The etiology of low-grade gliomas: pathological and clinical considerations about radiation-induced low-grade gliomas.

The only environmental factor undoubtedly linked to an increased risk of brain tumors (including gliomas) is therapeutic X-rays. We aim to conduct a detailed study of radiation-induced low-grade gliomas, in order to better understand the pathogenesis of such gliomas. Furthermore, we want do prove whether or not there are significant differences, according to clinical features and biological behavior, between this type of tumor and general low-grade gliomas. We analyzed the existent literature of low-grade radiation-induced glioma case reports and other epidemiological reports based on the experience of the senior author. We were able to collect 20 cases of such gliomas. Demographic data and previous X-ray details, along with latency intervals of all patients are provided. The amount of radiation able to cause mutations is not necessarily very high, as tumors occur even after low doses of radiation (as 3-5 GY). The incidence of this kind of tumors may be underestimated and may rise in the future. Care must be taken when observing patients who were irradiated more than 10 years before, especially in the recent years in which access to radiosurgical and radiation therapies has increased in the general population for treating many cerebral pathologies. Radiation-induced low-grade gliomas appear to be different from general gliomas only in terms of age in which they occur. In terms of clinical and biological behavior, there seem to be no differences, even though exceptional cases are reported.

Single brain metastases from cervical carcinoma: report of two cases and critical review of the literature.

Single brain metastases from cervical carcinomas are rare. We report two cases of solitary brain metastases, showing different histological types, which have been excised with microsurgical technique. Neuroendocrine differentiation does not seem to be connected to clinical behavior, indeed a poor prognosis depends on poorly differentiated histological types. In our cases, brain metastases were a late event and they have been successfully excised in microsurgery, thanks to their solitary and resectable nature, and a well-controlled primary disease.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.

Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma.

The aim of this paper is to evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) and concomitant temozolomide (TMZ) as a salvage treatment option in patients with recurrent glioblastoma (GBM). Between May 2006 and December 2009, 36 patients with recurrent GBM received FSRT plus concomitant TMZ at University of Rome La Sapienza, Sant' Andrea Hospital. All patients had Karnofsky performance score ≥60 and were previously treated with standard conformal radiotherapy (RT) (60 Gy) with concomitant and adjuvant TMZ for 6-12 cycles. The median time interval between primary RT and reirradiation was 14 months. At the time of recurrence, all patients received FSRT plus concomitant daily TMZ at the dose of 75 mg/m(2), given 7 days per week from the first day of RT. Radiation dose was 37.5 Gy delivered in 15 fractions over 3 weeks. Median overall survival after FSRT was 9.7 months, and the 6- and 12-month survival rates were 84 and 33%, respectively. The median progression-free survival (PFS) was 5 months, and 6- and 12-month PFS rates were 42 and 8%, respectively. In univariate analysis, KPS (P = 0.04), the interval between primary RT and reirradiation (P = 0.02), and O6-methylguanine-DNA-methyltransferase (MGMT) methylation status at the time of diagnosis (P = 0.009) had an effect on survival; however, in multivariate analysis, only MGMT methylation was statistically significant (P = 0.03). In general, FSRT was well tolerated and the treatment was completed in all patients. Neurological deterioration due to radiation-induced necrosis occurred in three patients (8%). FSRT plus concomitant TMZ is a feasible treatment option associated with survival benefits and low risk of complications in selected patients with recurrent GBM. The potential advantages of combined chemoradiation schedules in patients with recurrent GBM need to be explored in future studies.

Safety and feasibility of the adjunct of local chemotherapy with biodegradable carmustine (BCNU) wafers to the standard multimodal approach to high grade gliomas at first diagnosis.

