Presentation of a meningioma in a transwoman after nine years of cyproterone acetate and estradiol intake: case report and literature review.

The administration of cyproterone acetate (CPA) and estradiol is a common regimen used by male-to-female transsexuals (transwoman) to adjust their body to their gender identity. Major adverse events are uncommon in these subjects in spite of long-term, high dose cross-sex steroid treatments. We describe the occurrence of a meningioma in a transwoman treated with estrogens and CPA over a period of nine years. The meningioma was revealed during a magnetic resonance imaging (MRI) scan performed as follow-up of a previous surgery for ganglioglioma. CPA intake was discontinued and tumor resection was performed. Histological diagnosis confirmed a strong progesterone receptor-positive and slight estrogen positive meningioma. After surgery, the patient continued her treatment with leuprorelina acetate and estradiol. At one-year follow-up, the MRI scan reveals no recurrence of the tumor. This is the ninth case in literature of a meningioma in a transwoman treated with estrogens and CPA, confirming a possible association between female sex steroids and meningioma. Although there is no still strong evidence of an association between meningioma and CPA, this report may suggest use of alternative treatment for transwomen. This report highlights the importance to record all the cases of meningiomas in high dose CPA-users, in order to improve data.

Pachymeningeal involvement in POEMS syndrome: MRI and histopathological study.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare plasma cell disease. Vascular endothelial growth factor (VEGF) seems to play a pathogenic role. Peripheral neuropathy is the main neurological feature. Cranial pachymeningitis has occasionally been reported, but no histopathological studies have been performed. The authors extensively evaluated the central nervous system MRI in 11 patients (seven men, four women; mean age at diagnosis 54.45 years) with POEMS syndrome. In two patients, meningeal histopathology with staining for VEGF and VEGF receptor was performed, and pachymeningeal involvement characterised at histopathological, immunohistochemical and confocal microscopy levels. Nine patients presented with cranial pachymeningitis. One patient suffered from migraine, and none complained of cranial nerve palsies or visual loss. None showed any MRI signs of spinal pachymeningitis. No correlation was found with disease duration and VEGF serum level. Histopathology showed hyperplasia of meningothelial cells, neovascularisation and obstructive vessel remodelling, without inflammation. VEGF and VEGF receptor were strongly coexpressed on endothelium, smooth-muscle cells of arterioles and meningothelial cells. In conclusion, POEMS patients present a high prevalence of meningeal involvement. The histological changes, different from those present in chronic pachymeningitis of other aetiology, suggest a possible VEGF role in the pathogenesis of the meningeal remodelling.

Multifocal presentation of medulloblastoma in adulthood.

Medulloblastoma in adulthood is uncommon but not rare; annual incidence is 2-20/1,000,000. Some peculiarities characterize medulloblastoma in adult patients compared with the child type: lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant, and more favourable prognosis. Preoperative diagnosis is crucial for correct management of these patients. However, because of the low incidence of medulloblastoma in the adult population, preoperative diagnosis remains challenging and prognostic factors and best treatment options are still controversial. In this setting, some unusual findings, for example multifocal presentation and extra-axial location, can confound diagnosis and make treatment difficult. We present a short case-illustrated review on these remarkable issues.

A case of squamous cell carcinoma of the scalp after several synthetic hair grafts.

UNLABELLED: In the early 1970s a novel method for hair restoration was described and gained a large following: hair implantation of artificial synthetic fibers. Though popular, the procedure faced numerous criticisms from the scientific community by the early 1980s, and several major and minor complications in a large number of patients treated were reported. However, there were no reports of any neoplasms as complications of artificial hair implantation. Thus, we report our experience with a novel case of long-term cutaneous neoplastic degeneration of an artificial hair implantation procedure in order to provide new insight on the complications related to this procedure. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at http://www.springer.com/00266.

Postoperative seizure in high grade glioma patients treated with BCNU wafers. A mono-institutional experience.

