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Biomedical subjects

M Giovanelli

Publications and source records attributed to M Giovanelli.

At least 19 recordsLinked to original sources

Assessment of cure and recurrence after pituitary surgery for Cushing's disease.

BACKGROUND: The treatment of choice in Cushing's disease is transsphenoidal adenomectomy with a recurrence rate ranging 9-23%. We investigated whether abnormal hormonal responses may predict the relapse in "operated" patients followed-up for a long period. METHOD: Sixty-eight surgically treated patients with Cushing's disease were followed-up for 12-252 months. Forty-eight patients underwent selective adenomectomy, 17 enlarged adenomectomy and 3 underwent total hypophysectomy. After surgery ACTH and cortisol levels were measured after stimulatory (desmopressin and CRH) and inhibitory tests (dexamethasone and loperamide). FINDINGS: After operation 46 patients were cured (group A), 15 patients only normalized cortisol levels (group B), 7 patients were surgical failures. During the follow-up, a disease-free condition was maintained in 48 of 61 cases (79%), while a recurrence occurred in 13 patients (21%, 5 of group A and 8 of group B). In 5/13 patients who relapsed an absent inhibition after dexamethasone and an exaggerated response to CRH test preceded the recurrence. In 5 other patients the relapse was suspected by loperamide test. In the 3 remaining cases, positive responses to desmopressin preceded the recurrence. In 7/13 patients who relapsed the pituitary tumour was visualized by MRI/CT imaging. INTERPRETATION: During the follow-up a careful assessment of ACTH dynamics is needed. Although no single test can reliably predict the late outcome, individual patients at risk for relapse may be identified by abnormal responses to desmopressin, CRH and loperamide tests; particularly, the persistent responsiveness to desmopressin may be a criterion of risk for recurrence in patients who only normalized cortisol levels after surgery.

Adenoma↗

Desmopressin stimulation test before and after pituitary surgery in patients with Cushing's disease.

OBJECTIVE: The desmopressin test has been proposed as a useful tool for the differential diagnosis of Cushing's disease. The aim of our study was to investigate, in a large series of patients with Cushing's disease, the incidence of a positive ACTH and cortisol response to desmopressin. Moreover, we repeated the test soon after surgery to verify its usefulness in the assessment of early and late surgical results. PATIENTS AND METHODS: One hundred and seven consecutive patients with Cushing's disease, 89 female and 18 male patients, with a mean age of 37.2 +/- 1.3 years, were studied. All patients, except three, repeated the test 5-6 days after surgery. Desmopressin (10 microg) was injected i.v. and blood samples were drawn 15, 30, 45 and 60 minutes thereafter. Plasma ACTH and serum cortisol were measured in duplicate by commercially available immunoassays. A positive response to desmopressin was considered to be a plasma ACTH and serum cortisol increment of at least 30% and 20% above baseline, respectively. RESULTS: Mean basal plasma ACTH level was 17.3 +/- 1.7 pmol/l and rose to a peak level of 42.7 +/- 4.9 pmol/l at 15 minutes Mean basal serum cortisol level was 574 +/- 19 nmol/l and rose to a peak level of 814 +/- 28 nmol/l at 45 minutes. ACTH and cortisol incremental changes were inversely correlated with their respective basal levels. Ninety patients (84.1%) had an ACTH and 84 patients (78.5%) had a cortisol response to desmopressin. Several clinical and demographic characteristics were not significantly different among desmopressin responders and non responders, except that basal ACTH and cortisol levels were significantly higher in desmopressin non responders (27.2 +/- 8.3 pmol/l, 781 +/- 86 nmol/l) than in desmopressin responders (15.4 +/- 1.2 pmol/l, 535 +/- 14 nmol/l). Disappearance of the ACTH and cortisol response to desmopressin after surgery occurred in 50 of 87 (57%) ACTH responders and in 57 of 81 (70.4%) cortisol responders, respectively. However, concordance between the desmopressin test and surgical outcome was not complete. Indeed, 18 patients considered in remission still showed an ACTH increase after desmopressin and, on the contrary, four patients with disappearance of the ACTH response had persistence of hypercortisolism. During follow-up monitoring, three patients, who had persistence of the ACTH response to desmopressin, relapsed 24, 38 and 54 months after surgery. CONCLUSIONS: Desmopressin administration elicits a significant rise in ACTH and cortisol levels in the majority but not all patients with Cushing's disease. There is a good, but not complete, concordance between the response to the desmopressin test and the surgical outcome. Our preliminary data show that persistence of the ACTH response to desmopressin in the early postoperative period might be associated with a higher risk of late relapse.

