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Piero Picozzi, Nicholas V. Todd and Alan H. Crockard

✓ Cerebral blood volume (CBV) was calculated in gerbils from specific-gravity (SG) changes between normal and saline-perfused brains. Furthermore, changes in CBV were investigated during ischemia using carbon-14-labeled dextran (MW 70,000) as an intravascular marker. Both data were used to evaluate the possible error due to a change in CBV on the measurement of ischemic brain edema by the SG method. The methodological error found was 0.0004 for a 100% CBV change. This error is insignificant, being less than the standard deviation in the SG measured for the gerbil cortex (SG 1.0494 ± 0.0006). Thus, CBV changes are not responsible for the SG variations observed during the first phase of ischemia. These variations are better explained as an increase of brain water content during ischemia.

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Vincenzo Albanese, Antonio Spadaro, Fausto Iannotti, Piero Picozzi, Francesco Tomasello and Fernando Antonio Cioffi

✓ The authors describe a patient in whom a segment of the internal carotid artery (ICA) was coiled. The segment was excised and examined by light microscopy, and transmission and scanning electron microscopy. The elastic tissue in the tunica media of the coiled portion of the artery was absent or greatly reduced and showed no laminar structure. The elastic tissue dysplasia supports the congenital origin of coiling of the ICA.

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Andrea Franzini, Luca Attuati, Ismail Zaed, Shayan Moosa, Antonella Stravato, Pierina Navarria and Piero Picozzi

OBJECTIVE

The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain.

METHODS

Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol–5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months.

RESULTS

Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8–10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8–10) to 5.5 (mean −41.33%, p = 0.01). MPQ scores significantly decreased (mean −22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean −16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively.

CONCLUSIONS

Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.

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Marco Losa, Micol Valle, Pietro Mortini, Alberto Franzin, Camillo Ferrari da Passano, Marco Cenzato, Stefania Bianchi, Piero Picozzi and Massimo Giovanelli

Object. Radiation therapy diminishes the risk of recurrence of incompletely removed nonfunctioning pituitary adenoma (NPA). The authors evaluated the efficacy and safety of gamma knife surgery (GKS) in patients with residual NPA following surgical debulking of the tumor.

Methods. Fifty-four patients, 26 men and 28 women, ranging in age from 29 to 72 years underwent gamma knife treatment. Baseline and follow-up studies involved magnetic resonance imaging, hormone evaluation, and neuroophthalmological examination 6 and 12 months after GKS and at yearly intervals thereafter. The mean follow up after GKS was 41.1 ± 3.1 months. Two of 52 patients undergoing follow up had a recurrence 40 and 49 months after GKS. In both of these patients the treated lesion had reduced in size, but a new lesion appeared in the contralateral side of the sella turcica. The recurrence-free interval at 5 years was 88.2% (95% confidence interval 72.6–100%). Tumor volume decreased from a baseline value of 2.3 ± 0.2 to 1.7 ± 0.2 cm3 at the last follow up (p < 0.001). Twenty-two patients (42.3%) had a 20% or greater reduction in tumor volume. The administered radiation dose had been significantly higher in patients who experienced tumor reduction. Visual function and motility did not deteriorate in any patient. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 12.5, 8.6, and 2.3%, respectively, of assessable patients at risk.

Conclusions. Gamma knife surgery was effective in controlling the growth of residual NPA after previously performed maximal surgical debulking. The major advantage of GKS compared with fractionated radiotherapy seems to be a lower risk of side effects, especially a lower risk of hypopituitarism.

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Piero Picozzi, Marco Losa, Pietro Mortini, Micol Angela Valle, Alberto Franzin, Luca Attuati, Camillo Ferrari da Passano and Massimo Giovanelli

Object. The authors studied the efficacy of gamma knife radiosurgery (GKS) in the prevention of regrowth of nonfunctioning pituitary adenomas (NPA).

Methods. One hundred nineteen patients were included in this study and were divided into two groups. All patients had undergone surgery in our department and recurrent or residual adenoma was demonstrated on postoperative MR imaging. Group A consisted of 68 patients who were followed without additional treatment. Group B was composed of 51 patients who received GKS within 1 year after microsurgery. There was no significant demographic difference between the two groups. In Group B the mean margin dose was 16.5 ± 0.3 Gy (range 13–21 Gy). Fifty one and one tenth percent of patients in Group A were recurrence free at 5 years and 89.8% in Group B (p < 0.001). In Group B patients, tumor volume decreased from a baseline value of 2.4 ± 0.2 cm3 to 1.6 ± 0.2 cm3 at last follow up (p < 0.001).

Conclusions. The results of this study suggest that GKS is effective in controlling growth of residual NPA for at least 5 years following initial maximal surgical debulking compared with no radiation therapy. Thus, GKS is recommended after microsurgery when visible tumor can be detected on imaging studies.

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Alberto Franzin, Giorgio Spatola, Carlo Serra, Piero Picozzi, Marzia Medone, Davide Milani, Paola Castellazzi and Pietro Mortini

Object

Due to technological advances in neuroradiology in recent years, incidental diagnoses of vestibular schwannomas (VSs) have increased. The aim of this study was to evaluate the hearing function after treatment with Gamma Knife surgery (GKS) for VSs in patients adequately selected with “good” or “useful” hearing before treatment and to assess the possible predictive factors for hearing function preservation.

