Nicola Boari

Results of Transsphenoidal Surgery in a Large Series of Patients with Pituitary Adenoma

OBJECTIVE: To report the efficacy and safety of microsurgical transsphenoidal surgery in a series of previously untreated patients with pituitary adenoma. METHODS: One thousand one hundred forty consecutive patients undergoing transsphenoidal resection of a pituitary adenoma at our department from January 1990 through December 2002 were included in our study. Postoperative results were classified uniformly during the period of the study. Patients were considered in remission of disease when strict hormonal and radiological criteria of cure were met. RESULTS: The most frequent tumor type was clinically nonfunctioning adenoma (NFPA) (33.2%), followed by growth hormone-secreting adenoma (28.1%), adrenocorticotropin-secreting adenoma (23.0%), prolactin-secreting adenoma (13.2%), and last, thyrotropin-secreting adenoma (2.5%). The patient population was 59.7% female and 40.3% male. Mean age was 43.0 ± 0.4 years. There were 788 macroadenomas (69.1%), and in 233 patients (20.4%), the tumor invaded one or both cavernous sinuses. The overall rate of early surgical success was achieved in 504 (66.1%) of the 762 patients with a hormone-active adenoma. Surgical outcome was better in patients with microadenomas than in patients with macroadenomas (78.9% and 55.5%, respectively), whereas tumors invading the cavernous sinus had a poorer outcome (7.4%). In patients with NFPA, no residual adenoma was present in 234 patients (64.8%). Normalization of visual defects occurred in 117 (40.5%) of the 289 patients with visual disturbances and improved in another 148 patients (51.2%). Three patients (0.3%) died as a consequence of surgery. CONCLUSION: Transsphenoidal surgery is an effective and safe treatment for most patients with pituitary adenoma and could be considered the first-choice therapy in all cases except for prolactinomas responsive to dopamine agonists. Other treatment methods, such as radiotherapy, stereotactic radiosurgery, and medical therapy, play an important role in patients not cured by surgery.

Surgical treatment of giant pituitary adenomas: strategies and results in a series of 95 consecutive patients.

OBJECTIVEGiant pituitary adenomas, defined as those measuring at least 4 cm in maximum diameter, are a therapeutic challenge. We report our experience in a large, consecutive series of patients with giant adenomas. METHODSBetween 1990 and 2004, 95 patients with a giant pituitary adenomas underwent surgery at our department. Nonfunctioning pituitary adenoma was the most frequent type (n = 70; 73.7%), whereas hormone-secreting adenomas numbered only 25 (26.3%). The mean age at the time of surgery (±standard error of the mean) was 48.4 ± 1.5 years; there were 66 men (69.5%) and 29 women (20.5%). RESULTSIn total, 111 surgical procedures were performed. Of these, 85 approaches (76.6%) were transsphenoidal and 26 (23.4%) were transcranial. Visual improvement occurred in 59 of the 79 patients with preoperative defect who could be evaluated after surgery (74.7%). Radical tumor excision was obtained in 14 patients (14.7%). Adjuvant medical and radiation therapies led to 74.5% (95% confidence interval, 62.7–86.4%) control of tumor growth at 5 years. This was not different in patients with nonfunctioning pituitary adenomas compared with patients with hormone-secreting tumors. In the subgroup of patients with nonfunctioning pituitary adenomas, radiation therapy had a protective role against tumor growth (P < 0.01). CONCLUSIONMaximal surgical removal of giant adenomas through the transsphenoidal or transcranial approach, or both, aimed to relieve compression of the optic pathway and reduce tumor volume as much as possible, offers the best chances to control the tumor when followed with adjuvant medical and radiation therapies.

Surgical strategies and modern therapeutic options in the treatment of craniopharyngiomas

The optimal treatment of patients with craniopharyngioma remains controversial. In particular, the role of aggressive treatment compared to less aggressive therapeutic options is poorly understood. Radical resection is the therapy of choice at any age, because it is associated with the best outcome in terms of survival. Nevertheless, aggressive behaviour, location, involvement of critical structures, tumour size, calcifications, and patient age may limit the extent of resection. Surgery can also carry significant morbidity in terms of visual, hypothalamic, and endocrinological disturbances. Long term sequelae reduce the quality of life in 50% of long-term survivors, notably obesity and neurobehavioral impairment due to hypthalamic involvement and iatrogenic induced lesions. The quality of life should be considered as a clinically important endpoint in patients, who currently experience good overall survival rates, regardless of the degree of surgical resection. Tendency to recur despite negative postoperative imaging led many authors to advocate a less aggressive surgical treatment followed by radiation therapy. We review the data reported in the literature, especially early outcome after surgical treatment and factors affecting the risk of tumour recurrence, to elucidate the role of attempted radical resection in the treatment of craniopharyngioma and to identify the clinical and morphological characteristics predictive for the best surgical prognosis.

