Biomedical subjects

Giovanni Lasio

Publications and source records attributed to Giovanni Lasio.

8 recordsLinked to original sources

PubMed2006

Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage.

CONTEXT: Neurosurgery is regarded as the first-line treatment of acromegaly. Because of its low cure rate in macro and invasive adenoma, the role of primary medical treatment is debated. OBJECTIVE: Our objective was to evaluate primary pharmacological treatment in acromegaly. DESIGN AND SETTING: We conducted an open prospective study at two Italian tertiary level centers. PATIENTS: We studied 67 consecutive patients (36 women; age, 54.9 +/- 14.2 yr; 72% bearing macroadenoma). INTERVENTION: Individually tailored octreotide LAR (OCLAR) was administered. MAIN OUTCOME MEASURES: Outcomes included safe GH (<2.5 mug/liter), normal age-matched IGF-I levels, and tumor shrinkage. RESULTS: After a median follow-up of 48 months (range, 6-108 months), safe GH levels and normal age-matched IGF-I values were obtained by 68.7 and 70.1% of patients, respectively. Hormonal endpoints were achieved regardless of basal levels, and early results were predictive of outcome. Tumor shrank in 82.1% of patients by 62 +/- 31% (range, 0-100%), decreasing from 2101 +/- 2912 to 1010 +/- 2196 mm(3) (P < 0.0001). The higher the basal GH values and the greater the GH/IGF-I changes on treatment, the greater the tumor shrinkage. Tumor disappeared in three patients and was progressively reduced to empty sella in five patients; apparent magnetic resonance imaging cavernous sinus invasion disappeared in three. In males, testosterone increased, restoring eugonadism in 64% of hypogonadal patients. CONCLUSIONS: The efficacy on GH/IGF-I levels in unselected patients and the outstanding volumetric control indicate that treatment with OCLAR may be the first therapeutic approach to all acromegalic patients not amenable to surgical cure. Tumor shrinkage might also encourage the evaluation of primary OCLAR adoption in patients with initial visual field defects.

Acromegaly↗

PubMed2006

NMDA receptor composition differs among anatomically diverse malformations of cortical development.

Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.

Adolescent↗

PubMed2006

Pose estimation of known objects during transmission tomographic image reconstruction.

We address the problem of image formation in transmission tomography when metal objects of known composition and shape, but unknown pose, are present in the scan subject. Using an alternating minimization (AM) algorithm, derived from a model in which the detected data are viewed as Poisson-distributed photon counts, we seek to eliminate the streaking artifacts commonly seen in filtered back projection images containing high-contrast objects. We show that this algorithm, which minimizes the I-divergence (or equivalently, maximizes the log-likelihood) between the measured data and model-based estimates of the means of the data, converges much faster when knowledge of the high-density materials (such as brachytherapy applicators or prosthetic implants) is exploited. The algorithm incorporates a steepest descent-based method to find the position and orientation (collectively called the pose) of the known objects. This pose is then used to constrain the image pixels to their known attenuation values, or, for example, to form a mask on the "missing" projection data in the shadow of the objects. Results from two-dimensional simulations are shown in this paper. The extension of the model and methods used to three dimensions is outlined.

Algorithms↗

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↗

PubMed2004

Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status.

BACKGROUND: Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH-IGF-I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long-acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking. DESIGN: Prospective open trial. PATIENTS: In 19 acromegalic patients with active disease (34-82 years old, seven males, 12 females) resistant to chronic (9-12 months) depot SA (octreotide-LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF-I hypersecretion but no patient had achieved 'safe' GH and normal IGF-I-values. Eight patients had PRL levels greater than 15 micro g/l (range 16-60 micro g/l; 1 micro g = 21.2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients. RESULTS: The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1-3.5 mg/week), decreased GH from 6.6 +/- 0.9 to 4.6 +/- 0.6 micro g/l (P = 0.018), and IGF-I from 552 +/- 44 to 428 +/- 54 micro g/l (P = 0.019) after 6 months (median, range 3-18 Months). Combined treatment decreased GH to < 2.5 micro g/l in four patients (21%) and normalized IGF-I for age in eight patients (42%). It obtained a decline of both GH and IGF-I (-49 +/- 7%, and -47 +/- 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 +/- 8% in four, and IGF-I by 35-38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated. CONCLUSIONS: The addition of cabergoline to depot SA-resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF-I levels in 42% of patients. The association of long-acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.

Acromegaly↗

PubMed2003

Four-year treatment with octreotide-long-acting repeatable in 110 acromegalic patients: predictive value of short-term results?

