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Paolo Cappabianca

Publications and source records attributed to Paolo Cappabianca.

At least 19 recordsLinked to original sources
PubMed2009

HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas.

The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.

Adenoma↗
PubMed2007

Recurrences of meningiomas: predictive value of pathological features and hormonal and growth factors.

OBJECTIVE: Recurrence of apparently completely resected benign meningiomas is a rather frequent event, the mechanisms of which are still unclear. The aim of this study is to define the pathological features, proliferation indexes, growth factors and hormone receptor expression in predicting the meningioma recurrence. METHODS: Two groups of 50 completely resected benign WHO I meningiomas, with and without recurrence respectively, have been reviewed. Tumor location, consistency, vascularity, and histological types have been considered. Immunohistological studies include mitotic index (MI), Ki-67 LI, estrogen and progesterone receptors (ER and PR), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), and Bcl-2. All these factors have been correlated with the recurrence. RESULTS: The tumor recurrence was not correlated with the patient age, tumor location, consistency, vascularity and histology. There was not difference in the histological pattern between local and diffuse recurrences. M.I. and Ki-67 LI were significantly correlated with the recurrence (P<0.0001). PR negativity had a strong predictive value of recurrence (P<0.0001), whereas the ER status was not relevant. VEGF and EGF-R were not correlated with the recurrence of meningiomas, whereas the Bcl-2 protein positivity showed a tendency to the significativity (P=0.0294). The negative association between Bcl-2 and PR is an interesting finding of our study. CONCLUSIONS: Higher MI and Ki-67 LI and PR negativity are predictive factors of recurrence of benign (WHO I) completely resected meningiomas, particularly when Bcl-2 positivity is associated.

Age Factors↗
PubMed2007

Extended endoscopic endonasal transsphenoidal approach for the removal of suprasellar tumors: Part 2.

OBJECTIVE: The widespread use of the endoscope in transsphenoidal pituitary surgery has recently contributed to the extension of the approach beyond the tuberculum sellae and planum sphenoidale for the management of lesions located in the suprasellar area, either with an endoscope-assisted or purely endoscopic technique. Based on our previous experience with more than 450 standard endoscopic transsphenoidal operations, we have retrospectively evaluated the effectiveness of the extended endoscopic endonasal transsphenoidal approach in the management of lesions mainly located in the suprasellar area. METHODS: Between January 2004 and December 2005, 20 consecutive patients underwent extended endoscopic endonasal transsphenoidal surgery for a total of 21 procedures. The series consisted of seven pituitary adenomas, seven craniopharyngiomas, three suprasellar Rathke's cleft cysts, two tuberculum sellae meningiomas, and one pilocytic astrocytoma of the chiasm. RESULTS: Tumor removal, as assessed by postoperative magnetic resonance imaging, revealed complete removal of the lesion in four out of seven pituitary adenomas, five out of seven craniopharyngiomas, three out of three Rathke's cleft cysts, and two out of two tuberculum sellae meningiomas. One patient (5%) with craniopharyngioma had a postoperative cerebrospinal fluid leak that required reoperation. The same patient experienced a sphenoid mycosis, which was treated with medical therapy. Some specific conditions associated with the anatomy of the surgical route, as well as to the morphology of the lesion, have resulted to condition the feasibility of the approach. CONCLUSION: Small and medium sized suprasellar lesions located in the midline, with or without a limited parasellar extension and without involvement of vascular structures, seem amenable to be resected through such extended endoscopic transsphenoidal approach. Improvements in closure techniques and the use of new materials and surgical glues seem to significantly reduce the postoperative cerebrospinal fluid leak rate and meningitis.

Adult↗
PubMed2006

Lhermitte-Duclos disease.

A 46-year-old female patient with previously recognized Graves' ophthalmopathy, underwent total thyroidectomy. After thyroid surgery exophthalmos worsened and signs unsteadiness of gait appeared. Magnetic resonance imaging showed a lesion in the basal portion of the left cerebellar hemisphere. Therefore, the patient underwent surgery. Pathological examination revealed dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease).