AIM: Among physicians there is still a reluctant attitude in the employment of combined treatment with surgery and intraoperative placement of carmustina 7.7 mg wafers (Gliadel®), followed by standard adjuvant treatment with radiotherapy and concomitant and subsequent chemiotherapy with temozolomide (TMZ), for supratentorial high grade gliomas at first diagnosis. To determine the safety and feasibility of this multimodality sequential adjuvant therapy, we reviewed our single-institution experience, in the light to provide more insights on this continuous multi-stage chemotherapy approach to such a challenging disease as glioblastoma multiforme. METHODS: From February 2006 to January 2008, 32 patients were treated at our institution for cerebral supratentorial high grade glioma with surgery and intraoperative placement of carmustine wafers. No postsurgical complications could be observed. After a median time of 4,8 weeks all patients began adjuvant concomitant radiotherapy with a mean of 60 Gy and TMZ chemotherapy 75 mg/m2 during which weekly hematologic assessments were performed. After 3 to 6 weeks patients commenced adjuvant TMZ, administered 5 days every 28, 200 mg/m2 for not less than 12 cycles. A contrast-enhanced magnetic resonance imaging (MRI) was routinely performed. Median follow-up after surgery was of 6.5 months, ranging from 4 to 23 months. RESULTS: The mean presurgical KPS was of 80 (range: from 60 to 100), and it remained unmodified after adjuvant therapies even at suspension of steroids. In 4 cases there was a radiologic evidence of progression of the disease and the necessity of steroids, with a progression-free survival (PFS) of 6, 8, 9,5 and 13,6 months. One case died 14 months after first operation. All other patients are still alive. CONCLUSION: The integration of local chemiotherapy with carmustine wafers and the standard adjuvant regimen with radiotherapy and concomitant chemiotherapy appears to be safe and feasible, without any adjunctive complication. Promising results on the efficacy require more follow up to be quantified.

Sarcoma metastatic to the brain: a series of 35 cases and considerations from 27 years of experience.

The authors report their 27-year experience regarding 35 cases of supratentorial brain metastasis from sarcoma treated in a single institution: these included ten osteosarcomas, seven leiomyosarcomas, five Ewing sarcomas, four malignant fibrous histiocytomas, three alveolar soft-part sarcomas (ASPS), two rhabdomyosarcomas, one liposarcoma, and three unclassified sarcomas. The first 15 cases of the series have already been described in a previous publication. Median survival after craniotomy was 9.8 months (range: 4-24). In patients with preoperative Karnofsky performance score (KPS) > 60 it was 12.8 months (range: 6.5-24 months) versus 5.4 months for those patients with a KPS < or = 60 (P = 0.01). Eight patients had more than one lesion, six of which were treated in the last ten years. Of the three patients with ASPS, the first two were alive at 15 and 20 months (before being lost to follow-up) whereas the third patient is alive at 24 month follow-up. The authors conclude that surgery is more effective in treating selected patients with sarcoma metastatic to the brain, and that patients with metastasis from ASPS have good prognosis when submitted to surgical treatment. The complete removal of all brain metastases "en bloc" and a KPS > 60 are associated with the best prognosis. Finally, it seems that surgical indications for multiple brain metastases from sarcoma have increased during the last ten years.

Preterm delivery and premature rupture of membranes after conization in 80 women. Preliminary data.

AIM: Cervical intraepithelial neoplasia is most frequently in young women in reproductive age. Cold knife conization, laser ablation, laser conization and large loop excision are conservative methods of treatment to remove the transformation zone and preserve the cervical function. Previous studies have shown conflicting results on the outcomes of pregnancy following these therapies that might increase the risk of preterm delivery. The purpose of this study was to evaluate the outcome of pregnancy after conization and its role as predictive risk factor. METHODS: A retrospective study was performed. The study group comprised 80 women who had a conization and that had a subsequent singleton pregnancy. Variables considered includes maternal excision date, surgery procedure, previous surgery treatments, time interval between excisional procedure and subsequent pregnancy; duration and week of pregnancy, mode of delivery, histological grading (no cervical intraepithelial neoplasia [CIN], CIN 1, CIN 2-3) and cone excised depth. RESULTS: In group study 45 women underwent loop electrosurgical excision procedure (LEEP) conization, 32 cold knife conization and 3 laser CO2. The authors found 11 cases of cone tissue depth<1 cm, and remaining one>1 cm. Eight preterm delivery have been reported to data: 5 between 28 and 34 weeks, 2 lower than 28 weeks and 1 between 34 and 37 weeks. CONCLUSION: In these preliminary data the percentage of preterm birth appears as 10% and in range 6-15% evaluated for women not submitted to excisional procedures.