Adolescent↗

A comparative evaluation of effectiveness of medical and surgical therapy in patients with macroprolactinoma.

BACKGROUND: The surgical success rate in macroprolactinomas is quite low, while medical treatment is more effective in reducing PRL levels and tumour mass. In this study the effectiveness of surgical, medical and radiant approaches on clinical symptoms, PRL levels and tumour size were compared in a large series of patients with macroprolactinomas. METHODS: One hundred and thirty-two patients (63 males and 69 females) were followed-up. Eighty-three patients were operated by trans-sphenoidal (TSS) approach: 18 underwent only TSS, 10 were operated and then irradiated; 30 patients underwent TSS and dopamine agonists, 25 were treated by TSS, radiotherapy and dopamine agonists. One hundred and four patients were treated by medical therapy: 49 patients were only administered dopamine agonists and 55 were given dopamine agonists after unsuccessful surgery and/or radiotherapy. RESULTS: In 83 patients serum PRL levels decreased from 1873+/-319.9 ng/ml to 831.6+/-297.8 ng/ml after trans-sphenoidal surgery: a significant PRL reduction was obtained in 18 cases (22%) and a full PRL normalization was found in 15 patients (18%). The pituitary adenoma was completely removed in the 15 cases, in whom serum PRL normalized. Sexual function was restored in 57 percent; of women and in 29 percent; of men. In contrast, dopaminergic drugs normalized PRL levels (from 1590.5+/-232.7 to 19.2+/-4.8 ng/ml) in 93/104 patients (89 percent;). Sexual function was restored in 74 percent; of women and in 75 percent; of men. Radiotherapy, performed after unsuccessful TSS, was ineffective in normalizing PRL levels. CONCLUSIONS: Medical therapy should be considered the first choice treatment in macroprolactinomas, while the surgical approach is recommended when neurological compressive symptoms are present and in patients resistant or intolerant to dopamine agonists. Radiotherapy may be indicated only in the patients in whom medical and surgical therapy have not been successful.

Adult↗

Chondrosarcoma of the thoracic spine: total en bloc sagittal resection. A case report.

Chondrosarcomas located in the spine are uncommon tumors and are challenging to manage. A case of a 65-year-old man with a T3-T4 spine chondrosarcoma is reported. The onset of symptoms consisted in progressive dorsal pain with sometimes a girdle-like radiation and, successively, in dysaesthesia and paresthesia from the lower limbs to the thoracic region. After preoperative oncologic and surgical planning the patient underwent a total en bloc resection of the mass. No postoperative adjunctive neurological deficits were recorded. An adjuvant radiation therapy with a dose of 5.500 centigrays (cGy) over four weeks was performed. At one year follow-up the patient is alive with no signs of recurrence on computed tomographic scans and magnetic resonance imaging. We discuss this case with particular emphasis on the preoperative planning, the surgical procedure and related prognosis.

Aged↗

Introduction of GDC embolization in the clinical practice as treatment synergical to surgery: impact on overall outcome of patients with subarachnoid hemorrhage.

The GDC endovascular approach represent an effective alternative to surgery for treatment of intracranial aneurysms. Anyway no data are available about the impact of endovascular embolization with GDC on overall outcome of patients with subarachnoid hemorrhage. We analyse retrospectively a series of 234 patients admitted for ruptured intracranial aneurysm. Results were then compared with results of three surgical series from the literature. The 95.7% of patients underwent aneurysm treatment; 56.4% of patients were classified as good recovery, 12.8% presented moderate disability, 10.3% were severely disabled, 3% were in persistent vegetative state and 17.5% were dead. Patients older than 60 years accounted for 37% of all cases and good outcome in this group accounted for 54.7%. Good results were obtained in 90.1%, 61.7% and 22.8% of patients with Hunt-Hess grade I-II, III and IV-V respectively. Finally good outcome was observed in 82.8% of patients with aneurysms of the posterior circulation. Introduction of GDC embolization in clinical practice contributed to the extension of indication for aneurysm treatment leading to a reduction of overall mortality. GDC utilisation does not affect the overall percentage of patients with good outcome reflecting an increase of severely disabled patients. Endovascular treatment seems an effective theraputic choice in selected grade I-II patients. Results in grade III patients suggest that surgery may be advantageous because of washing and decompression of the basal cisterns while results in grade IV and V patients are unsatisfactory. GDC embolization clearly improves the prognosis of patients with posterior circulation aneurysms and probably is an advantageous theraputic choice in elderly patients.

