Patrick François

Centre Hospitalier Universitaire de Tours, Tours, Centre, France

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Publications (49)71.37 Total impact

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    ABSTRACT: A gender difference in the progression of prolactin (PRL) tumors has been disputed for years. To compare tumor characteristics and postoperative clinical course between men and women, and correlate data to estrogen receptor alpha (ERα) expression status. Eighty-nine patients (59 women and 30 men) operated on for a PRL tumor and followed for at least 5 years were selected. Tumors were classified into 5 grades according to their size, invasion and proliferation characteristics. The ERα expression was detected by immunohistochemistry and a score (0-12) calculated as the product of the percentage of positive nuclei and the staining intensity. We found a significant preponderance of high grade tumors among men and a lower surgical cure rate in men (23%) than in women (71%). Patients resistant to medical treatment were mainly men (7/8), 6 of whom showed tumor progression despite postoperative medical treatment which led to multiple therapies and eventually death in 3. The median score for ERα expression was 1 in men (range, 0-8) and 8 in women (range, 0-12) (p<0.0001). The expression of ERα was inversely correlated with tumor size (r = -0.59; p<0.0001) and proliferative activity. All dopamine agonist-resistant tumors and all grade 2b (invasive and proliferative) tumors (from 10 men and 4 women) where characterized by low ERα expression. PRL tumors in men are characterized by lower ERα expression which is related to higher tumor grades, resistance to treatment and an overall worse prognosis.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-0990 · 3.69 Impact Factor
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    ABSTRACT: Background Intramedullary ependymomas are rare and benign tumors in the adult. Little is known about their physiopathology, but the implication of the NF2 gene is suspected because of their presence in a third of patients with type 2 neurofibromatosis (NF2), a disorder caused by mutation of the NF2 gene.Methods We conducted a clinical and genetic study of a family in which 5 of 9 members suffered from intramedullary ependymoma. Karyotyping and CGH array analysis were performed on DNA from peripheral blood lymphocytes from affected participants. The NF2 gene sequences were then determined in DNA from 3 nonaffected and all 5 affected members of the family.ResultsKaryotype and CGH array findings were normal. Sequencing of NF2 revealed a heterozygous deletion, c.811-39_841del69bp, at the intron 8/exon 9 junction, in all affected members that was absent from all nonaffected members. RT-PCR analysis and sequencing revealed a novel NF2 transcript characterized by a skipping of exon 9 (75 bp). This deletion is predicted to result in a 25-amino acid deletion in the N-terminal FERM domain of neurofibromin 2. Modeling of this mutant domain suggests possible disorganization of the subdomain C.Conclusion We report the first family with an NF2 mutation associated with intramedullary ependymomas without other features of NF2 syndrome. This mutation, which has not been described previously, may particularly affect the function of neurofibromin 2 in ependymocytes leading to the development of intramedullary WHO grade II ependymomas. We propose that sporadic intramedullary ependymomas should also be analyzed for this region of NF2 gene.
    Neuro-Oncology 12/2013; 16(2). DOI:10.1093/neuonc/not165 · 5.29 Impact Factor
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    ABSTRACT: Medical treatment of endocrine pituitary tumors with somatostatin analogs depends on tumor type and somatostatin receptor (SSTR) expression. Immunohistochemical detection of these receptors using polyclonal antibodies has given conflicting results. We studied the expression of SSTR2A and SSTR5 with new procedures in 108 pituitary tumors. Using 2 new, specific monoclonal antibodies (clone UMB-1 and UMB-4), 2 fixatives (Bouin-Hollande and zinc-formalin) and 2 technical procedures (manual and automated), SSTR2A and SSTR5 expression was studied in 60 GH (growth hormone), 15 ACTH (adrenocorticotropic hormone), 23 FSH/LH (follicle-stimulating hormone/luteinizing hormone), 7 PRL (prolactin), and 3 TSH (thyroid-stimulating hormone) tumors. Only membrane staining was taken into account, and the SSTR expression was considered positive when more than 5% of the cells were immunoreactive. GH tumors were classified as GH or GH/PRL, densely or sparsely granulated, and into 3 groups according to the percentage of SSTR-immunoreactive cells (group 1: <25%; group 2: 25%-75%; group 3: >75%). Almost all GH tumors expressed SSTR2A (93%) and SSTR5 (83%) at high levels (group 3: >75%) in 52% and 37%, respectively. SSTR2A expression was significantly higher in densely than in sparsely granulated tumors. Moreover, SSTR2A was also expressed in the 3 TSH tumors and weakly expressed in 26% of the FSH/LH tumors, although not in ACTH or PRL tumors. SSTR5 expression was noted in 2 of the 3 TSH tumors, in only 20% of ACTH tumors, and was absent from FSH/LH and PRL tumors. The immunohistochemical detection of SSTR is a reproducible and specific method that could help direct the choice of postoperative medical treatment.