Anticonvulsant therapy is usually recommended before surgery in all patients affected by high grade glioma who are planned to be treated with Carmustine 1,3-bis [2 chloroetyl]-1-nitrosurea, or BCNU) wafers. In fact, phase III studies have reported a risk of seizures higher than 30% in this group of patients. The aim of the study was the evaluation of rate type time of occurrence of seizures in BCNU-treated patients in the postoperative period as well as the investigation into possible risk factors for seizure occurrence in this population. From April 2007 to September 2010, 55 patients underwent surgical removal of malignant glioma and BCNU wafers implantation at the Department of Neurosurgery of Padova. All patients were given antiepileptic prophylaxis for 3 months after surgery. Clinical data (including preoperative seizure history), radiological data, surgical treatment, antiepileptic treatment were retrospectively reviewed. Nine percent of the patients treated with BCNU wafers presented seizures in the postoperative course. Seizures were partial in 80% of cases; they occurred within 30 days after surgery and in 80% of cases within the first 7 days. Patients with preoperative seizures presented more frequently postoperative epilepsy than patients who were preoperatively seizure-free [P = 0.0006; OR = 48 (2,4;945)]. Postoperative seizures were more common among patients affected by one or more wafers related adverse event than among patients without adverse events [P = 0.006; OR = 21 (2,06;213)]; however, they did not appear associated to the number of implanted wafers. Patients with a sub-therapeutic level of AED at the seventh day after surgery presented a higher seizure occurrence [P = 0.02; OR = 11 (1,5;79,8)]. In our experience, postoperative seizures in BCNU-treated patients were less frequent than expected. Careful patient selection and postoperative monitoring could probably play a role in order to decrease seizure occurrence.

The first 3 months after BCNU wafers implantation in high-grade glioma patients: clinical and radiological considerations on a clinical series.

PURPOSE: Carmustine (1,3-bis[2-chloroetyl]-1-nitrosurea (BCNU)) wafers are approved for the local treatment of newly diagnosed and recurrent malignant glioma. Reassuring data on both safety and efficacy of treatment have been previously reported by phase III studies. Although most of related adverse events are reported in the first few months after surgery, there is a lack in the literature of radiological data regarding this period. Few anecdotal experiences have been reported about surgical bed cyst occurrence. The aim of our study is to analyse the radiological course of patients treated with wafers implantation focusing on the relationship between radiological data, and in particular bed cyst occurrence, and safety data. METHODS: Forty-three patients affected by malignant glioma underwent surgical removal and BCNU wafers implantation at the Department of Neurosurgery of Padova from April 2007 to October 2009. Safety data were collected according to previously reported phase III studies. Patients underwent clinical and radiological evaluation (MRI) postoperatively, then before discharge, at 1 month, then every 2 months. In the study were included only patients whose both 1- and 3-month MRIs were available. Finally, 36 out of 43 patients were available for the revision. FINDINGS: Fifty-eight percent of patients treated with BCNU wafers presented a bed cyst of the surgical cave at the 1-month MRI. Forty-eight percent of them were symptomatic. Conversely, among patients who presented one or more adverse event (27%), bed cyst was detected in up to 90% of cases (OR 7.35), being intracranial hypertension more frequently associated (OR 7.35; p value <0.05). In general, cysts presented a benign behaviour in the sense that patients promptly improved with corticosteroid treatment, never required surgery, never reported permanent neurological deficits. CONCLUSIONS: Surgical bed cyst occurrence in BCNU wafer-treated patients resulted more frequent than expected. Familiarity with the event is important to correctly handle a possible evolving phenomenon. However, only further larger experiences and prospective studies could reveal how the understanding of such event might be helpful to improve safety data.

Syringomyelia associated with Chiari I malformation.