Adolescent↗

Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors : comparison between micro- and macroadenomas.

We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing's disease subdivided according to tumor size. Fifty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 +/- 1.5 years), were studied. Thirty-six patients had a microadenoma and the remaining 15 a macroadenoma. Immunohistochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. Ki-67 labeling index and apoptosis were counted on separate slides in at least 1000 evaluable cells. Patients with a macroadenoma had a significantly higher value of Ki-67 index (9.3 +/- 2.7%) than patients with microadenoma (2.8 +/- 0.5%; P < 0.002), whereas the apoptotic index was not significantly different in the two groups (1.7 +/- 0.8% in macroadenomas versus 0.8 +/- 0.3% in microadenomas). Our study shows that ACTH-secreting macroadenomas are characterized by a higher cell growth fraction than microadenomas, whereas the cell loss fraction is not different. A high proliferation rate seems to play a major role in determining the progression from small to large pituitary tumors in Cushing's disease.

Adenoma↗

Acromegaly associated with a granular cell tumor of the neurohypophysis: a clinical and histological study. Case report.

Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma, and hypersecretion of GH-releasing hormone (GHRH) from a hypothalamic or neuroendocrine tumor accounts for other cases. The authors report on the unusual association of acromegaly with a granular cell tumor of the neurohypophysis. A 42-year-old woman with a 10-year history of acral enlargement, headache, and menstrual abnormalities was referred to our department for a suspected GH-secreting pituitary adenoma. The patient's basal GH levels were mildly elevated at 4.8 microg/L, were not suppressed in response to an oral glucose tolerance test, and increased paradoxically after administration of thyrotropin-releasing hormone. The patient's insulin-like growth factor-1 (IGF-1) level was elevated at 462 microg/L, whereas a magnetic resonance image of the sella turcica revealed an intra- and suprasellar lesion that was compatible with a diagnosis of pituitary adenoma. A transsphenoidal approach to remove the lesion, which was mainly suprasellar, was successful during a second operative attempt, resulting in the clinical and biochemical regression of the patient's acromegaly. Four months postoperatively, the patient's basal GH level was 0.9 microg/L and her IGF-1 level was 140 microg/L. Histological analysis of the operative specimen demonstrated a granular cell tumor of the neurohypophysis, which when stained proved negative for pituitary hormones and GHRH. This case represents the first reported association between a granular cell tumor of the neurohypophysis and acromegaly. Granular cell tumor of the neurohypophysis could be added to the restricted list of neoplastic causes of acromegaly secondary to hypersecretion of a GH-releasing substance.

Acromegaly↗

Glial cyst of the pineal gland: case report and considerations about surgical management.

Symptomatic glial cyst of the pineal gland are rare lesions. Origin, natural history and factors leading to cyst enlargement are not completely clear; thus management remain uncertain in some cases. We report a case of symptomatic glial cyst and analyze the implication for surgery. Surgical management is indicated in patients presenting hydrocephalus, mass effect or symptoms related to mesencephalic dysfunction. The infratentorial supracerebellar approach represent the first choice for this condition allowing easy orientation with wide exposure of the tumor and good visibility of deep venous systems that may be preserved. Size of the tumor is a key element in evaluation of the treatment and the appropriate course for asymptomatic cyst less than 1 cm in size consist of conservative management. Periodic follow up is always indicated.

Adult↗

Fatal carotid dissection after blunt head trauma.

