A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

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.

Submandibular gland endoscopic resection: a cadaveric study.

Recent advancement of head and neck surgery has been marked by the development of endoscopic and video-assisted minimally invasive surgery. This study reports the feasibility of endoscopic submandibular gland resection in human cadavers. Twelve submandibular gland resections were performed in six human cadavers. A 30 degrees angle endoscope and conventional surgical instruments were inserted through two 15 mm submandibular incisions. Dissection was carried out bluntly with scissors in an avascular plane superficial to the gland. No insufflation was needed since transcutaneous sutures lead to effective retraction. Facial vessels, the lingual nerve and Wharton's duct were identified and protected. Vascular ligatures were performed using surgical miniclips. After the procedure, an open submandibular dissection was performed to control the integrity of the anatomical structures. In all cases, the resection of the submandibular gland was successful without the need for an additional incision. Injuries of the facial artery and lingual nerve occurred when the procedure was carried out initially. The operative time decreased with training, from 120 min for the first cases to 35 min for the later ones. In conclusion, endoscopic submandibular gland resection is possible without major difficulty. Training and experience reduce the operative time and the complication rate.

Morphological cervical disc analysis applied to traumatic and degenerative lesions.

Trauma and degenerative pathologies at the lower cervical spine are different from lumbar spine pathologies. However, the description of cervical discs is classically taught similarly to that of the lumbar discs. Recent studies have raised this issue, and in 1999, Mercer and Bogduk described ventral annulus fibrosus as a crescent-shaped interosseous ligament. We propose a metric analysis of the different components of the cervical disc to examine this description. We analyzed 140 sagittal and coronal transections of 35 discs. These discs were taken from seven cervical spines at the five lower levels, C2-C3, C3-C4, C4-C5, C5-C6 and C6-C7. We measured quantitative parameters on sagittal, para-sagittal, ventral coronal and dorsal coronal colored transections: disc length (L), ventral annulus thickness (VAF), lateral annulus thickness (LAF), dorsal annulus thickness (DAF), length of the fibrocartilaginous tissue (FC), sagittal and coronal fibrocartilaginous core ratio (% Core) and intra-disc cleft length (Cleft). We also measured two qualitative parameters: degenerative disease of cartilaginous end plates and total intra-disc cleft. Finally, we examined 114 transections, and 18.5% were ruled out. The results showed thick ventral annulus fibrosus, thin lateral annulus and a very thin dorsal annulus. Fibrocartilaginous tissue filled the dorsal sagittal half of the disc. Intra-disc cleft split the fibrocartilaginous tissue and spread through the ventral annulus only six times. The shape of the ventral annulus at the lower cervical spine is compared to a pivot-hinge device. The aspect is functionally discussed in regard to teardrop fractures, unilateral locked facet syndrome and degenerative changes in the unco-vertebral area.

[Reconstruction after tumor resection of the anterior skull base with an of abdominal fat graft]. / Reconstruction après résection tumorale de la base antérieure du crâne par greffon graisseux abdominal.

OBJECTIVES: Reconstruction of the anterior skull base is a surgical stage as significant as tumor removal. The quality of the reconstruction is the primary determinant of postoperative mortality, morbidity. The aim of our work was to assess the results of a reconstruction process combining: 1) a pericranium graft held by biological glue to complete the dura mater; 2) an abdominal fat graft supported by a Silastic arch to maintain the neurological structures. PATIENTS AND METHODS: This was a retrospective study. 55 patients (44 men and 11 women), 59 mean age (14 - 78), were analyzed. 45 had a malignant tumor and 10 a benign tumor. 35 patients were treated using a mixed approach and 18 using a trans frontal-sinus approach alone. Forty-three patients treated for a malignant tumor underwent postoperative radiotherapy. Results were analyzed according to 3 periods: 1) immediate postoperative period (<25 days); 2) early postoperative period (25 days - 3 months); 3) late postoperative period (> 3 months). RESULTS: None of the patients were lost to follow-up. The average follow up was 84 months. All periods considered together, we had five (9.4%) graft infections, 6 (11.3%) CSF leaks and 1 (1.8%) cases of meningitis. CONCLUSION: We use a simple technique for reconstruction. Postoperative complications were exceptional, even after postoperative radiotherapy. Medium and long-term results are good and similar to those obtained with other processes used for reconstruction of the anterior skull base reconstruction.

