Francesco Doglietto

The endoscopic extended transsphenoidal approach for craniopharyngiomas

OBJECTIVE: The endoscope has recently been applied to the supradiaphragmatic transsphenoidal approach, but only case reports dealing with different pathological features have been described. The authors present their experience with this technique in 10 patients with craniopharyngiomas. METHODS: A pure endoscopic endonasal technique was used. From November 1998 through May 2005, four males and six females with a craniopharyngioma, either purely supradiaphragmatic (six patients) or with a significant suprasellar component (four patients), were treated. The tumors had a mean diameter of 2.9 cm (range, 1–4 cm); four patients had a major prechiasmatic component and six had a retrochiasmatic one. RESULTS: Seven total, one subtotal, and two partial resections were obtained. Vision symptoms improved significantly in six out of eight patients. Endocrine function did not improve after surgery, and diabetes insipidus was the most frequent deficit, although it was transient in five out of eight patients. Cerebrospinal fluid leak was the most frequent complication and required reoperation in two patients. Postoperative obesity occurred in two patients. No recurrence has yet been documented in the total resection group. The mean follow-up period is 37 months (range, 3–75 mo). CONCLUSION: The endoscopic technique allows results comparable with the best microscopic series. We think that this technique increases the safety of the procedure because of improved vision. Further studies are required to better define the exact location of the tumor with respect to the arachnoidal plane, the extra-arachnoidal craniopharyngioma being the most suitable for a radical removal using a transsphenoidal supradiaphragmatic approach.

Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas.

CONTEXT Ki-67 is a marker of proliferation activity associated with invasiveness and prognosis in human tumors. OBJECTIVE The aim of the study was to evaluate the Ki-67 index prognostic relevance in a group of acromegalic patients who underwent transsphenoidal surgery for a GH-secreting pituitary adenoma. MATERIAL AND METHODS We selected 68 consecutive acromegalic patients referred to our hospital during a 5-yr period. The Ki-67 index was determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. Those patients who were not completely cured after surgery began medical therapy with somatostatin analogs (SSAs). Periodical pituitary magnetic resonance imaging and hormonal evaluation were performed during the follow-up. RESULTS Twenty-eight of 68 patients were cured after surgery (41%). Among the 40 patients treated with SSAs, 13 were considered uncontrolled. Pituitary magnetic resonance imaging showed residual/recurrent disease in 25 of 68 patients after 6 months. No correlation was found between Ki-67 index and age, tumor size, GH, or IGF-I plasma levels. Tumors described as having cavernous sinus invasion had a higher mean Ki-67 index as compared with noninvasive tumors (P < 0.01). The Ki-67 index was significantly lower in tumors in patients cured after surgery as compared with patients considered not cured (P < 0.01) and in tumors in patients controlled by SSA therapy as compared with patients considered as uncontrolled (P < 0.05). CONCLUSION The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first generation somatostatin analogues: an immunohistochemical study

AIM To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. PATIENTS AND METHODS SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR. RESULTS None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04). CONCLUSION The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.

MICROSCOPIC AND ENDOSCOPIC EXTRACRANIAL APPROACHES TO THE CAVERNOUS SINUS: ANATOMIC STUDY

OBJECTIVE In the past 2 decades, various extracranial approaches to the cavernous sinus (CS), using either microscopic or endoscopic techniques, have been described. The aim of this study was to describe the distinctive anatomic features of these approaches and compare their efficacy in exposing the sella and parasellar areas. METHODS Ten adult cadaver heads with red latex injected in the arterial system were used. Five different approaches were performed: 1) endonasal microscopic transsphenoidal approach; 2) sublabial microscopic transsphenoidal approach, including its variation described by Fraioli et al. (12); 3) transmaxillary microscopic approach; 4) paraseptal endoscopic transsphenoidal approach; and 5) transethmoid-pterygoid-sphenoidal endoscopic approach. The CS exposition was evaluated for each approach and a grading system, which considers surgical maneuverability as well as visualization, was used. RESULTS The medial CS compartment is well exposed with all endoscopic and microscopic transsphenoidal approaches, but it is insufficiently exposed with the transmaxillary approach. The variation to the sublabial microscopic approach suggested by Fraioli et al. allows its widest microsurgical exposure. The lateral compartment is well visualized with the transmaxillary microscopic and the endoscopic approaches. The major anatomic structures that can limit exposure of the CS lateral compartment are the posterior ethmoid and medial pterygoid process. CONCLUSION The sublabial transsphenoidal microscopic approach, with its variations, allows the most versatile extracranial microscopic exposure of the sella and CS. The paraseptal, binostril endoscopic approach allows a very good exposure of the CS; the transethmoid-pterygoid-sphenoidal endoscopic approach achieves the best maneuverability in the lateral compartment of the CS.

Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

Background and Objective: In 2004, the World Health Organization defined atypical pituitary adenomas as those with a Ki-67 expression >3%, an excessive p53 expression and increased mitotic activity. As the usefulness of this classification is controversial, we reviewed typical and atypical pituitary adenomas to compare the clinical and prognostic features. Patients and Methods: We retrospectively reviewed 343 consecutive pituitary adenomas. Atypical pituitary adenomas represented 18.7% of cases. All patients were operated on at the Department of Neurosurgery of our institution and were followed up at the Hypothalamic-Pituitary Disease Unit of the same institution. The median follow-up time was 75 months (range 7-345). Results: Younger age at diagnosis as well as immunohistochemical positivity for adrenocorticotropic hormone and prolactin correlated with a higher risk of atypical pituitary adenomas, whereas typical and atypical pituitary adenomas did not differ with regard to gender, tumor size, recurrence risk and disease-free survival time (DFST). Among the 219 patients who underwent radical surgery, a Ki-67 expression ≥1.5% was associated with a higher risk of recurrence and a worse DFST, even after correction for age at diagnosis, gender, immunohistochemical classification, tumor size, invasiveness and Knosp classification [p = 0.01; hazard ratio (HR) 2.572; 95% confidence interval (CI) 1.251-5.285). Pituitary adenomas with a Ki-67 expression ≥1.5% showed a worse DFST as compared to pituitary adenomas with a Ki-67 expression <1.5% (HR 2.166; 95% CI 1.154-4.064). Conclusion: In this series, atypical and typical pituitary adenomas did not differ with regard to recurrence and DFST. Pituitary adenomas with a Ki-67 expression ≥1.5% showed a higher recurrence risk and a worse DFST as compared to those with a Ki-67 expression <1.5%. We suggest that a Ki-67 expression ≥1.5% may be useful as a prognostic marker, though this will need to be confirmed by prospective, multicenter data.

Communicating hydrocephalus following surgery and adjuvant radiochemotherapy for glioblastoma

OBJECT Communicating hydrocephalus is an uncommon complication in patients treated for glioblastoma multiforme (GBM). Its pathogenesis remains unclear. The authors evaluated the clinical and radiological factors associated with the onset of communicating hydrocephalus and the impact of ventriculoperitoneal (VP) shunt surgery on the outcome of these patients. METHODS One hundred twenty-four patients harboring GBM, who had undergone craniotomy for tumor resection and adjuvant radiochemotherapy, were retrospectively assessed. Seven of them developed communicating hydrocephalus and were treated with VP shunt surgery. Clinical and radiological estimates included Karnofsky Performance Scale (KPS) score, previous surgery, overall survival (OS), CSF pressure and components, tumor location, and leptomeningeal dissemination. RESULTS All 7 patients who developed communicating hydrocephalus had undergone at least 2 craniotomies for tumor resection before the onset of hydrocephalus (p = 0.0006; Fisher exact test). Six cases showed high levels of CSF proteins. There was a highly significant relationship between ventricular opening at surgery for tumor recurrence and onset of hydrocephalus (p = 0.0002; Fisher exact test). In these patients, VP shunt surgery was followed by a significant improvement of KPS score (p = 0.0180; Wilcoxon signed-rank test). The median OS after VP shunt insertion was 5 ± 2.9 months. CONCLUSIONS Ventricular opening after radiochemotherapy and high CSF protein levels are significant predictors of communicating hydrocephalus in patients with GBM. The VP shunt surgery improves quality of life in these patients.

Olfactory groove meningioma: report of 99 cases surgically treated at the Catholic University School of Medicine, Rome.

OBJECTIVE We reviewed our series of olfactory groove meningiomas (OGMs) with the aim to relate the surgical approach with outcome and to define clinical and pathologic predictors of prognosis. METHODS Ninety-nine patients who underwent 113 craniotomies at our Institution between 1984 and 2010 were entered this study. The relationship between surgical approach (bifrontal, fronto-orbito-basal, and pterional) and either tumor diameter, extent of tumor resection, complication rate, need of reoperation, and Karnofsky Performance Status (KPS) was analyzed. The impact of age (≤ 70 vs. > 70 years), sex, tumor diameter (< 6 vs. ≥ 6 cm), pre- and postoperative KPS (< 80 vs. ≥ 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed. RESULTS The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). The risk of life-threatening complications trended to be lower in patients operated upon either via the fronto-orbito-basal and via the pterional approach than in those treated via the bifrontal approach. Retraction-related brain swelling did not occur in any case after the fronto-orbito-basal approach (P = 0.0384); however, this approach was associated with a greater rate of cerebrospinal fluid leak (P = 0.0011). Among prognostic factors, age ≤ 70 years (P = 0.0044), tumor diameter <6 cm (P = 0.0455), pre- and postoperative KPS ≥ 80 (both P < 0.0001), Simpson grade I-II (P = 0.0096), and WHO histologic grade I (P = 0.0112) were significantly associated with longer overall survival. Age (P = 0.0393) and WHO histologic grade (P = 0.0418) emerged as independent prognostic factors for overall survival on multivariate analysis. CONCLUSION In the largest series of OGMs published to date, the bifrontal approach was associated with a greater risk of life-threatening complications compared with the lateral pterional and fronto-orbito-basal approaches. The fronto-orbito-basal approach provided greater chances of total tumor removal than the bifrontal and pterional approaches. Two independent factors for overall survival of patients with OGM were identified, namely age and WHO grade.