Occurrence of internal carotid artery injuries associated with skull base fracture has been reported. A. report a case of fatal intracranial carotid dissection related to petrous fracture involving the carotid canal. Identification of carotid lesions may be difficult and generally related to appearance of unexpected neurological deficit. Skull base fractures may be considered an indirect sign for detection of vascular injury. Patterns of the fracture are of paramount importance; routine CT scan may fail to detect basilar fractures and high definition fine-cut CT scan should be executed to carefully identify and evaluate fractures. Temporal and sphenoid bone fractures are common in head trauma and involvement of the course of the carotid artery is frequent. The involvement of the intracranial carotid artery course represents a direct risk factor for lesions of the petrous, lacerum and cavernous segments of the carotid artery. Early diagnosis of post-traumatic vascular injury may lead to prognosis improvement because of effectiveness of heparin anticoagulant therapy. Then vascular screening is recommendable in cases with complex fractures of the skull base and particularly fracturing along the course of the carotid artery. Magnetic resonance angiography may be considered the first line diagnostic tools for vascular screening. Angiography may be reserved for patients with a proven lesion or rapid neurological deterioration taking into account the possibility of interventional treatment.

Accidents, Traffic↗

Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results.

OBJECTIVE: The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results. METHODS: Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.0 +/- 1.5 yr). Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immunocytochemical analysis using the monoclonal antibody MIB-1. The Ki-67 antigen labeling index (LI) was determined by counting a total of at least 1,000 neoplastic nuclei. RESULTS: The mean Ki-67 LI for the 101 patients was 2.4 +/- 0.3% (range, 0-23.0%). Only age at surgery was inversely correlated with the Ki-67 LI; sex, maximal tumor diameter, and invasiveness into the cavernous sinuses did not significantly affect the Ki-67 LI. The mean follow-up period was 39.7 +/- 2.1 months. During follow-up monitoring, 23 patients experienced tumor recurrence, after a mean period of 28.6 +/- 4.8 months. Invasiveness of the tumor on preoperative magnetic resonance imaging scans was the strongest predictor of late tumor recurrence, followed by previous pituitary surgery, younger age, and lack of postoperative radiotherapy. The Ki-67 LI had no independent prognostic value. CONCLUSION: Our study suggests that the clinical characteristics of patients with NFPAs, except for age at surgery, are not correlated with the Ki-67 LI. Moreover, the Ki-67 LI does not seem to provide independent information to identify patients at high risk for tumor recurrence.

Adenoma↗

Surgical management of thyrotropin-secreting pituitary adenomas.

The reported cases of hyperthyroidism due to a TSH-secreting pituitary adenoma have steadily increased in previous years; however, information about the results and long term outcome after pituitary surgery is scanty. Twenty-four patients with a TSH-secreting adenoma underwent pituitary surgery at our department in the last 15 years. Hypersecretion of other pituitary hormones was diagnosed in 7 patients. Three patients were euthyroid at the time of surgery because of previous ablative thyroid therapies. The success rate of surgery strictly depends on the criteria used. Normalization of elevated FT3 and FT4 levels occurred in 17 of the 21 patients with preoperative hyperthyroidism: however, only those with early postoperative undetectable TSH level (12 cases) had no recurrence of disease during follow-up and no residual tumor tissue on postoperative MRI, whereas recurrence of hyperthyroidism occurred in 3 of the 5 patients without postoperative TSH inhibition. All 3 euthyroid patients had a subtotal removal of the tumor, as judged by postoperative MRI. Surgical removal is the therapy of choice of TSH-secreting adenomas, whereas radiotherapy and medical treatment with somatostatin analogues are usually reserved to patients with incomplete tumor removal. A thorough postoperative evaluation is necessary to discriminate between complete and partial remission of disease.

Adenoma↗

Usefulness of markers of cell proliferation in the management of pituitary adenomas.

1. Pituitary adenomas are benign and slow-growing tumours whose clinical manifestations depend mainly on the secretory activity of the adenomatous cells. Except for prolactinomas, surgical removal of the tumour is the therapy of choice. 2. Despite extensive research on their clinical and pathophysiological aspects, few studies have explored the oncological characteristics of these rare lesions. Among these, the growth fraction of pituitary adenomas has been determined by different methods, of which the most useful are those performed in archival material. 3. The results reported in the literature show that adrenocorticotropic hormone-secreting tumours seem to be characterized by a higher proliferation index than the other types of pituitary adenomas, despite their usually small tumour size. 4. In small series of patients radiotherapy and medical treatment with dopaminergic drugs and octreotide were associated with a lower proliferation index than untreated tumours. Tumour size was not correlated with the growth fraction of the pituitary tumours, whereas invasiveness was correlated in most studies. 5. From a clinical point of view, however, the more promising utilization of the proliferation index seems to be in predicting the potential of recurrence of the tumour, thus allowing a more rational approach to follow-up and further treatment of patients with pituitary adenomas.