    Human pathology 10/2013; 45(1). DOI:10.1016/j.humpath.2013.08.007 · 2.81 Impact Factor
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    ABSTRACT: We report the case of a 41-year-old woman who underwent cervical total disc replacement at C4C5 and C5C6 levels and fusion at C6C7 level through an anterior right-side approach. After anesthesia recovery, the patient presented left hemiparesia and facial palsy due to large right hemispheric stroke. Diffusion-weighted magnetic resonance imaging was performed as soon as the patient developed neurologic symptoms of stroke and revealed a right internal carotid artery dissection. Digital substraction angiography, endovascular stenting, angioplasty and thrombectomy were performed. Six months after treatment, clinical examination showed mild left-arm spasticity. To the best of our knowledge, only two cases of internal carotid artery stroke without dissection or thrombosis are reported. In conclusion, although vascular complications are rare after anterior cervical spine procedure, internal carotid artery dissection can occur. Suspected risk factors are prolonged retraction of the carotid artery and neck extension.
    European Journal of Orthopaedic Surgery & Traumatology 06/2013; DOI:10.1007/s00590-013-1228-8 · 0.18 Impact Factor
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    ABSTRACT: Objective Central neurocytoma (CN) is a rare intraventricular tumour. Surgery has been highly recommended for CN, although it entails a significant chance to harm the patient. We aimed to provide new data that would support surgical decision-making and optimise patient information about outcomes after surgery. Method Under the auspices of the French Society of Neurosurgery, we conducted a multi-institutional database search in 23 academic hospitals. In all, we reviewed the relevant clinical and radiological data of 82 patients who were operated on for CN between 1984 and 2008, and had their diagnosis confirmed by central pathological review. Results The median follow-up was 61 months (range, 6–96 months). Gross total resection (GTR) was achieved in 48 % of the patients, and subtotal resection (STR) in 52 %. The 5-year overall survival rate was 93.8 % (95 % CI, 93.7–93.9). The 5-year progression-free survival rate was 92.1 % (95 % CI, 91.90–92.2) in patients who underwent GTR, compared with 55.3 % (95 % CI, 55.1–55.5) in patients who had STR (p = 0.01). The overall perioperative complication rate was 66 %. The main causes of postoperative disability were some degree of postoperative paresis and/or aphasia (39 %), memory difficulties (29 %) and temporary hydrocephalus (26 %). GTR was not associated with an increased rate of postoperative complications compared with STR. At last follow-up, Karnofsky Performance Score was at least equal to 80 for 90.6 % of the tested patients. Conclusion Our series emphasised that maximal surgical resection of CNs offers favourable benefit-risk ratio. These data are of importance to properly counsel patients regarding expected outcomes, and to plan relevant preoperative and postoperative investigations like language and memory function evaluation.