An 18-year-old man with progressive paraparesis, thermal hypoesthesia, sweating abnormalities, bladder dysfunction, severe orthostatic hypotension, bilateral Babinski sign, underwent a brain MRI scan that showed downward displacement of cerebellar tonsils through the foramen magnum, consistent with Chiari I malformation, compression of the brainstem-spinal cord junction, and C1-D11 syringomyelia (6.5 mm diameter at C2 level) consistent with Chiari I syndrome. Suboccipital craniectomy and duraplasty were performed. A C2 partial laminectomy and ablation of posterior arch of the atlas was performed. MRI scans 4 days and 1 month after surgery showed a dramatic syringomyelia reabsorption (2.5 and 1 mm, respectively) associated with complete clinical recovery.

Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma.

We compared survival in patients with anaplastic astrocytoma (AA) treated with adjuvant procarbazine, lomustine, and vincristine (PCV) with survival in patients treated with temozolomide. A retrospective analysis was made of patients with newly diagnosed AA treated with adjuvant postradiotherapy chemotherapy. Outcome analysis included progression-free survival and overall survival. The following prognostic factors were taken into account: patient age, extent of resection, performance status, presence of contrast enhancement in presurgical imaging, and type of adjuvant treatment. Among 109 AA patients, 49 were treated with PCV and 60 with temozolomide. The treatment groups were well matched for pretreatment characteristics, except for the presence of contrast enhancement. Age, extent of surgery, performance status, and presence of contrast enhancement were statistically significant prognostic factors according to the Cox model analysis of survival. Type of adjuvant chemotherapy was not a significant factor, either for progression-free survival or for overall survival. Hematological toxicity, nonhematological toxicity grades 3-4, and premature discontinuation due to toxicity were observed in 9%, 3% to 5%, and 37%, respectively, of cases in the PCV group versus 4% to 5%, 0, and 0, respectively, in the temozolomide group. Although the present study was not randomized, it was well designed, and it reports on two homogeneous and consecutive series of patients, for whom histology was verified to obtain survival data only for patients with AA following the recent WHO 2000 classification. Even if no survival advantage has been demonstrated for temozolomide versus PCV, we conclude that temozolomide should be preferred because of its greater tolerability.

The treatment of adults with medulloblastoma: a prospective study.

PURPOSE: To assess in a prospective trial the value of prognostic factors and the outcome of medulloblastoma in adults. METHODS AND MATERIALS: Patients (> or =18 years) with a histologic diagnosis of medulloblastoma were staged according to Chang et al.'s classification (low risk: T1, T2, T3a, M0, and no residual disease after surgery; high risk: T3b-T4, any M+ or postoperative presence of residual tumor). In low-risk patients, treatment consisted of 36 Gy to the craniospinal axis, supplemented by a local tumor dose of 18.8 Gy (total dose of 54.8 Gy). In high-risk patients, 2 cycles of "up-front chemotherapy" were delivered before the same radiation therapy, followed by maintenance chemotherapy if M1, M2, or M3 disease was present. RESULTS: Over a 12-year period, 36 evaluable patients were enrolled. Progression-free survival (PFS) at 5 years was higher in low-risk patients compared to the high-risk group: 76% +/- 14% (95% confidence interval [CI] = 52%-100%) vs. 61% +/- 11% (95% CI = 42%-87%). Patients with M- disease showed a significantly better outcome than M+ patients, with 75% showing PFS at 5 years vs. 45% (p = 0.01). CONCLUSION: The overall PFS observed is comparable to that obtained in pediatric series and suggests that a more effective therapy must be developed for high-risk patients.

Carmustine wafer implantation when surgical cavity is communicating with cerebral ventricles: technical considerations on a clinical series.