Methods

Of all patients treated in the authors' hospital between 2001 and 2007, they retrospectively studied 50 patients with a unilateral VS in whom there was serviceable hearing (Gardner-Robertson [GR] Class I or II). Additional inclusion criteria were: no Type 2 neurofibromatosis, no previous treatment, and at least 6 months' follow-up of neuroradiological and audiological data. The median patient age was 54 years (range 24–78 years). The median tumor volume was 0.73 ml (range 0.03–6.6 ml), and the median radiation dose to the tumor margin was 13 Gy (range 12–16 Gy) with an isodose of 50%.

Results

Patient age, tumor volume, and presenting symptoms were found to correlate with hearing function. At a median of 36 months after radiosurgery, tumor growth control was 96% and no patient required any other additional treatment. Serviceable hearing was preserved in 34 patients (68%): 21 (62%) with GR Class I hearing and 13 (38%) with GR Class II hearing. The remaining 16 patients had poor hearing function:15 with GR Class III and 1 with GR Class IV hearing function. In 19 (58%) of 33 patients with GR Class I function before GKS the same class was maintained posttreatment; 29 (88%) maintained functional hearing (GR Class I or II). In all patients with an intracanalicular lesion, functional hearing was maintained. Significant prognostic factors for maintaining serviceable hearing were GR Class I function before treatment, symptoms at presentation, patient age younger than 54 years, and Koos Stage T1 disease.

Conclusions

The results of the study show that the probability of preserving functional hearing in patients undergoing GKS treatment for unilateral VSs is very high. Patients with GR Class I, age younger than 54 years, with presenting symptoms other than hearing loss, and a Koos Stage T1 tumor have better prognosis. The prescribed dose of 13 Gy appears to represent an excellent compromise between controlling the disease and preserving auditory function.

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Nicola Boari, Michele Bailo, Filippo Gagliardi, Alberto Franzin, Marco Gemma, Antonella del Vecchio, Angelo Bolognesi, Piero Picozzi and Pietro Mortini

Object

Since the 1990s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect–related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS.

Methods

Of 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm3 (median 1.2 cm3, range 0.013–14.3 cm3), and the median margin dose was 13 Gy (range 11–15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics.

Results

Control of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years.

Conclusions

Gamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

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Alberto Franzin, Alberto Vimercati, Marzia Medone, Carlo Serra, Stefania Bianchi Marzoli, Maddalena Forti, Lorenzo Gioia, Micol Valle and Piero Picozzi

Object

Treatment options for patients with cavernous sinus meningiomas (CSMs) include microsurgical tumor resection, radiotherapy, and radiosurgery. Gamma Knife surgery (GKS) is increasingly being used because it is associated with lower mortality and morbidity rates than microsurgery. The purpose of this study was to assess the role of GKS in the treatment of CSM and to thoroughly analyze the clinical response to GKS.

Methods

Between January 2001 and December 2005, 123 patients (25 men and 98 women; mean age 62.6 ± 11 years, range 31–86 years) who underwent treatment for CSMs were included in this study. Of these, 41 patients underwent microsurgery before GKS, whereas the remaining 82 had GKS as a first-line therapy after a diagnosis was made based on magnetic resonance imaging findings. Dysfunction in cranial nerves (CNs) II, III, IV, V, and VI was noted in 74 patients at the time of GKS. The mean tumor volume was 7.99 cm3 (0.7–30.5 cm3). The mean prescription dose to the tumor margin was 13.8 ± 1.1 Gy (range 10–20 Gy).

Results

The overall tumor control rate was 98.4% with a median follow-up of 36 months. The actuarial tumor control rate at 5 years was 90.5%. A reduction in tumor volume was observed in 53 patients (43.1%), whereas in 68 patients (55.3%) no volumetric variation was recorded. Of the 74 patients who presented with CN deficits, improvement was noted in 23 (31.1%).

Conclusions

Gamma Knife surgery is a useful treatment for CSM both as a first- or second-line therapy. It is a safe and effective treatment for tumors located close to the optic pathways.

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Alberto Franzin, Alberto Vimercati, Piero Picozzi, Carlo Serra, Silvia Snider, Lorenzo Gioia, Camillo Ferrari da Passano, Angelo Bolognesi and Massimo Giovanelli

Object

Treatment options for patients with brain metastasis include tumor resection, whole-brain radiation therapy, and radiosurgery. A single treatment is not useful in cases of multiple tumors, of which at least 1 is a cystic tumor. The purpose of this study was to assess the role of stereotactic drainage and Gamma Knife surgery (GKS) in the treatment of cystic brain metastasis.

Methods

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 ± 11 years, range 38–75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score ≥ 70; and 5) histological diagnosis of a malignant tumor.

Results

Non–small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8–68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2–32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12–25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3–64.1%) and 34.2% (95% confidence interval 23.1–45.3%). Local tumor control was achieved in 91.3% of the patients.

Conclusions

The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis.

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Matthew J. Kuhn, Piero Picozzi, Joseph A. Maldjian, Ilona M. Schmalfuss, Kenneth R. Maravilla, Brian C. Bowen, Franz J. Wippold II, Val M. Runge, Michael V. Knopp, Leo J. Wolansky, Lars Gustafsson, Marco Essig and Nicoletta Anzalone

Object

The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors.

Methods

Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics.

Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (κ > 0.4).

Conclusions

Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.