Evaluation of 1p36 markers and clinical outcome in a skull base chordoma study

Chordomas are rare embryogenetic tumors, arising from remnants of the notochord, characterized by local invasiveness and variable tendency for recurrence. No molecular markers are currently used in a clinical setting to distinguish chordomas with an indolent or an aggressive pattern. Among the genetic lesions observed in this tumor, one of the most commonly detected is 1p loss. In a previous study we observed 1p36 loss of heterozygosity (LOH) in 85% of the analyzed chordomas. We studied a group of 16 homogeneously treated skull base chordomas (SBCs), reporting 1p36 LOH in 75% of them and determining the expression pattern of eight apoptotic genes mapped at 1p36. No tumors shared a common expression profile with nucleus pulposus, which is considered the only adult normal tissue deriving from notochord. In particular, tumor necrosis factor receptor superfamily genes TNFRSF8, TNFRSF9, and TNFRSF14 were differently expressed compared with control in a higher percentage of tumors (40%-53%) than were the remaining analyzed genes, suggesting that the deregulation of these three genes might have a role in chordoma tumorigenesis. The presence/absence of LOH and the expression/nonexpression of each apoptotic gene were studied in a survival analysis. Our results suggest that the lack of 1p36 LOH or the presence of TNFRSF8 expression might be associated with a better prognosis in patients with SBCs.

Reconstruction techniques in skull base surgery.

One of the major challenges of cranial base surgery is reconstruction of basal dural defects. Ineffective reconstruction may result in potentially life-threatening complications such as cerebrospinal fluid leak, meningitis, and tension pneumocephalus. Goals of reconstructive procedures are to repair the dural defect and to separate intracranial contents from bacteria-laden secretion of the mouth, nose, and sinus. Different reconstructive techniques have been reported. Multiple factors may influence the surgical choice of reconstructive technique and its outcome. Regional pedicled flap and vascular free flaps represent the best reconstructive options because vascularized tissues promote fast and complete healing. A variety of endoscopic pedicled mucosal flaps within the nasal cavity have also been described. The different reconstruction techniques are described and discussed in terms of indications, advantages, and drawbacks.

The pterygopalatine fossa: an anatomic report.

The pterygopalatine fossa (PPF) is a small anatomic region of particular interest in cranial base surgery. Infectious diseases and malignancy may spread through the PPF to contiguous areas as a result of the low resistance offered by the numerous foramina and fissures that surrounds the fossa. We present an anatomic report on the PPF. Twelve sides of six fixed cadaveric heads were dissected through a LeFort I maxillary osteotomy with transantral exposure of the neurovascular content of the PPF. Arterial vascular patterns of the maxillary artery were observed. The pterygopalatine fossa is a deeply located small anatomic region with a rich neurovascular content. The third portion of the maxillary artery in the PPF may demonstrate a variable vascular morphology. A correct understanding and knowledge of the anatomic structures lodged into the PPF, as well as their relationships and functions, remain crucial to minimizing postsurgical morbidity and intraoperative complications.

Skull base chordomas: clinical outcome in a consecutive series of 45 patients with long-term follow-up and evaluation of clinical and biological prognostic factors