Retrospective analysis of variables favouring good surgical outcome in posterior epilepsies

Aimto determine variables favouring good surgical outcome in posterior epilepsies.MethodsFourteen patients submitted to epilepsy surgery were included in the study. The epileptogenic zone was located in temporo–parieto–occipital areas as assessed by both invasive and non-invasive pre–surgical evaluation. Several variables (age at first seizure; age at surgery; disease duration; type, frequency and clinical semiology of seizures; presence of lesion; scalp ictal and interictal EEG; localization and extension of epileptogenic zone; completeness of surgical resection) were compared (Fisher’s exact test) with freedom from seizures to determine whether surgical outcome (Engel’s classification) could be related to any of them.ResultsSeven patients were seizure free (Ia) and very satisfying results were obtained for 3 patients (2 Ib, 1 Ic). New post–surgical visual deficits occurred only in 3 patients. Surgical outcome was related significantly to two variables: scalp ictal EEG (focal versus non–focal; p: 0.014) and completeness of surgical resection of epileptogenic zone (p: 0.0023). A significant trend towards a better outcome for focal interictal intracranial activity versus a nonfocal one (p: 0.07) was found.ConclusionsThe correlation between completeness of epileptogenic zone resection and surgical outcome suggests that a presurgical protocol, allowing a precise definition of the area of resection, could help in obtaining more satisfying results in posterior epilepsies.

Pituitary Carcinoma: A Devastating Disease in Need of an Earlier Diagnosis and of Effective Therapies

P ituitary adenomas represent the third most common intracranial tumor (15) and are therefore the mainstay of our daily practice. Pituitary surgery can be extremely successul, as we are increasingly able to cure devastating disorders such s Cushing disease and acromegaly. Nonetheless, even in the ra of endoscopy, neuronavigation, and other technologies that ave advanced the boundaries of pituitary surgery, every surgeon s aware of the limits of surgical treatment: interdisciplinary ollaboration is indeed part of every center encountering pituitary athologies. The multidisciplinary approach, which includes at east the endocrinologist and radiotherapist, leads to disease ontrol in many circumstances that cannot be controlled solely by urgery. Unfortunately, however, some situations are still exremely frustrating because young patients, who harbor apparntly benign tumors, escape treatment; once the singular aggresivity of the tumor is evident, not infrequently it is also clear that ur therapeutic chances are already gone: this is the most requent case scenario of pituitary carcinomas, a rare condition, ith approximately 150 cases reported in the literature. In this ssue, Shastri et al. add another patient to the literature.

Motoneurons innervating facial muscles after hypoglossal and hemihypoglossal-facial nerve anastomosis in rats.

Abstract Hypoglossal-facial nerve anastomosis (HFA) is the most popular surgical procedure to reinnervate facial muscles after injury of the facial nerve. Section of the hypoglossus causes paralysis and atrophy of the hemi-tongue. In the attempt to overcome this consequence, the hemihypoglossal-facial nerve anastomosis (HHFA) has been proposed and only a half of the main trunk of the hypoglossus is connected to the distal stump of the facial nerve. In the rat, we have studied experimentally the anatomical nuclear changes after HFA and HHFA with the aim of establishing the quantitative motoneuron innervation of facial muscles obtained with each one of the two operative options. Horseradish peroxidase (HRP) injected in both types of anastomosis labeled not only hypoglossal motoneurons, but also facial motoneurons. HFA appeared to offer a significant quantitative motoneuron innervation higher than HHFA and then a higher probable better functional recovery. Both HFA and HHFA performed immediately after section of the facial nerve in rats did not result in a phenomenon of motor hyperinnervation. In our experimental model, the proximal facial nerve stump was coagulated at the stylomastoid foramen to avoid regeneration. Then, the labeled motoneurons into the facial nucleus could really be the expression of axonal projections from facial motoneurons to the hypoglossus nerve and facial muscles. No labeled motoneurons were seen contralaterally as we observed previously after section and repair of several nerves.