The effects of a very prolonged treatment with octreotide (OC)-long-acting repeatable (LAR) were retrospectively evaluated in 110 patients with acromegaly, showing a GH/IGF-I decrease of at least 20% vs. baseline after a short-term (6-month) OC-LAR challenge. OC-LAR was given (20 mg, im, every 28 d for 3 injections, then individually tailored) as adjuvant treatment (AT) in 59. The other 51 [primary treatment (PT)] were naive or previously treated by pharmacotherapy. IGF-I normalized in 83 patients [75%; from 770 +/- 26 (mean +/- SE) to 276 +/- 15 micro g/liter; P < 0.0001; median follow-up, 30 months; range, 18-54 months). A progressive increase in the rate of IGF-I normalization was observed. GH fell to less than 2.5 micro g/liter in 72% and to less than 1 micro g/liter in 27% (from 20.7 +/- 2.4 to 2.2 +/- 0.2 micro g/liter; P < 0.0001). PT and AT patients achieved similar final GH/IGF-I levels and rates of normalization. Patients attaining safe GH and normal IGF-I had GH levels below 5 micro g/liter after 3 months and IGF-I levels below 550 micro g/liter after 6 months. No tachyphylaxis was observed. The up-titration to 30 mg improved IGF-I suppression. Elderly patients had greater sensitivity. Tumor shrank in 46% of assessable patients, in 77% of PT patients, and in 91% of naive patients. The powerful suppression of GH/IGF-I levels without tachyphylaxis, the finding of progressive increase in the rate of IGF-I normalization and of superimposable effects in PT and AT patients, and the predictive value of short-term results support the role of PT of acromegaly with OC-LAR in at least some patients.

Acromegaly↗

PubMed2003

Shunt migration into the sphenoid sinus: case report.

OBJECTIVE AND IMPORTANCE: Shunt catheter migration is a potential complication of cerebrospinal fluid shunting procedures. We report an unusual case of proximal shunt migration into the sphenoid sinus. To our knowledge, there have been no previous reports of shunt migration through the bony structures of the cranial base. CLINICAL PRESENTATION: A 41-year-old man who had had a cyst-to-peritoneum shunt placed 21 years earlier for a temporal lobe arachnoid cyst presented with cerebrospinal fluid rhinorrhea. Neuroradiological imaging revealed migration of the shunt catheter through the medial wall of the middle temporal fossa into the sphenoid sinus. INTERVENTION: The patient underwent shunt removal and repair of the dural defect. Intraoperatively, the proximal catheter tip was found in the sphenoid sinus with dural and bony erosion. The patient made an uneventful recovery. CONCLUSION: We present a unique long-term complication associated with intracranial shunt catheters. We hypothesize that excessive proximal catheter length and chronic cerebrospinal fluid pulsations contributed to migration of the catheter into the sphenoid sinus.

Adult↗

PubMed2002

Image-guided endoscopic transnasal removal of recurrent pituitary adenomas.

OBJECTIVE: To assess the role that neuronavigation plays in assisting endoscopic transsphenoidal reoperations for recurrent pituitary adenomas. METHODS: During a 45-month period, 19 endoscopic endonasal transsphenoidal reoperations were performed for recurrent pituitary adenomas. In 11 of 19 patients, the procedure was performed with the aid of an optically guided system. Clinical records were reviewed retrospectively, with attention to the following: comparison of baseline clinical data, the duration of surgery, and the postoperative course and complications of both image-guided and non-image-guided endoscopic reoperations. In addition, to test the reliability of the neuronavigation system, we made measurements of intraoperative accuracy in five additional transnasal endoscopic procedures in "virgin" noses and sphenoidal sinuses. RESULTS: In both groups studied, we found no difference with regard to either morbidity or mortality, which were null. The mean setup time was 13 minutes shorter in non-image-guided procedures (P = 0.021), and the operative time was 36 minutes shorter in image-guided procedures (P = 0.038). No other statistically significant differences were found between the two groups. In all cases, we found that the system performed without malfunction. Continuous information regarding instrument location and trajectory was provided to the surgeon. Measurements of the intraoperative accuracy in the axial, coronal, and sagittal planes indicated a mean intraoperatively verified system error of 1.6 +/- 0.6 mm. CONCLUSION: Neuronavigation can be applied during endonasal transsphenoidal endoscopic surgery and requires a minimal amount of time. It makes reoperation easier, faster, and probably safer.

Adenoma↗