    Acta Neurochirurgica 05/2013; 155(7). DOI:10.1007/s00701-013-1732-y · 1.79 Impact Factor
  • F Sauvaget · P François · M Ben Ismail · C Thomas · S Velut
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    ABSTRACT: Intracranial schwannomas not associated with cranial nerves account for less than 1% of surgically treated schwannomas of the central and peripheral nervous system. With only 45 cases reported to date, subfrontal schwannomas are very rare tumors, leaving the issue of their origin controversial. A 66-year-old woman presented with a 1-year history of progressive headaches. Clinical examination revealed hypoesthesia of the nasal tip. CT-scan and MRI studies revealed a large subfrontal tumor thought preoperatively to be a meningioma. Intraoperatively, a large extra-axial tumor arising from the floor of the right frontal fossa was encountered. Histopathology identified the tumor as a schwannoma. This current case gives strong clinical presumption of an origin from the anterior ethmoidal nerve. We reviewed the literature in order to establish the epidemiology of these tumors, from which there appear to be divergent profiles depending on tumor origin and histology. Despite close similarities with olfactory groove meningiomas, patient history and radiological findings provide substantial evidence for differential diagnosis.
    Neurochirurgie 04/2013; 59(2). DOI:10.1016/j.neuchi.2013.02.003 · 0.47 Impact Factor
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    ABSTRACT: Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.
    Acta Neuropathologica 02/2013; 126(1). DOI:10.1007/s00401-013-1084-y · 10.76 Impact Factor
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    ABSTRACT: According to the World Health Organization classification of pituitary tumors, only tumors with systemic metastasis must be considered as carcinomas. Invasive tumors with multiple recurrences are only classified as aggressive tumors or "atypical adenomas". To illustrate the problems encountered in the pathological diagnosis of pituitary carcinoma and in patient management, we present two male patients operated on for an aggressive prolactin pituitary adenoma with and without metastasis. In case 1, 5 surgeries, 3 irradiations, increased doses of dopamine agonists, and trials of temozolomide and carboplatine-VP16 failed to control tumor progression and the appearance of metastases which lead to death 16 years after onset. In case 2, based on the initial diagnosis of an aggressive-invasive adenoma that was resistant to dopamine agonists, gamma-Knife irradiation was initially performed on the intra-cavernous remnant. Eight years after onset, the remnant remained stabilized and the plasma PRL normalized under dopamine agonist. From these 2 cases alongside other cases found in the literature, we propose that the association of certain clinical signs (male sex, dopamine-resistant hyperprolactinemia), radiological signs (invasive macro or giant tumor on MRI) and histological signs (angiogenesis, Ki-67 > 3 %, p53 positive, mitoses >2 per high power field, vascular invasion, up-regulation of genes related to invasion and proliferation, and allelic loss of chromosome 11) might suggest aggressiveness and be suspicious of malignancy before the appearance of metastasis. The early detection of an aggressive phenotype of a prolactin pituitary tumor should permit the earlier establishment of the optimum therapeutic strategy associating surgery and radiotherapy to delay or inhibit metastasis.
    Pituitary 11/2012; 16(4). DOI:10.1007/s11102-012-0448-y · 2.22 Impact Factor
  • A Aubin · S Moriniere · P François · D Bakhos
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    ABSTRACT: Foreign bodies in the transnasal ethmoido-sphenoidal sinus are uncommon. We present a case of unilateral rhinorrhoea caused by a foreign body which had been lodged in the ethmoido-sphenoidal sinus for 38 years. A 40-year-old woman presented with unilateral rhinorrhoea. Computed tomography showed a foreign body located in the right ethmoido-sphenoidal sinus, with a defect of the lamina papyracea and the ethmoid roof. The endonasal approach did not permit extraction of the foreign body. A combined approach allowed the extraction of a pen cap, and the defect of the ethmoid roof was rebuilt. Despite its limitations, the endonasal approach remains the treatment of first choice for osteo-meningeal defects, because of its minimal invasiveness and high success rate. However, in the presented case a combined approach was needed.