Cerebellar Neoplasms↗
PubMed2006

Back to the Egyptians: neurosurgery via the nose. A five-thousand year history and the recent contribution of the endoscope.

The possibility of removing the brain through the nose without disfiguring the face was already known to the ancient Egyptians, who were experts in using this approach in the mummification process. A similar route through the nose and the sphenoid bone has been developed in the last century as a surgical procedure for the treatment of tumors of the pituitary region, which makes the more invasive craniotomy unnecessary in most cases. This has resulted in a significant decrease of the overall mortality and morbidity rates and has led to the great popularity of such minimally invasive surgery both for patients and doctors. The recent advent of the endoscope in this specific field and the development of further possibilities and instrumentation has contributed to a new renaissance of this old treatment modality.

Egypt, Ancient↗
PubMed2006

Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors.

OBJECT: The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors. METHODS: Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor-b [TGFb], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases). The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFb expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFb, PDGF, and tenascin in more aggressive cavernomas. CONCLUSIONS: The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.

Adolescent↗
PubMed2006

Surgery as art.

Explore the source record for details and available documents.

Art↗
PubMed2006

Use of equine collagen foil as dura mater substitute in endoscopic endonasal transsphenoidal surgery.

OBJECTIVE: This study describes the use of a novel collagen-based dural substitute in endoscopic endonasal transsphenoidal surgery. METHODS: Operative records were reviewed for a 12-month period for all patients who underwent surgery by means of an endoscopic endonasal transsphenoidal approach since we began using TissuDura (Baxter, Vienna, Austria) collagen-only dural substitute in January 2004. RESULTS: During the 12-month period evaluated, we performed an endoscopic endonasal transsphenoidal operation for a variety of pituitary lesions on 72 consecutive patients. Among these, 15 patients (20.8%) required the implant of the collagen foil. Nine patients (60%) presented an intraoperative CSF leak (3 small weeping of CSF and 6 larger leaks); in these cases, the TissuDura was used against the arachnoid membrane, followed by the other materials used for the repair. In 7 other subjects without any evidence of CSF escape, the collagen foil was used to protect and enforce the arachnoidal membrane descent into the sellar cavity to prevent its possible postoperative rupture and consequent CSF leak. Fibrin glue was used in all cases. A postoperative CSF leak with meningitis occurred in only 1 (6.7%) of the 15 subjects. The patient required a reoperation for CSF fistula repair and intravenous antibiotics. CONCLUSIONS: Even if based on a relatively small patient series, our experience demonstrated that the use of TissuDura in transsphenoidal surgery is safe and biocompatible, as compared with other dural substitutes.

Animals↗
PubMed2006

Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.

In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Adenoma↗
PubMed2006

Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly.

BACKGROUND: This analytical, retrospective study was designed to select cut-off thresholds of mean GH levels during a diurnal profile and nadir GH levels after oral glucose tolerance test (OGTT) according to age to diagnose surgical remission of acromegaly. METHODS: One hundred forty-one patients (76 women, aged 44 +/- 15 years and 65 men, aged 43 +/- 13 years) were included in this study. For the purpose of this study, remission was based on insulin-like growth factor-I (IGF-I) levels in the normal range for age. Diagnostic accuracy was analysed by receiving-operator characteristics (ROC) curves in the entire series, and in young (20-40 years), middle-aged (41-60 years) and older patients (> 60 years), separately. RESULTS: Sixty patients (42.6%) had normal IGF-I levels after surgery. In the entire series, in young and in middle-aged patients, the ROC analysis showed that optimum cut-off for mean GH levels was 2.3 microg/l (diagnostic accuracy range, 94-97%) whereas that for nadir GH after OGTT were, respectively, 0.85, 0.9 and 0.8 microg/l (diagnostic accuracy range, 90-95%). In the older patients, the optimum cut-off selected for mean GH levels was 1.4 microg/l and that for nadir GH after OGTT was 0.5 microg/l (diagnostic accuracy, 100% for both). The comparative analysis of the ROC curves did not show any significant difference between mean GH and nadir GH after OGTT (P = 0.21). CONCLUSIONS: The criteria currently accepted for diagnosing post-surgical remission of acromegaly have high diagnostic accuracy only in the patients aged below 60 years. In older patients, lower cut-offs (i.e. = 1.4 microg/l for fasting GH and = 0.5 microg/l for nadir GH after OGTT) predict normal IGF-I levels. Mean GH levels during a diurnal profile have similar diagnostic accuracy of nadir GH levels after OGTT. This suggests that OGTT is not necessary to establish surgical cure.

