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.

[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.

Serotoninergic, noradrenergic, and peptidergic innervation of Onuf's nucleus of normal and transected spinal cords of baboons (Papio papio).

We have investigated with light and electron microscope immunocytochemistry the aminergic and peptidergic innervation of Onuf's nucleus in adult baboons. This nucleus, located in the ventrolateral part of the sacral spinal cord (S2 and S3), is considered to control urethral and anal sphincters and penile muscles. By comparison of intact and transected spinal cords, we have found that serotoninergic innervation has two origins: first, supraspinal, innervating the whole nucleus, with a possible predominance in the dorsal half; and second, intraspinal, corresponding to the ventral half of the nucleus. Thyrotropin-releasing hormone innervation appears largely coincident with serotonin, both in intact and transected spinal cords. Noradrenaline is exclusively of supraspinal origin, as attested by its disappearance below the level of the section. Substance P, calcitonin gene-related peptide, and Leu- and Met-enkephalin, which profusely innervate Onuf's nucleus, are on the contrary not affected by the transection. They most likely originate from the cord itself or the dorsal root ganglia. Thus, Onuf's nucleus innervation in the baboon arises both from supraspinal and intraspinal sources. The present study provides an anatomical basis for both voluntary and reflex controls of excretory and sexual functions in a primate. The same neurotransmitter (serotonin) according to its cell origin and discrete topography could exert different influences upon the same effector system.

Evidence for the existence of L-dopa- and dopamine-immunoreactive nerve cell bodies in the caudal part of the dorsal motor nucleus of the vagus nerve.

The precise neurochemical nature of tyrosine hydroxylase-immunoreactive neurons lying in the caudal part of the dorsal motor nucleus of the vagus nerve of the rat has been identified by immunohistochemistry of the catecholamines themselves. This region corresponds precisely to the area where tyrosine hydroxylase has been previously shown to be colocalized with choline acetyltransferase. Adjacent serial cryostat sections from the medulla oblongata and from the cervical spinal cord were treated either for choline acetyltransferase immunohistochemistry, aromatic L-amino acid decarboxylase and tyrosine hydroxylase immunolabelling or for tyrosine hydroxylase, dopamine, noradrenaline and L-dihydroxyphenylalanine (DOPA) immunostaining. The procedure involved the peroxidase-antiperoxidase method and an intensified diaminobenzidine reaction with imidazole. While no noradrenaline-positive cells were detectable in the dorsal motor vagal nucleus, tyrosine hydroxylase-, dopamine- and DOPA-immunoreactive perikarya were seen in the medial half of this nucleus, caudally the obex level. These results led us to conclude that these tyrosine hydroxylase-positive cells were effectively of dopaminergic nature and therefore that dopamine is a neurotransmitter contained in some neurons of the dorsal motor vagal nucleus. In the light of previous data showing colocalization of tyrosine hydroxylase and choline acetyltransferase in neurons of this portion of the nucleus, colocalization of dopamine with acetylcholine appears most likely. This might shed some light on the physiological consequences of dopamine action at target parasympathetic organs, such as the gastrointestinal tract.

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.

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.

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.

[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.

[Catheterization of the inferior petrosal sinus. Its role in the diagnosis of Cushing's syndrome. Experience with 23 explorations]. / Le cathétérisme des sinus pétreux inférieurs. Sa place dans le diagnostic du syndrome de Cushing. Expérience de 23 explorations.

Selective catheterization of the inferior petrosal sinus has been performed in 23 patients: 11 Cushing's disease, 5 lung carcinoid tumors whose diagnosis has been confirmed by surgery and 7 ACTH-dependent hypercortisolism whose final diagnosis has not yet been proved. The pituitary origin of hormone secretion is accepted if the central-to-peripheral ratio (C/PR) is equal or greater than 2 on basal values and/or during CRF test. On basal values, all subjects but one with confirmed pituitary lesions exhibited a C/PR > or = 2; the carcinoid tumors never exceeded the value of 1.3. After CRF injection, all the pituitary tumors showed an increase in C/PR; one patient with a lung carcinoid tumor (CRF-negative) showed a pituitary ACTH secretion (C/PR = 3.7). The localization of pituitary adenoma by the lateralization of hormone secretion is disappointing, except, perhaps, for very small extremely lateral adenomas. No accident occurred in our series, nor in the literature. This investigation seems the most reliable approach to prove the pituitary origin of hormonal hypersecretion. We recommend it to be performed in ACTH-dependent Cushing's syndrome when the secretory pattern is not typical and/or pituitary imaging is normal.