BACKGROUND: Implantation of carmustine (1,3-bis (2 chloroetyl)-1-nitrosurea [BCNU]) wafers is an approved local treatment after surgical removal of high-grade gliomas. Safety data have been largely reported by phase III studies. The communication between the final surgical cavity and the ventricular cavities is supposed to be a relative contraindication for positioning of the wafers because of the possible development of hydrocephalus. However, at present there are neither data about this topic published with the exception of a few case reports, nor any proposals for selection criteria for wafer implantation in such circumstances. Furthermore, there are no technical suggestions in literature put forward for the surgical repairing of ventricular defects. Our study was particularly focused on addressing these 3 issues. METHODS: Forty-three patients affected by a high-grade glioma underwent surgical removal and BCNU wafer implantation between March 2007 and September 2009 at the Department of Neurosurgery of Padua. Among them, we retrospectively reviewed clinical, surgical, and radiological data of 9 patients who had been treated with carmustine wafers after surgical repair of communication between the surgical cavity and the ventricular cavities. We also focused on the technical details concerning wafers positioning in this particular situation. RESULTS: Ventricular defects were present in the atrium in 4, frontal horn in 3, and temporal horn in 2 cases. The maximum diameter of the defect was between 6 and 10 mm. In all cases, the defect was intraoperatively repaired in the same way, and up to 8 wafers were implanted in the surgical cavity. In the series reported, no cases of hydrocephalus were detected. CONCLUSIONS: In our experience, integrity of wafers, size of ventricular wall defect, and accuracy in repairing the defect were crucial issues. Nevertheless, more experience and prospective studies would be helpful to clarify both in what measure ventricular opening affects safety data and the best reliable way of repairing ventricular defects when BCNU wafers are implanted.

Bevacizumab and glioblastomas, a single-centre experience: how disease history and characteristics may affect clinical outcome.

BACKGROUND: In 2009, bevacizumab, a monoclonal antibody to vascular endothelial growth factor, received accelerated approval by the United States Food and Drug Administration for the treatment of glioblastoma, based on its high response rate (RR) and 6-month progression-free survival (PFS-6). However, time to progression and overall survival (OS) were disappointing. Since 2008 have been data collected evaluating the safety and efficacy of bevacizumab in patients with relapsed malignant gliomas. PATIENTS AND METHODS: This is a retrospective review of adult patients with recurrent malignant gliomas treated with bevacizumab at a dose of 10 mg/kg every 14 days; some patients were also treated with irinotecan at a dose of 125 mg/m(2) every 14 days. Patients were evaluated for side-effects and clinical outcomes of response, progression and survival. RESULTS: Ten patients received bevacizumab and nine patients received the combination with irinotecan. Both single-agent bevacizumab and combination treatment were well-tolerated. RR was of 28% with no complete responses, PFS-6 was 20% and OS was 4.5 months (95% confidence interval: 3.07-5.98 months). CONCLUSION: Although well-tolerated, the efficacy of bevacizumab was somewhat disappointing, possibly due to the high rate of secondary high-grade gliomas in the studied patient cohort and the late use of bevacizumab in the course of the disease.

A phase II study of cisplatin and temozolomide in heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma.

BACKGROUND: There is pre-clinical evidence of synergism between cisplatin and temozolomide due to higher inhibition of O(6)-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system and in the mechanisms of drug resistance to alkylating agents. PATIENTS AND METHODS: Heavily pre-treated patients with temozolomide-refractory high-grade malignant glioma received cisplatin at a dose of 75 mg/m(2) on day 1 and temozolomide at a dose of 150 mg/m(2) on days 1 to 5 every 21 days until progression or major toxicity. RESULTS: Twenty-four patients were enrolled and a total of 96 cycles were delivered (median for each patient=4). Toxicity was manageable and mostly grade 1-2: haematological, gastroenterological (nausea and vomiting) and fatigue. In patients with glioblastoma, an overall response rate of 29.4% was achieved, with no complete response, and with a disease control rate (responses plus stabilizations) of 64.7%. The median time to progression was 3.8 months (95% confidence interval 2.4-6.8), progression-free survival at 6 months was 28% and overall survival was 7.0 months (95% confidence interval 4.8-11.0). CONCLUSION: The combination of temozolomide and cisplatin is safe and moderately effective in the treatment of heavily pre-treated patients with relapsed high-grade glioma refractory to single-agent temozolomide.