[Role of perioperative biological tests during the performance and follow-up of corticotroph adenoma exeresis]. / Place des examens biologiques peropératoires dans la réalisation et le contrôle de l'exérèse des adénomes corticotropes.

ACTH assay in cavernous sinus samples during resection of pituitary adrenocorticotroph adenomas is a simple and safe technique providing an intraoperative assessment of adrenocorticotroph hormone gradients. Bilateral puncture of the cavernous sinus can be achieved vial the standard transsphenoidal approach to the sella turcica. ACTH is determined with IRMA at 37;C with an incubation time of less than one hour. Among 71 cases in our experience, the ACTH gradient accurately predicted the position of the adenoma in 93% of the cases. This rate is higher than the 61% accuracy reported for inferior petrosal sinus sampling. The technique reported is more precise than MRI which correctly identifies adenomas in only 50% of the cases. The remaining cases are either false positives or false negatives. We report an 82% cure rate either via direct resection of the microadenoma or via partial hypophysectomy guided by the ACTH gradient. In our series, 20 cases of Cushing's disease had a normal MRI and no surgically identifiable adenoma. In 10 of these cases however, cure was achieved by performing ACTH gradient guided partial hypophysectomy. This method produces no morbidity and is most helpful for the neurosurgeon allowing confirmation of the position of an MRI-visible adenoma or an adenoma identified intraoperatively. It does not however replace neurosurgical experience which remains the most important predictive factor for outcome in surgical treatment of Cushing's disease.

Endonasal endoscopic closure of cerebrospinal fluid rhinorrhea.

The authors review their experience with endoscopic repair of skull base defects associated with cerebrospinal fluid (CSF) rhinorrhea involving the paranasal sinuses. A total of 22 patients was treated endoscopically between 1992 and 1998. The repair method consisted of closure of the CSF fistula with a free autologous abdominal fat graft and fibrin glue, supported with a sheet of silastic. The primary closure rate was 82% (18/22), and the overall closure rate was 95.5% (21/22) without recurrence or complications within an average follow-up of 5 years (14-83 months). A single patient still complains of cerebrospinal rhinorrhea, although this was never proved by any clinical, endoscopic, or biological (beta(2)-transferrin) examination. The repair of ethmoidal-sphenoidal cerebrospinal fluid fistulae by endonasal endoscopic surgery is an excellent technique, both safe and effective. Fat is a material of choice, as it is tight and resists infection well. The technique and indications for endoscopic management of cerebrospinal fluid leaks are discussed.

Management of craniocervical junction dislocation.

The discovery of a craniocervical junction malformation requires management in three steps: (1) The patterns must be recognized using tomographic measurements (Chamberlain's line, Wackenheim's line). Dynamic flexion-extension studies are necessary to assess stability or instability. Stable patterns range from platybasia to basilar invagination, with gradual deformation, and are frequently associated with Chiari malformation. Unstable patterns characterized by odontoid instability are the equivalent of an odontoid fracture. The origin is malformative (hypoplasia, aplasia of the dens, os odontoidum), but the last may be difficult to distinguish from an old odontoid fracture. They are found in many syndromes (Down, Morquio, etc.). Unstable atlantoaxial patterns with atlas assimilation are hardly reducible; they evolve toward progressive instability. (2) The neurological consequences must be defined from the clinical features of the spinal cord and the cranial nerves. Both static and dynamic MRI scans must be performed; in this way identification of the neural abnormalities (hydromyelia, Chiari, etc.) and of the osseous compression is possible. (3) The most appropriate operative procedure must be selected: stable platybasia with a nervous compression by Chiari is cured only by posterior decompression; odontoid instability is cured by reduction and posterior fixation, using hooks and autologous bone grafts on the posterior arches of C-1 and C-2. Sometimes a transarticular screw fixation of C1-2 is necessary if there is a defect on the C-1 posterior arch. Craniocervical dislocations with assimilation of the atlas require posterior occipito-vertebral bony fixation with grafts and external halo immobilization or internal fixation with hooks or screws, with anterior transoral decompression in a second step.

[Unusual approaches to hypophyseal adenomas]. / Les voies d'aboard inhabituelles des adénomes hypophysaires.

