors, the corticotroph adenoma seems to be the most biologically active tumor. Clinical evidence of hypercortisolism mainly occurs at an early stage of tumor growth when the tumor is very small, below the detection threshold of modern imaging techniques. While the treatment of large tumors remains difficult due to the non-discrete boundary lines of the tumor and extension or invasion, surgical removal of very tiny tumors requires reliable preoperative or peroperative identification in order to achieve total tumor resection for clinical remission and pituitary preservation to prevent hypopituitarism. We reviewed all the current surgical techniques or clever surgical procedures used to achieve both goals with the lowest complication rate. We report here the state-of-the-art of surgical management of corticotroph pituitary adenoma focusing on preoperative radiological and biological data required for performing guided intrasellar surgical exploration and reliable tumor identification. Different technical aspects of the nasosphenoidal approaches are reported as well as the modified transdiaphragmatic or transtubercular transcisternal approaches to tumors in a suprasellar localization or lying along the pituitary stalk. The advantages of minimally invasive surgical techniques such as intrasellar endoscopic surgery are discussed. Adapted surgical techniques for second transnasal surgery indicated for recurrent tumors are described. Guidelines are given for peroperative tumor identification with macroscopic assessment or histological control with frozen section biopsies. Different techniques for tumor removal are discussed from selective microadenomectomy to enlarged pituitary resection and total hypophysectomy. Methods for preoperative guidance of total tumor removal are proposed including histological or biological assessment of normal adjacent pituitary tissue. the strategy of surgical intrasellar exploration and tumor resection is outlined using a set of algorithms. The first is devoted to positive preoperative documentation of the tumor. The second is proposed for the surgical scenario where there is no preoperative MRI evidence of the tumor. Special strategies are discussed for ectopic adenoma or multiple tumors. Revision surgical management after surgical failure or tumor recurrence is described. Special guidelines for surgical treatment of large clinically silent corticotroph macroadenomas are given with emphasis on the high risk of recurrence in comparison with other silent pituitary tumors such as gonadotroph or immunonegative adenomas.

ACTH Syndrome, Ectopic↗

[Corticotroph microadenomas of the pituitary stalk. Diagnostic and therapeutic difficulties].

Thirteen percent of the pituitary adenomas in our series have been corticotroph adenomas. Most have been microadenomas located in the adenohypophysis, more often laterally than posteromedially. In a few rare cases, the corticotroph cells of the pars tuberalis gave rise to an adenoma. Only 16 cases of pituitary stalk adenomas have been published to date. We report here three new cases among a series of 150 patients who underwent surgery for corticotroph adenomas (2% incidence as in the literature). There was no difference in the clinical or biological presentation of intrasellar and pituitary stalk adenomas. This location must be systematically searched on the MRI, but a negative exploration cannot excluded the diagnosis of pituitary stalk adenoma like in intrasellar ones. Two anatomical entities seems to be separated. Some stalk adenomas developed preferentially in the supradiaphragmatic space (one in our series) and are accessible for selective resection. Others develop within the pituitary stalk itself and sometimes in the pars distalis (two patients in our series) which requires section of the pituitary stalk with hypophysectomy if the lower limit is not clearly seen during surgery. The subfrontal or pterional access is the approach of choice for suprasellar tumors. These approaches remain controversial for pituitary stalk adenomas because of the poor visibility of the pituitary stalk and the floor of the third ventricle. The transnasosphenoidal approach with extension to the sphenoidal planum and opening of the optochiasmatic cisterna appears to be the best alternative for surgical removal of these adenomas.

Adenoma↗

Lack of antitumor activity of recombinant endostatin in a human neuroblastoma xenograft model.

Patients with metastatic neuroblastoma are rarely curable with currently available therapy, and the search for new treatment options, which include the use of inhibitors of tumor angiogenesis, is warranted. Here, we have evaluated the efficacy of one of the most promising natural inhibitors of angiogenesis described to date, endostatin, in a human neuroblastoma xenograft model in nude mice. Murine endostatin cDNA was cloned in a bacterial expression vector, expressed as a polyHis-Endostatin fusion protein and purified on Ni2+-NTA beads. The in vitro activity of soluble endostatin was confirmed on bovine capillary endothelial cells and human umbilical vein endothelial cells. The human neuroblastoma cell line SKNAS was injected subcutaneously in the flank of nude mice and administration of the recombinant angiogenesis inhibitor started when tumors reached the size of 100 microm3. Twenty mg/kg of recombinant precipitated endostatin or PBS was subcutaneously injected daily for 12 days. Serum endostatin levels were measured using a competitive enzyme immunoassay. Tumor growth was only slowed down in endostatin-treated mice when compared to control mice, and no statistically significant difference in serum levels of endostatin was observed between endostatin-treated and control groups. The lack of correlation between serum concentration and tumor response raises concern regarding the mechanism of action of endostatin.