Presurgical (99m)Tc-sestamibi brain SPET/CT versus SPET: a comparison with MRI and histological data in 33 patients with brain tumours.

PURPOSE: A morphofunctional approach to the management of brain tumours has been claimed to increase diagnostic accuracy. Among the proposed single-photon emission tomography (SPET) tracers, (99m)Tc-sestamibi is able to distinguish recurrent tumour from radio-necrosis and to identify early response or resistance to chemotherapy. Major drawbacks of sestamibi, that is, poor morphological resolution and the sites of physiological uptake, could be overcome by dual-modality, integrated systems. The purpose of this study was to investigate the real usefulness of (99m)Tc-sestamibi SPET/computed tomography (CT) and to establish a semiquantitative index. METHODS: Charts from 33 consecutive patients selected for surgery, who underwent preoperative SPET/CT and magnetic resonance imaging (MRI), were reviewed. Tumours were confirmed histologically after the surgery in all patients and classified according to WHO recommendations. Semiquantitative indexes were obtained on images (maximum likelihood expectation maximization reconstructed) with and without attenuation correction and visual analysis of SPET versus SPET/CT was performed. RESULTS: A significant statistical difference was shown between SPET and SPET/CT in terms of the delineation of medial shift, oedema and the ability to distinguish tumour from the skull-meninges complex and plexus. With regard to semiquantitative indexes, a ratio obtained comparing counts/pixel derived from a region of interest in the tumour area with mirrored region of interest in the contralateral site revealed a sensitivity of 90.9% and specificity of 71.45% in discriminating WHO grade 4 gliomas from a lower grade. CONCLUSION: SPET/CT can distinguish tumour from the skull and other sites of physiological uptake better than SPET alone (as confirmed by MRI in all cases) and affords a morphological map. The proposed semiquantitative index also seems promising in identifying higher-grade disease. SPET/CT thus seems a useful additional tool in brain tumour management, especially when MRI is not feasible or PET/CT is not available.

A prospective study on glioblastoma in the elderly.

BACKGROUND: Elderly patients (age > 65 years) with glioblastoma multiforme frequently are excluded from clinical studies, and prospective trials for patients with this age group do not exist to date. METHODS: The authors conducted a prospective trial in 79 consecutive elderly patients with glioblastoma who underwent surgery and received radiotherapy (59.44 grays in 33 fractions; Group A; n = 24 patients) or received the same radiotherapy plus adjuvant chemotherapy with procarbizine, lomustine, and vincristine (PCV; lomustine 110 mg/m(2) on Day 1, procarbazine 60 mg/m(2) on Days 8-21, and vincristine 1.4 mg/m(2) on Days 8 and 29 every 42 days; Group B; n = 32 patients), or received the same radiotherapy plus adjuvant temozolomide (150 mg/m(2) for 5 days every 28 days; Group C; n = 22 patients). RESULTS: The median time to disease progression (TTP) and median survival MST were 7.2 months (95% confidence interval [95%CI], 6.34-8.64) and 12.5 months (95%CI, 11.6-14.8), respectively. The TTP was significantly better for Group C compared with Groups A and B (10.7 months vs. 5.3 months and 6.9 months, respectively; P = 0.0002). Karnofsky performance status (KPS) (P < 0.001) and temozolomide (P < 0.001) were the only independent prognostic factors. Overall survival was better in Group C compared with Group A (14.9 months vs. 11.2 months; P = 0.002), but there were no statistical differences found between Groups A and B or between Groups B and C. Only KPS (P < 0.001) was predictive of overall survival, even if temozolomide chemotherapy was very close to the significance level (P = 0.058). Hematologic Grade 3-4 toxicity was higher with the PCV chemotherapy regimen compared with the temozolomide chemotherapy regimen. CONCLUSIONS: Age alone should not preclude appropriate treatment in elderly patients with good performance status, for whom definitive radiation therapy and adjuvant chemotherapy with temozolomide is advised.