OBJECTIVE Skull base chordomas (SBCs) are rare dysembryogenetic invasive tumors with a variable tendency for recurrence. According to previous studies, the recurrence rate seems to be affected by both clinical variables and tumor biological features. The authors present the results of treatment of SBCs in a large series of patients and investigate the role of 1p36 chromosomal region loss of heterozygosity (LOH) as a prognostic factor. METHODS Between 1990 and 2011, 45 patients were treated for SBCs. The mean follow-up was 76 months (range 1-240 months). An LOH analysis was performed in 27 cases. Survival analysis was performed to determine clinical and biological parameters correlating with clinical outcome. RESULTS The 5- and 10-year overall survival rates were 67% and 57%, respectively. Five- and 10-year progression-free survival rates were 58% and 44%, respectively. Multivariate analysis showed that extent of resection, adjuvant radiation therapy, and absence of rhinopharynx invasion were positive independent predictors of overall survival. The latter 2 variables and a younger patient age were positive independent predictors of progression-free survival. Twenty-one patients showed 1p36 LOH. All events of recurrence and death clustered in the group of patients with 1p36 LOH; however, this biological marker was not statistically significant on multivariate analysis. CONCLUSIONS Resection is the treatment of choice in primary and recurrent SBC. Patient age, rhinopharynx invasion at diagnosis, extent of tumor removal, and postoperative radiation therapy influence SBC prognosis. Genetic analysis, even while showing interesting results, did not reveal 1p36 LOH as an independent predictor of clinical outcome.

The role of CXCR4 in highly malignant human gliomas biology: current knowledge and future directions.

Given the extensive histomorphological heterogeneity of high‐grade gliomas, in terms of extent of invasiveness, angiogenesis, and necrosis and the poor prognosis for patients despite the advancements made in therapeutic management. The identification of genes associated with these phenotypes will permit a better definition of glioma heterogeneity, which may ultimately lead to better treatment strategies. CXCR4, a cell surface chemokine receptor, is implicated in the growth, invasion, angiogenesis and metastasis in a wide range of malignant tumors, including gliomas. It is overexpressed in glioma cells according to tumor grade and in glioma tumor initiating cells. There have been various reports suggesting that CXCR4 is required for tumor proliferation, invasion, angiogenesis, and modulation of the immune response. It may also serve as a prognostic factor in characterizing subsets of glioblastoma multiforme, as patients with CXCR4‐positive gliomas seem to have poorer prognosis after surgery. Aim of this review was to analyze the current literature on biological effects of CXCR4 activity and its role in glioma pathogenesis. A better understanding of CXCR4 pathway in glioma will lead to further investigation of CXCR4 as a novel putative therapeutic target. GLIA 2014;62:1015–1023

Current therapeutic options and novel molecular markers in skull base chordomas.

Chordomas are extremely rare tumours. They arise in the spheno-occipital region in 35% of cases. Chordomas usually present benign histopathological features but often exhibit a malignant clinical behaviour. Radical surgical removal and high-dose radiation therapy seem to be effective in tumour control and to improve survival rate. Despite the advancements in microsurgical techniques and the development of radiation therapies, clival chordomas still represent a challenge. Nevertheless it appears that chordomas that have been resected to the same extent and that received post-operative radiotherapy might exhibit different rates of regrowth. This result supports the hypothesis that the recurrence rate of chordomas might be dependent on biological variables other than the extent of resection and the post-operative radiotherapy. Genetic and molecular studies on oncogenesis of chordomas are still limited, but they represent the basis for the development of molecular targeted therapies. We present a review of the current knowledge about skull base chordomas biology, therapeutic options and related clinical outcome.

Surgical treatment of orbital cavernomas: clinical and functional outcome in a series of 20 patients

PurposeThe aim of this study is to assess the efficacy and safety of surgical treatment of orbital cavernomas in terms of clinical and functional results.MethodsTwenty consecutive patients underwent surgical removal of a unilateral orbital cavernoma between 1999 and 2009. Indications for surgical treatment were: visual impairment, diplopia due to ocular movement impairment, progressive and disfiguring unilateral proptosis, severe retroorbital pain clearly related to the orbital cavernoma. We used a topographic classification of the lesions within the orbit. The orbit has been divided into an anterior and a posterior compartment on the axial plane and into three sectors on the coronal plane. The proptosis was quantified on MRI scans.ResultsThe location of the cavernoma determined the choice of the surgical approach. We performed eight lateral orbitotomies and 12 fronto-orbito-zygomatic approaches. All the tumors were completely removed as assessed at follow-up MRI. We did not record any intraoperative or major postoperative complication requiring a reoperation. The postoperative visual acuity improved in four of five patients with visual impairment, it worsened in the other case. Proptosis improved in all the patients. Diplopia improved in four patients, and did not recover in another case.ConclusionSurgical treatment of symptomatic orbital cavernomas is safe and effective. Tumor location dictates the choice of surgical approach. Visual function and cosmetic result are the main parameters to evaluate the clinical outcome. Surgical approach and dissection technique are crucial in determining the visual outcome.