Acromegaly↗
PubMed2006

The endoscopic endonasal approach to the lateral recess of the sphenoid sinus via the pterygopalatine fossa: comparison of endoscopic and radiological landmarks.

OBJECTIVE: The endoscopic endonasal approach offers the opportunity to reach the pterygopalatine fossa, the lateral recess of the sphenoid sinus, and other areas of the cranial base through a minimally invasive approach. This study compares the anatomy of these areas when observed through an endoscopic endonasal view with the anatomy of the same regions as they appear in computed tomographic scans. The aim was to identify and correlate the corresponding anatomic structures, providing the surgeons with anatomic landmarks to guide them when operating in these areas through an endoscopic endonasal approach. METHODS: An anatomic dissection of six fixed cadaver heads was performed by an endoscopic endonasal approach. A step-by-step comparison of endoscopic and radiological images was made to identify the landmarks of the surgical field. RESULTS: The step-by-step comparison of endoscopic and radiological images acquired during the endoscopic endonasal approach to the lateral recess of the sphenoid sinus via the pterygopalatine fossa allowed the identification of all the relevant anatomic landmarks of the procedure. CONCLUSION: The endoscopic endonasal approach via the pterygopalatine fossa offers direct, minimally invasive access to the lateral recess of the sphenoid sinus, which can be monitored in each phase through consistent radiological imagery.

Cadaver↗
PubMed2005

Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly.

CONTEXT: Surgery is a cornerstone in the treatment of acromegaly, but its efficacy in large, invasive tumors is scant. OBJECTIVE: The objective of this study was to investigate whether partial surgical removal of GH-secreting pituitary tumors enhances the response rate to somatostatin analogs (SSA; sc octreotide, slow-release octreotide, and lanreotide). DESIGN: This was a multicenter, open, retrospective study. SETTING: The study was performed at university hospitals. SUBJECTS AND METHODS: Eighty-six patients (42 women and 44 men; age, 42 +/- 14 yr) with acromegaly were studied. INTERVENTIONS: Patients underwent two courses of octreotide, lanreotide, or slow-release octreotide treatments before and after surgery of at least 6 months. MAIN OUTCOME MEASURE: The main outcome measure was normal IGF-I levels for age. RESULTS: Presurgical SSA treatment significantly decreased GH and IGF-I levels in all patients. GH levels were less than 2.5 microg/liter in 12 patients (14%); IGF-I levels normalized in nine (10%). After surgery, GH and IGF-I levels further decreased in all patients; tumor removal was greater than 75% in 50 (58%), 50.1-75% in 21 (24%), 25.1-50% in 10 (12%), and less than 25% in five patients (6%). Preoperatively, pituitary function was impaired in 12 patients (14%). Postsurgical SSA treatment lowered GH levels to less than 2.5 microg/liter in 49 (56%) and normalized IGF-I levels in 48 patients (55%). The success rate was significantly increased compared with that before surgery (P < 0.0001). GH (r = -0.48; P < 0.0001) and IGF-I levels (r = -0.38; P = 0.0003) after postsurgery SSA treatment correlated with the amount of tumor surgically removed. After surgery, pituitary function was impaired in 28 patients (32.6%) and was improved in 12 patients (13.9%). The cumulative prevalence of pituitary deficiency did not change during the study (normal function from 40 to 42%; deficiency from 60 to 58%). CONCLUSIONS: Surgical tumor removal (>75%) enhances the response to SSAs without impairing pituitary function. Our data indicate that surgical debulking has a significant place in the treatment algorithm of acromegaly.