Angiogenesis Inhibitors↗

Lack of evidence of osteo-medullary metastases at diagnosis in patients with high grade gliomas.

High grade gliomas usually show a transient response to standard therapy by radiation. A local evolution leads to patient death in most of the cases. Necropsic series suggest that metastatic evolution is rather frequent in lungs, lymph nodes, bones or bone marrow. Are these metastatic deposits present initially? The authors retrospectively reviewed the bone marrow smears performed in 20 patients and the bone scans in 10 patients with high grade gliomas at time of diagnosis. None of these investigations showed metastatic deposits. It is thus suggested that metastatic deposits are probably a late event in the natural history of high grade gliomas. However, if local treatment could reach local control, metastases would probably become a major problem. Thus definitive cure of high grade glioma may require multidisciplinary approach.

Astrocytoma↗

[Should silent corticotroph-cell adenoma be classified as a non-functional pituitary adenoma?].

A 45-year-old man underwent surgery for a silent corticotroph-cell pituitary adenoma which developed in 9 months. The tumor was termed silent because it exhibited increased corticotropic secretion without clinical signs of hypercorticism. This classes it as a non-functional adenoma. The non-functional group includes different types of adenomas such as gonadotroph and other silent thyreotroph and somatotroph adenomas with variable proliferative potential. Silent corticotroph-cell adenoma is considered as an aggressive tumor. In contrast, gonadotroph adenomas usually grow slowly and postoperative tumor remnants can remain stable for years. Because of this variability in tumor growth, the therapeutic decision is difficult if there is a postoperative remnant. No precise guidelines can be established. We suggest that non-functional pituitary adenomas should be considered separately, according to the histological type. This classification is essential for improving knowledge and specifying indications for radiotherapy.

Adenoma↗

[Prolactinoma in man: clinical and histological characteristics].

Prolactinoma usually occurs a small intrasellar tumor in women or as a large tumor in men. To determine whether the predominance of macroprolactinomas in men is due to a delay in diagnosis as has been suggested, or whether there is a sex-related difference in growth rate we conducted a retrospective study in 45 men and 51 women with prolactinomas. Preoperative prolactin level (PRL) was 2,789 573 ng/ml and mean tumor size was 26 2 mm. Prolactin levels and tumor size were significantly higher in women (292 74 ng/ml and 10 1 mm; p<0.01). There was no correlation with age at diagnosis or duration of symptoms. Giant tumors were only observed in men (n=8). Frequency of resistance to bromocriptine (30% vs 5%, p<0.01) and invasive tumors (52% vs 27%, p<0.001) were significantly higher in men than in women. Likewise, proliferation rate was higher for the prolactinomas in men (Ki-67: 2.6 1.1% positive nuclei vs 0.4 0.2%; p=0.08; PCNA: 5.0 2.3% vs 3.7 1.1%). In conclusion, prolactinomas in men are more aggressive than in women. They grow rapidly, often invade the cavernous sinus and are resistant to bromocriptine; proliferation rates can be increased.

Adolescent↗

[Clinical experience with the Sp[hy adjustable valve in the treatment of adult hydrocephalus. A series of 147 cases].