    The Journal of Laryngology & Otology 07/2012; 126(9):939-41. DOI:10.1017/S0022215112001284 · 0.70 Impact Factor
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    ABSTRACT: Von Hippel-Lindau disease is an autosomal dominant disorder involving the development of specific tumours in multiple organs, both benign and malignant. In the CNS, the syndrome is characterized by haemangioblastomas of the retina, spinal cord and brain. We report the case of a 15-year-old boy with the diagnosis of aggressive GH-PRL pituitary macroadenoma and a family history of VHL disease. Pituitary resection was performed, although complete excision of the lesion could not be confirmed by the neurosurgeon. A control MRI was done 6 months after surgery and the pituitary lesion was similar to the presurgical image. A second operation allowed partial resection of the tumour followed by targeted radiotherapy. Pituitary adenomas are rare benign tumours in children with macroadenomas observed mainly in boys. These tumours in adolescents often occur in a familial setting or in the context of known genetic defects. Angiogenesis is an important feature of pituitary adenomas and a possible inhibitory role of pVHL in pituitary angiogenesis has been suggested. This GH-PRL pituitary macroadenoma with a VHL mutation might be of particular aggressiveness. Pituitary adenomas are not classically described in VHL syndrome and the medical community should be alerted to its rare occurrence in this location.
    Annales d Endocrinologie 02/2012; 73(1):37-42. DOI:10.1016/j.ando.2011.12.001 · 0.66 Impact Factor
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    ABSTRACT: Central neurocytoma (CN) is a rare intraventricular tumor presenting a benign histologic appearance and favorable prognosis after surgery. In contrast, "atypical" CN is defined by a high MIB1 proliferation index and/or histologic features of malignancy, which are associated with a poorer outcome. This variant of CN remains somewhat controversial. To better characterize CN and its "atypical" variant, a retrospective multicenter study was conducted on 71 patients presenting with CN. A statistical analysis of clinical, radiologic, and histologic data was conducted to validate prognostic factors. The immunohistochemical phenotype of CNs, analyzed by tissue microarrays, and the MIB1 index were evaluated for 45 cases. Tissue microarrays validated the expression of neuronal markers synaptophysin and NeuN, but not that of glial markers glial fibrillary acidic protein and oligodendrocyte transcription factor 2. In the univariate analysis, a tumor volume ≥30 cm (P=0.025), incomplete surgery (P=0.033), and a mitotic count ≥3 per 10 high-power fields (P=0.009) were predictors of a higher risk of recurrence, unlike the other usual histologic features of malignancy and the high MIB1 index. Partial surgery was the only criterion associated with a poorer outcome in the multivariate model. Our results, based on a large multicenter series, show the striking homogeneity of CNs and do not support the use of histologic criteria as reliable markers to define an "atypical" group of CNs. Our study suggests that the extent of surgery is the main factor to be considered in the prognostic assessment of patients with CN.
    The American journal of surgical pathology 02/2012; 36(2):220-7. DOI:10.1097/PAS.0b013e31823b8232 · 4.59 Impact Factor
  • I Zemmoura · S Velut · P François
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    ABSTRACT: The choroidal fissure (CF) is an important landmark that allows approaches to the deepest aspects of the brain. It is the C-shaped site of attachment of the choroid plexus in the lateral ventricles, which runs between fornix and thalamus. The thinness and the absence of neural tissue between the ependyma and pia matter of this part of the medial wall of the lateral ventricles provides a surgical pathway to the third ventricle and perimesencephalic cisterns. A precise knowledge of the microsurgical anatomy of the region, particularly vascular relationships, is essential to consider surgery through the CF. We decided to present the anatomy of the CF in three distinct chapters, corresponding to three compartments of the C-shaped structure of the CF. In each compartment - rostral, dorsal and caudal - we developed the neurovascular anatomy and then discussed the clinical and surgical applications.
    Advances and technical standards in neurosurgery 01/2012; 38:97-113. DOI:10.1007/978-3-7091-0676-1_5
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    ABSTRACT: Seeding on surgical pathway is a rare form of clival chordoma treatment failure. We report the case of a 42-year-old male with a clival chondroid chordoma removed by a sublabial transsphenoidal approach followed by proton beam radiotherapy, who developed a maxillary bone recurrence 3 years after surgery.