[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.

[Technical considerations on lumbar disk surgery. Results of a survey of 49 centers]. / Considérations techniques sur la chirurgie discale lombaire. Résultats d'une enquête portant sur 49 centres.

The lumbar discectomy, how do you see it? That could be the title of this inquiry which 49 neurosurgeons answered. At first we discuss the timing of the operation (as a rule sooner than the conventional indication of the third month) the use of operative microscope which is still uncommon (11 surgeons out of 49) and the operative policy. The more specific technical features regarding the different stages of the operation are then analysed. Opinions of neurosurgeons differ on many points particularly on the ligament and bone removal which exposes the disco-radicular conflict: whereas one third of the neurosurgeons refuse to open the lumbar facet joint, one third always open it widely and the remaining third take a mid-way position. On the whole, this inquiry points cut both a great diversity in technical details, but also a stagnation because this operation hardy improved and only slightly benefited from the technical progress.

[Spontaneous hematoma of the cerebellum]. / L'hématome spontané du cervelet.

Forty spontaneous cerebellar hematomas have been observed in 39 patients whose age ranged from 13 to 82 years, 26 being older than 60. Arterial hypertension is the most frequent aetiological factor. Amongst the other causes, vascular malformations, which may also be present in older people, anticoagulant therapy, metastatic tumor, sepsis were found; one case remained unsolved. Diagnosis is no longer a challenge since the introduction of C.T. scan, whilst M.R.I. may give most valuable informations concerning aetiology, especially when a vascular malformation is present. In this study, the influence of the hematoma size and of hydrocephalus on consciousness was demonstrated; development of hydrocephalus is favoured by the size and by a rather median location of the hematoma. In the future, M.R.I. should give better precisions concerning an eventual extension of the hemorrhage to the brainstem. The purpose of surgical treatment is twofold: alleviating brainstem compression and correcting hydrocephalus; yet, divergent opinions have been put forward in retrospective studies, concerning evacuation of the hematoma and drainage of hydrocephalus. In this series, direct attack doesn't seem to be indicated in hematomas less than 3.5 cm diameter, unless a causal lesion has to be removed. The ideal moment for hematoma evacuation is, finally, dictated by the clinical status and its evolution; however, the authors prefer, if possible, to delay it for at least 48 hours. Amongst the 39 patients, 14 deceased; of the 25 survivors, 19 were autonomous, 7 being nearly asymptomatic, 6 patients remained handicapped. Consciousness is a main prognostic factor, whilst coma in the first hours has a clearly unfavourable significance.

[Segmentation of the lumbar radicular canal]. / La segmentation du défilé radiculaire lombaire.

The lumbar CT horizontal sections identification requires three levels to be defined of each vertebra: The arthropedicular level (upper third) describes an (omega) at the back with its dense bone structures. At each side of the canal is the upper part of the lateral recess, the narrowest and therefore the most threatened part of the nerve root passage. The isthmopedicular level (middle third) describes a complete bone ring around the vertebral canal. On this non articular level, the congenital dysplasia is most clearly observed. The subpedicular level (lower third) with its muscular surrounding, shows a floral outline. A fourth level, intervertebral or discal, is added. It is very similar to the last one and of course is the most common point of disco-radicular conflict. Each level appears to be specific, both by the silhouette outlined by the ligament and bone structures and by the relationship which they have with the meninges. Each of them has its own pathology which precisely directs the surgical approach.

[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.

[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.

[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.