Adenoma↗

Metastatic prostatic adenocarcinoma presenting as a pituitary mass: shrinkage of the lesion and clinical improvement with medical treatment.

BACKGROUND: Metastatic involvement of the pituitary gland is a very unusual presentation of prostatic cancer. We report a favorable response to medical treatment in such a patient. METHODS AND RESULTS: A 77-year-old man presented with blindness, ophthalmoplegia in his left eye, and mild impairment of memory and mental status. Neuroradiological studies showed a huge intra- and suprasellar lesion that destroyed the sellar floor and extended into the sphenoid sinus. Transsphenoidal biopsy of the lesion demonstrated a prostatic adenocarcinoma. Postoperative studies revealed an enlarged prostate gland and multiple lytic bone lesions. The patient was treated with a combination of leuprolide acetate plus flutamide. Four months later, the patient exhibited a marked improvement in his neurologic status and regained vision in the right eye (visual acuity 6/20). Repeat magnetic resonance imaging of the sellar region confirmed a striking shrinkage of the prostatic metastasis. The clinical status remained stable for 22 months, after which time the disease progressed and the patient died 25 months after beginning treatment. CONCLUSIONS: A favorable response to combined androgen blockade suggests that medical therapy should be considered the therapy of first choice when surgical removal of the metastatic lesion in the pituitary is impossible or too risky.

Adenocarcinoma↗

Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels.

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of 111In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 microg octreotide s. c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of 111In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of 111In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 microg octreotide s. c. caused a significant reduction in TSH levels from 4.8+/-1.4 mU/l to a nadir of 3.1+/-1.1 mU/l after 6 h (P<<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that 111In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance.

Adenoma↗

Differentiation of clinically non-functioning pituitary adenomas from meningiomas and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl-spiperone.

The differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods.

Adenoma↗

Oestrogen receptors in meningiomas: a correlative PET and immunohistochemical study.

There have been a number of indications that sex hormones can affect the rate of growth of meningiomas during pregnancy. The presence of oestrogen or progesterone receptors in meningiomas and the influence of sex hormones upon cell cultures derived from human meningiomas have been extensively investigated. The results have been controversial, with most of the discussion centring upon the presence and possible role of oestrogen receptors. The aim of the present study was to assess oestrogen receptors in human meningiomas with 16alpha[l8F]fluoro-17beta-oestradiol ([18F]FES) and positron emission tomography (PET). With this purpose in mind, we measured the regional brain uptake of [18F]FES in six patients with a neuroradiological and histological diagnosis of meningioma, comparing the in vivo PET data with the immunohistological analysis of oestrogen receptors performed on formalin-fixed, paraffin-embedded tissue obtained at surgery. Two analyses were used for the in vivo measurement of [18F]FES binding to oestrogen receptors: the ratio of tumour activity to that of normal tissue (T/NT), calculated 90 min after tracer injection, and the ratio between the equilibrium distribution volume (DV) in normal and pathological tissues, calculated by means of a graphical kinetic analysis. PET studies demonstrated a marked uptake of [18F]FES by the tumour in four of the six patients. Immunohistochemical assay using a manual staining method capable of detecting oestrogen receptors at a level of > 10 pmol mg(-1) of protein detected only sparse immunostaining in one of the six meningiomas. Distinct albeit weak immunostaining was demonstrated in five of the six meningiomas when the sensitivity of the immunohistochemical assay was increased to < 10 pmol mg(-1) of protein by use of an automated staining method (Bioteck 1000). Comparison of the in vivo and immunohistochemical results showed a correlation in five of the six patients, thus indicating the high sensitivity of [18F]FES for the in vivo evaluation of oestrogen receptor expression.

Adult↗

Nerve growth factor suppresses the tumoral phenotype of human prolactinomas.

We summarize here our data showing that various phenotypical characteristics distinguish prolactinoma cell lines obtained from responder and nonresponder patients, as defined by their responses to bromocriptine administration. Nonresponder cell lines have a higher degree of malignancy than responder cells and do not express D2 receptors for dopamine. Both cell lines express NGF receptors. Exposure of the most malignant nonresponder cell lines to NGF, both in vitro and when transplanted in vivo in nude mice, results in their differentiation into the responder phenotype reexpressing D2 receptors. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.

Animals↗