    British Journal of Neurosurgery 09/2011; 26(1):102-3. DOI:10.3109/02688697.2011.595844 · 0.95 Impact Factor
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    ABSTRACT: Cauda equina tumours (CET) are rare and usually benign. Treatment of schwannomas and benign ependymomas, which are the most frequent histopathological types of CET, is now well established. However, management of other presumed histopathological types of CET is still a matter of debate. The aim of this study was to assess the incidence and the surgical treatment of rare CET. A retrospective study was carried out on 176 adult patients surgically treated for CET in our two departments from 1994 to 2010. We reviewed pre- and postoperative symptoms, magnetic resonance imaging aspects, surgical findings, outcome including operative neurological morbidity, local recurrence rate and operative mortality, and incidence of rare CET. Seventeen percent (30 patients) of CETs operated on were neither schwannomas nor benign ependymomas. Half of these cases were benign tumours, with paragangliomas being the most common. Two patients were in poorer clinical condition after surgery, one patient experienced a local recurrence, and one died following surgery, from the progress of his disease (Von Hippel-Lindau disease). The other half were malignant tumours, with metastases being the most common. One third of the patients were worsened by surgery, and the mortality rate was 1/3 at 8 months (1-27 months). Roughly one in six CET were neither schwannomas nor benign ependymomas. This study demonstrated the efficiency of surgery for rare benign CET with a low local recurrence rate. Surgical treatment of rare malignant CET led to a high rate of increased postoperative neurological deficit in patients with a reduced life expectancy.
    Acta Neurochirurgica 09/2011; 153(9):1787-96. DOI:10.1007/s00701-011-1094-2 · 1.79 Impact Factor
  • Neurochirurgie 09/2011; 57(s 4–6):268–269. DOI:10.1016/j.neuchi.2011.09.061 · 0.47 Impact Factor
  • S Kim · P François · E Lescanne · S Velut · D Bakhos
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    ABSTRACT: Ossifying fibroma is a rare benign fibro-osseous lesion that usually affects mandible and maxillary bone. Their localisation to paranasal sinus and skull base is uncommon. We report a huge recurrence of ossifying fibroma of the ethmoid paranasal sinus involving the skull base. Ten years after the removal of ossifying of the ethmoid 34 year old man presented headache with diplopia. Computed tomography (CT) and magnetic resonance imagery (MRI) showed a recurrent tumour witch extended to the nasal cavity, the sphenoid and the posterior ethmoid sinuses, and the skull base. The tumour was totally removed using an anterior subcranial approach with removal of the orbital rim. Histopathology confirmed an ossifying fibroma. Two years later a subdural empyema with frontal suppuration necessited to remove the frontal bone flap, which was re-constructed 12 months later using a synthetic material. Ossifying fibroma is a rare, benign tumour witch may recur if incomplete resection is performed. A long follow up with CT scan and MRI is required.
    Revue de laryngologie - otologie - rhinologie 01/2011; 132(3):177-9.
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    P Francois · E Lescanne · S Velut
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    ABSTRACT: The aim of this work was to clarify the descriptive anatomy of the optic dural sheath using microanatomical dissections on cadavers. The orbit is the rostral part of the extradural neural axis compartment; the optic dural sheath forms the central portion of the orbit.In order to describe this specific anatomy, we carefully dissected 5 cadaveric heads (10 orbits) up to the meningeal structure of the orbit and its contents. 1 cadaveric head was reserved for electron microscopy to add to our knowledge of the collagen structure of the optic dural sheath.In this chapter, we describe the anatomy of the interperiostal-dural concept and the anatomy of the orbit. The optic dural sheath contains three portions: the intracranial, the intracanalicular and the intraorbital segment. Each one has specific anatomic relations which result in particular surgical considerations.
    Advances and technical standards in neurosurgery 01/2011; 36:187-98. DOI:10.1007/978-3-7091-0179-7_7
  • P. François · Y. Nochez · S. Velut
    Neurochirurgie 12/2010; 56(6):536-536. DOI:10.1016/j.neuchi.2010.10.038 · 0.47 Impact Factor
  • Neurochirurgie 12/2010; 56(6):547-547. DOI:10.1016/j.neuchi.2010.10.072 · 0.47 Impact Factor
  • Neurochirurgie 12/2010; 56(6):538-538. DOI:10.1016/j.neuchi.2010.10.043 · 0.47 Impact Factor