Acromegaly↗
PubMed2005

Endoscopic endonasal surgery of the midline skull base: anatomical study and clinical considerations.

OBJECT: The midline skull base is an anatomical area that extends from the anterior limit of the cranial fossa down to the anterior border of the foramen magnum. Resection of lesions involving this area requires a variety of innovative skull base approaches. These include anterior, anterolateral, and posterolateral routes, performed either alone or in combination, and resection via these routes often requires extensive neurovascular manipulation. The goals in this study were to define the application of the endoscopic endonasal approach and to become more familiar with the views and skills associated with the technique by using cadaveric specimens. METHODS: To assess the feasibility of the endonasal route for the surgical management of lesions in the midline skull base, five fresh cadaver heads injected with colored latex were dissected using a modified endoscopic endonasal approach. Full access to the skull base and the cisternal space around it is possible with this route. From the crista galli to the spinomedullary junction, with incision of the dura mater, a complete visualization of the carotid and vertebrobasilar arterial systems and of all 12 of the cranial nerves is obtainable. CONCLUSIONS: The major potential advantage of the endoscopic endonasal approach to the skull base is that it provides a direct anatomical route to the lesion without traversing any major neurovascular structures, obviating brain retraction. Many tumors grow in a medial-to-lateral direction, displacing structures laterally as they expand, creating natural corridors for their resection via an anteromedial approach. Potential disadvantages of this procedure include the relatively restricted working space and the danger of an inadequate dural repair with cerebrospinal fluid (CSF) leakage and potential for meningitis resulting. These approaches often require a large opening of the dura mater over the tuberculum sellae and posterior planum sphenoidale, or retroclival space. In addition, they typically involve large intraoperative CSF leaks, which necessitate precise and effective dural closure.

Cadaver↗
PubMed2005

Extended endoscopic endonasal approach to the pterygopalatine fossa: anatomical study and clinical considerations.

OBJECT: The pterygopalatine fossa is an area located deep in the skull base. The microsurgical transmaxillary-transantral route is usually chosen to remove lesions in this region. The increasing use of the endoscope in sinonasal functional surgery has more recently led to the advent of the endoscope for the treatment of tumors located in the pterygopalatine fossa as well. METHODS: An anatomical dissection of three fresh cadaveric heads (six pterygopalatine fossas) and three dried skull base specimens was performed to evaluate the feasibility of the approach and to illustrate the surgical landmarks that are useful for operations in this complex region. The endoscopic endonasal approach allows a wide exposure of the pterygopalatine fossa. Furthermore, with the same access (that is, through the nostril) it is possible to expose regions contiguous with the pterygopalatine fossa, either to visualize more surgical landmarks or to accomplish a better lesion removal. CONCLUSIONS: In this anatomical study the endoscopic endonasal approach to the pterygopalatine fossa has been found to be a safe approach for the removal of lesions in this region. The approach could be proposed as an alternative to the standard microsurgical transmaxillary-transantral route.

Cranial Fossa, Anterior↗
PubMed2005

Effect of gender and gonadal status on the long-term response to somatostatin analogue treatment in acromegaly.