For pituitary adenomas surgery, rhinoseptal transsphenoidal approach is used in 98 to 99% of the cases. Although this approach is fitting for microadenomas and the majority of macroadenomas, some of them develop extensions in the nasal fossas, the posterior cranial fossa, the suprasellar region, or into the cavernous sinus and will require other approaches. For the superior routes, the frontopterional approach gives good control of the suprasellar region, the anterior and middle base of the skull. The tumor dissection is performed inside the concavity of the chiasm and between the internal carotid artery and the optic nerve (optico-carotid approach). The frontopterional approach is used for superolateral extensions, especially in the lateral fissure. The bifrontal basal inter hemispheric approach, through a medial frontal bone flap tangential to the base, gives a good route to the suprasellar region and behind the dorsum, and also for tumors extended in the third ventricle in case of prefixed chiasm. For the inferior routes, the participation of ENT or craniofacial surgeons is a great help. The transfacial or transethmoidal approach performs a hollowing of the nasal fossas and gives a large interorbital tunnel adapted for tumors extended in the rhinopharynx and the ethmoid. The Le Fort I maxillary osteotomy offers also a large approach for adenomas extending in the rhinopharynx. The transcavernous approach from Dolenc, for adenomas progressing in the cavernous sinus requires a long and difficult procedure. The progression of some adenomas in many directions may require a combined approach in one or two procedures.

Severe head injuries: an outcome prediction and survival analysis.

OBJECTIVE: To identify the predictors determined early after admission and associated with unfavorable outcome or early (within 48 h) death after severe head injury. DESIGN: Prospective cohort study. SETTING: A neurosurgical intensive care unit in a university hospital. PATIENTS: 198 consecutive comatose patients hospitalized from 1989 to 1992. RESULTS: Logistic regression showed that a combination of age, best motor response score from the Glasgow Coma Scale, and hypoxia provided a good prediction model of unfavorable outcome (sensitivity = 0.93). The length of participation of survivors was 6 to 61 months (median 27.1). The Cox model demonstrated age, motor score less than 3, mydriasis, and hypoxia as poor prognosis factors. CONCLUSIONS: Clinicians can determine the odds of a good outcome from the combination of three easily measurable factors using a simple diagram constructed from logistic regression. Survival analysis showed that motor score adjusted values greater than 3 had the same prognosis.

The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients--results of the NBL 90 Study of the French Society of Pediatric Oncology.

BACKGROUND: Neuroblastoma is the most common malignant cause of spinal compression in the pediatric population. More than 30% of patients who are impaired prior to treatment remain impaired after the completion of therapy. Those who do not improve after decompressive laminectomy may go on to develop severe delayed spinal deformities. METHODS: To decrease the long term sequelae of routine neurosurgical intervention for all intraspinal extensions of neuroblastoma, the French NBL 90 Study was formulated to use chemotherapy as a first-line treatment for all nonmetastatic neuroblastomas with intraspinal extension. Neurosurgical decompression and excision was recommended only for patients demonstrating rapid neurologic deterioration. RESULTS: The overall survival of the 42 patients registered was 97%. Initial neurologic impairment was present in 27 patients (64%), including 11 with paraplegia. Thirty-two patients received chemotherapy as first-line treatment. Complete regression of the intraspinal component was observed in 13 patients and partial regression of greater than 50% of the initial volume in 5 patients. Of 19 evaluable patients presenting with a neurologic deficit and treated with primary chemotherapy, recovery was completed in 11 and partial in 3. Four patients failed to recover from long-standing pretreatment paraplegia. Only one patient worsened during therapy, and recovered completely after emergent neurosurgical intervention. Seven patients underwent initial neurosurgical procedures; six had a neurologic deficit and five recovered completely, including all three who presented with acute onset of paraplegia. Three patients had extraspinal surgery as exclusive treatment. Six patients (15%) suffered severe neurologic sequelae. Only one of the patients who underwent surgery required spinal stabilization for progressive deformity, but follow-up is limited. CONCLUSIONS: By treating patients with dumbbell neuroblastoma initially with chemotherapy, the authors were able to reduce the size of the intraspinal mass in 58% of patients, improve partial neurologic deficits in 92%, and avoid neurosurgical decompression in 60%. Neurologic deficits also improved in 83% of patients requiring emergent neurosurgical intervention.