OBJECTIVE: Evaluate the advantages, results and drawbacks of the Sophy adjustable valve (SV) in the treatment of hydrocephalus in the adult. MATERIAL AND METHODS: One-hundred and forty-seven adult hydrocephalic patients (mean age = 64.5 years) shunted with a SV between 1990 and 1997 were retrospectively reviewed. Etiologies of hydrocephalus were: "normal pressure" chronic hydrocephalus (NPH) in 124 and tumoral hydrocephalus with intracranial hypertension in 23 patients. One-hundred fifty shunts were established in 147 patients: 14 ventriculoatrial and 136 ventriculoperitoneal shunts. The initial pressure settings of the SV were: high pressure: 12 times (8%), medium pressure: 136 times (90.6%) and low pressure: 2 times (1.3%). RESULTS: Sixteen patients were lost to follow-up. Two patients died within hours following the procedure. So, the results were analyzed in the 129 remaining patients, with a follow-up of 16.7 months (+/- 17.8). Three patients died from shunted-related causes (2.3%). Eighty-four patients had good results (65%), 25 had fair results (19.5%) and 20 failed to improve or deteriorated (15.5%) after shunting. Fifty-three reoperations were performed in 44 patients (34%), including 37 procedures for mechanical obstruction and 6 for septic complications. Subdural effusions (SDE) occurred in 16 patients (12.5%): 10 surgical evacuations were required in 7 patients; 8 patients were successfully treated using uprating of the SV pressure alone; one was managed conservatively. Fifty-eight pressure readjustments were performed in 47 patients. The pressure settings were uprated 28 times in patients showing clinical or computerized tomographic (CT) features suggesting overdrainage; 20 of those proved to be successful (71.5%). The pressure settings were lowered 30 times in patients showing a lack of improvement after shunting, attributed to underdrainage; only 12 of those proved to be successful (40%). Spontaneous changes of the pressure settings were observed in 14 patients (10.8%). After a MRI exposure, SV pressure changes were observed in 64% of patients. DISCUSSION: The technological refinements that have been proposed to eliminate the overdrainage which occurs in most usual cerebrospinal fluid shunts are reviewed. The SV valve has allowed non-invasive adjustments of its opening pressure in patients showing complications ascribed to inappropriate drainage. The need for additional surgery was eliminated in 20% to 25% of patients of the present series. Because of frequent spontaneous and magnetic resonance-induced pressure changes, the need for repeated controls of valve pressure is to be reemphasized. CONCLUSION: This experience suggests that the SV represents a substantial improvement over standard fixed-pressure valves.

Adult↗

[Cerebral tumors and neoangiogenesis ].

Angiogenesis, which is the development of new vessels arising from the preestablished arborization, plays a fundamental role in tumor growth. Angiogenesis is the combination of antagonistic factors: proangiogenesis and antiangiogenesis factors. On the basis of the concept of relationship between angiogenesis and tumor growth, a promising new way of research is developing with the aim to control angiogenesis with an antitumor goal. The results of the preclinical trials point out the potential of antiangiogenesis agents in the fight against cancer. So, it was showed that tumor growth in animal models of syngenic or human tumors is inhibited by inhibitors of proangiogenic factors (like VEGF or FGF antibody ...) or by antiangiogenic factors. Endostatin, which is a natural inhibitor of angiogenesis, seems to be the most powerful molecule, able to achieve total and final regression of preestablished tumors. However, there are only preliminary data. Clinical trials are on the way. They should bring some answers concerning the place of these antiangiogenesis agents in the traditional therapeutic strategy. In neurooncology, just like in general cancerology, clinical trials have began with different molecules like Marismastat or Thalidomid. A review of the principal actors, preclinical and clinical trials in progress is presented.

Angiogenesis Inhibitors↗

Syringomyelia associated with type I Chiari malformation. A 21-year retrospective study on 75 cases treated by foramen magnum decompression with a special emphasis on the value of tonsils resection.

The purpose of the present study is to evaluate retrospectively the effects of several intra-operative manipulations on the results of foramen magnum decompression (FMD) in patients having syringomyelia associated with type I Chiari malformation. Seventy-five patients having syringomyelia associated with Chiari I malformation were operated on between 1975 and 1996. This population was grouped into 4 subgroups according to the surgical protocol: group I = 42 patients with FMD alone; group II = 16 patients with FMD and third ventricle shunting; group III = 9 patients with FMD and syringosubarachnoid shunting (SSS); group IV = 8 patients with FMD and cerebellar tonsils resection. Pre- and postsurgical magnetic resonance imaging (MRI) studies were analyzed (and compared). Nine patients were lost to follow-up. The results were evaluated in the 66 remaining patients (mean follow-up: 52 months), using the Bidzinski's outcome scale (ref). Two patients (3%) died postoperatively, 31 (47%) had very good results (after additional surgery in 7), 16 (24.2%) had good results (after additional surgery in 7) and 17 (25.7%) had poor results despite further surgery in 9. A total of 27 reoperations were undertaken after primary FMD in 23 patients (35%). Thirty-nine patients (59%) had both pre- and postsurgical MRI evaluation. In 28 (72%) the syrinx had markedly decreased whereas it had remained stable in 11 (28%). Clinical results were not significantly different between the patients of groups I, II and III. Very good or good results were obtained in 24 patients (64.8%) of group I (after additional surgery in 10), in 8 (61.5%) of group II (after additional surgery in 1) and in 7 (87.5%) of group III (after additional surgery in 3). Results in group IV were as follows: 7 patients (87%) had very good results and one had a good result. With a mean follow-up of 28 months, no patient required additional surgery. Postsurgical MRI syrinx reduction was observed in all 8 patients either in the early postoperative course or on delayed followup. It is suggested that tonsils resection might enhance the results of FMD in individuals having Chiari I-related syringomyelia.

Adolescent↗