UNLABELLED: :GH and IGF-I secretion is related to gender and age. OBJECTIVE: To evaluate the impact of gender and gonadal status on the long-term sensitivity to the somatostatin analogues depot octreotide long-acting release (OCT-LAR) and lanreotide (LAN). PATIENTS: Seventy-three patients with active acromegaly (37 women, median age 34 years; 36 men, median age 38 years) who had not previously been treated with somatostatin analogues were studied: 24 women and 23 men were newly diagnosed; 22 men (61.1%) and 17 women (45.9%) had hypogonadism (P=0.28). Exclusion criteria were age >45 years, follow-up less than 12 months, mixed GH/PRL-secreting adenomas. Study design Observational, analytical, retrospective. Outcome measures (1) Disease control measured as serum GH< 2.5 microg/l and IGF-I normal for age and gender; (2) reduction in tumour volume graded as absent (< 25%), mild (25-50%) and notable (>50%). Results Basal GH, but not IGF-I, levels were higher in women than in men both in the entire series and in 'de novo' patients (97.8+/- 42.2 vs. 71.1+/- 32.6 microg/l, P=0.021). After 12 and 24 months of treatment, respectively, disease control was achieved similarly in men (57.1 and 86.7%) and women (48.6 and 86.7%). Hypogonadal men had longer disease duration than eugonadal men (P=0.022), without any difference in the other parameters. No difference was found between eugonadal and hypogonadal women. Eugonadal men had a smaller tumour volume at baseline than eugonadal women (1396+/- 794 vs. 2896+/- 2871 mm(3), P=0.025). In men undergoing testosterone replacement and withdrawal, there was no change in GH and IGF-I levels after 12 and 24 months of treatment with either LAR or LAN. In the seven women receiving oestro-progestinic replacement, after 24 months of LAR or LAN treatment GH levels were higher during replacement than at withdrawal and IGF-I levels were lower during replacement than withdrawal. Tumour volume decreased significantly in both women and men without any difference between them: the percentage tumour shrinkage in men and women was similar either after 12 (34.4+/-24.4 vs. 40.7+/-22.5%, P=0.38) or 24 months of treatment (58.5+/- 17.4 vs. 56.1+/- 23.6%, P=0.75). Similarly, there was no difference in tumour volume between hypogonadal and eugonadal women and men. CONCLUSIONS: The results of this study demonstrate that long-term responsiveness to OCT-LAR is similar in women and men. Care should be taken in women with acromegaly and hypogonadism treated with somatostatin analogues and oral oestro-progestinic as in this case GH levels are higher while IGF-I levels are lower than after the somatostatin analogues alone.

Acromegaly↗
PubMed2005

Endoscopic transnasal approach to the cavernous sinus versus transcranial route: anatomic study.

OBJECTIVE: The aim of the present study was to compare the anatomy of the cavernous sinus via an endoscopic transnasal route with the anatomy of the same region explored by the transcranial route. The purpose was to identify and correlate the corresponding anatomic landmarks both through the endoscopic transnasal transsphenoidal and the microscopic transcranial views. METHODS: Five fresh injected heads (10 specimens) were dissected by the endoscopic transnasal and microsurgical transcranial approaches. A comparison of different microsurgical corridors of the cavernous sinus with the corresponding endoscopic transnasal ones was performed. RESULTS: Through the endoscopic transnasal approach, it is possible to explore only some of the parasellar and middle cranial fossa subregions. Because of the complex multilevel architecture of the cavernous sinus, there is not always a correspondence between the surgical corridors bounded through the transcranial route and those exposed through the endoscopic transnasal approach. Nevertheless, some surgical corridors specific to the endoscopic transnasal route are evident: a C-shaped corridor is identifiable medial to the "intracavernous" internal carotid artery, whereas a wider triangular area is delineable lateral to the internal carotid artery; inside the latter, three more surgical corridors (a superior triangular space, a superior quadrangular space, and an inferior quadrangular space) can be described. CONCLUSION: Different surgical corridors can be defined during the endoscopic transnasal approach to the anteroinferior portion of the cavernous sinus, as already established for the transcranial route as well. Knowledge of these could be useful in decreasing morbidity and mortality during surgery in this region, these approaches being reserved to experienced transsphenoidal surgeons only.

Cadaver↗