[Surgical treatment under endoscopic control of cerebrospinal fluid rhinorrhea of sphenoid origin. A propos of 5 cases]. / Traitement chirurgical sous contrôle endoscopique des rhinorrhées cérébrospinales d'origine sphénoïdale. A propos de 5 cas.

From 5 to 15% of cerebrospinal fluid (CSF) leaks come from the sphenoid, subdivided in two groups: traumatic and spontaneous. Many surgical approaches are used for their treatment, with consistent morbidity. Five sphenoidal CSF leaks (3 traumatic and 2 spontaneous) were operated only by endoscopic endonasal route from 1993 to 1995, after endoscopic and computerized tomography (CT) scan evaluation. A sphenoidotomy by a simple endonasal route through the spheno-ethmoidal recess was performed in 3 cases. In the other 2 cases, the sphenoidotomy required a trans-ethmoidal approach through the posterior part of the ethmoid. After identification of the leak and the removal of mucosa, the sphenoid sinus was filled up by abdominal fat kept in place by biological glue and supported by a silastic sheat. No post-operative complication appeared. The median duration of hospitalization was 6.5 days (5-13). During the follow-up (19.5 months, 8-30), 4/5 complete remission was observed. The last case needed a second obturation at 11 months, due to a retraction of the fat, without recurrence. This endonasal endoscopic approach is safe and efficient for leaks closure, with no morbidity compared with others invasive approaches.

[MRI aspects of cerebellar hemangioblastomas. Apropos of 9 cases]. / Aspect IRM des hémangioblastomes cérébelleux. A propos de 9 observations.

Nine patients with haemangioblastoma of the posterior cerebral fossa were explored by computerized tomography (CT), then by magnetic resonance imaging (MRI) with enhancement by gadolinium in 4 cases. Following a review of clinical and laboratory data, the radiological images are detailed and distributed into three forms: cystic with mural nodule, solid, and annular. The usefulness of the different imaging techniques is specified, and the stress it put on the need to look for multiple sites in the entire central nervous system.

Blood supply of the olfactory nerve. Meningeal relationships and surgical relevance.

The authors report the results of a series of dissections and anatomic sections of the fronto-basal region of the brain and of the anterior cranial fossa in human cadavers. The constant presence of an arachnoidal cistern above the olfactory nerve was verified. The arachnoid separates from the pial membrane and forms a bridge with the ventral part of the olfactory bulb and tract, from the lateral edge of the olfactory sulcus to the medial edge of the gyrus rectus. The cistern is wide in its anterior portion, between the gyrus rectus and the olfactory bulb, and is reduced to a virtual slit in its posterior portion where the tract is lodged in the olfactory sulcus. The olfactory nerve can be separated without damaging fronto-basal arachnoidial adhesions over several centimeters. Dissection of this region after intravascular injection of colored media shows the constant presence of an artery destined to the olfactory bulb and tract. It originates either from the lateral surface of the anterior cerebral a. (segment A2), or from the medial fronto-basal a., and consistently provides terminal branches in front of the olfactory trigone in the medial olfactory sulcus. At their ventral extremity, the olfactory structures are therefore vascularised independently for several centimeters, from the lower face of the frontal lobe. The independent vascularisation of the olfactory nerve, the tenuous and easily detachable adhesions, and the actual presence of a true arachnoidal cistern all contribute to enabling surgical techniques which conserve olfactory function during anterior approaches.

[Role of hormonal exploration in avoiding of the failures of anterior pituitary gland surgery in Cushing disease]. / Rôle de l'exploration hormonale dans l'esquive des échecs de la chirurgie anté-hypophysaire de la maladie de Cushing.

Patients with Cushing's disease are not cured by transsphenoidal microsurgery in about 30% of the cases. Beside the problem of invasive macroadenomas, these failures are due either to diagnostic errors, or to very small microadenomas that could no be found. Positive diagnosis of hypercortisolism is quite straightforward and the problem is sensitivity rather than specificity. Primary adrenocortical hypercortisolism should not be mistaken. Depression-related hypercortisolism can be difficult to distinguish from Cushing disease: most cases are recognized after clinical story and CRF stimulation test. Ectopic ACTH secretion by a carcinoid tumor represents at least 8% of ACTH-dependant hypercortisolism. It cannot be reliably distinguished from corticotroph microadenoma by either classical dynamic tests or anterior pituitary imaging. However measurements of ACTH in the inferior petrosal sinus under basal condition and CRF stimulation allow the diagnosis of central or peripheral ACTH secretion with a quasi 100% sensitivity and specificity. In contrast this technique is of poor help for the diagnosis of lateralization of corticotroph microadenomas, for which it gives erroneous results in 25 to 50% of the cases. Rapid intraoperative measurement of ACTH in peripituitary blood seems a more reliable approach. In our series it gave correct results in 11 out of 12 cases. In 1995 hormonal exploration of Cushing disease should limit the failures of anterior pituitary surgery to the cases of invasive macroadenomas that cannot be completely removed.

Intracranial plasma cell granuloma: a report of four cases.

Inflammatory pseudotumors (IPT) are rare lesions composed of inflammatory cells admixed with collagen tissue. Although IPT are ubiquitous, intracranial locations are rare. In this study, four intracranial IPT of the plasma-cell-granuloma (PCG) type are reported. Four patients presented with lesions located, respectively, in the right cavernous sinus, the left cavernous sinus with extension to the tentorium cerebelli, the vermis cerebelli, and the pituitary stalk. All patients were operated on, but complete resection could not be achieved in cases 1 and 2. Follow-up was favorable in all cases, although case 1 still complained of headaches 2 years after operation. All cases were studied on histologic and immunohistochemical bases, and ultrastructural analysis was performed on two cases. In cases 1, 2, and 4, IPT were made up of plasma cells admixed with lymphocytes and rare histiocytes in a fibrous tissue-the density of which varied from case to case. In case 3, the mass was composed of plasma cells associated with numerous foamy histiocytes and polymorphonuclear cells. No light chain restriction could be demonstrated when immunohistochemistry was performed, and ultrastructural study did not disclose features reminiscent of meningioma or histiocytosis X. Intracranial IPT should not be confused with other diseases such as meningioma, lymphoproliferative disorders, or histiocytosis X. Although intracranial locations are much rarer than pulmonary ones, histology is identical in both sites and shows different patterns in its evolution. This is in agreement with the inflammatory origin of this lesion.

[Corneatopic evaluation in the trigeminal ganglion of the rat]. / Approche de la topie cornéenne dans la ganglion trigéminal du rat.

Cornea is only innervated by free nerve endings. A corneal scarification exposes free nerve endings which are able to transport True Blue and Fast Blue dyes by retrograde axonal transport. These tracers label the perikaryon. A few days later, the rats are sacrificed and perfused with an intra cardiac 10% formaldehyde perfusion in a phosphate buffer. The analysis of ipsilateral semi lunar (trigeminal) ganglion with a Leitz Dialux fluorescence Microscope shows fluorescent blue cells. The organization of these cells in the volume of the ganglion has been determined by selective labelling of each corneotopic zone in the supero-internal quarter of the rat trigeminal ganglion. Data from the literature about the somatotopic organisation of the other parts of the rat face are in agreement with these results.

[Evaluation of dermatomes in the hind paw of the rat using retrograde axonal transport]. / Evaluation des dermatomes de la patte postérieure du rat par méthode de transport axonal rétrograde.

UV light fluorescent tracers (True Blue and Fast Blue) are placed in contact with sensitive receptors after dermabrasion. The abraded surfaces are limited to two hemidorsal areas and two hemi plantar areas on the animals' foot. A five days survival is allowed to enable the axonal retrograde transport of the tracers, then the animals are sacrificed and perfused with an intracardiac injection of 10% formaldehyde in phosphate buffer at 7.4 pH. The lumbar spinal ganglions are immediately dissected out, examined as a whole with a Leitz Dialux fluorescence microscope, then frozen and cut with a cryotome. The results of this analysis show that: i-only ipsilateral dorsal root ganglions are labeled by blue dye. ii-the number of fluorescent cells varies between 20 to 60 per ganglion. iii-a map of the distribution of the dermatomes on the rat hind foot can be deducted from the study of the labelled ganglions. They spread from L2 to L5 from the cranial to the caudal part, and from the medial to the lateral side of the rat foot, on both dorsal and plantar areas.