Elderly and poor prognosis patients with high grade glioma: hypofractionated radiotherapy.

AIM: To evaluate efficacy of short-course radiotherapy in elderly and/or poor performance status patients with high grade glioma. MATERIALS AND METHODS: Twenty-one patients with high grade astrocytoma were selected in our Institute to receive hypofractionated radiotherapy. We considered two radiotherapy treatment arms: in arm I there were 22 patients treated with 60 Gy in 30 fractions at 5 fractions per week; in arm 2 there were 21 patients who received hypofractionated radiotherapy course of 30 Gy in 10 fractions at 5 fractions per week. RESULTS: In arm1 the median survival time was 8.2 months and the 1 year overall survival was 36%; in arm 2 the estimated median survival was 6.2 months and the 1 year overall survival was 23%. Treatment was without acute toxicity. CONCLUSIONS: In our experience, hypofractionated radiotherapy seems to be a reasonable treatment option for poor prognosis patients with high grade astrocytoma. It is well tolerated and can reduce the overall treatment time without negative effects on survival compared with conventional fractionation.

Gliomatosis cerebri treatment in 11 elderly patients.

The Authors report their experience in the treatment of eleven patients over 70 years old (range from 70 to 83, average age 74.8, 7 males and 4 females), with histologically proven diagnosis of glioblastoma multiforme. The GC golden standard treatment is still debated, particularly in elderly patients. All the patients underwent a first line treament with chemotherapy (Temozolomide), followed by Whole Brain Radiotherapy (WBRT) and PCV schedule without Vincristine in case of progression of the disease. The median survival was 16.3 months, ranging from 13 to 22 months. According to our experience, elderly patients should undergo the same treatment of younger patients, provided they are in good health conditions.

Paragangliomas of the cauda equina. Report of one case and review of the literature.

The authors report one case of cauda equina paraganglioma and review the neurosurgical, radiological and pathological literatureon this rare tumour. Although it is difficult to distinguish preoperatively the paraganglioma from other tumours of the cauda equina, like neurinoma or ependymoma, this neuroendocrine tumour should be included in differential diagnosis.

Sylvian subarachnoid and extra-pial cavernous angioma.

Cavernous angiomas are one of the four types of vascular malformations of the central nervous system. Lesions situated subarachnoidally are rare although some cases with an infratentorial localization have been reported. Our case represents an unusual localization of a subarachnoid cavernous angioma. A 35- year-old patient was admitted to our department with signs of subarachnoid hemorrhage. A 1 cm hyperdense lesion placed at the right Sylvian fissure was distinguished by CT-scan examination and no arterial supply was revealed on cerebral angiography. Surgical intervention showed a lesion placed extra-pial and totally encased in the subarachnoid space in the superficial part of the Sylvian cistern. This case represents a radiologically visible supratentorial extra-pial subarachnoidal cavernous angioma. This case provides confirmation of one of the supposed causes of subarachnoid hemorrahage ''sine materia''.

Central nervous system mesenchymal chondrosarcoma.

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature.

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.

Surgical strategies in the treatment of symptomatic osteomas of the orbital walls.

We present a series of 19 surgically treated osteomas involving the orbital walls. Eight were localized at the junction of the frontal sinus and orbital roof, three were frontoethmoidal, two were of the orbital roof, one of the lateral wall, one of the orbital floor, and four involved all the walls of the orbit and were termed panorbital. All tumors at the junction of the frontal sinus and the orbital roof as well as those originating from the orbital roof proper were removed by frontal craniotomy. In the three that were frontoethmoidal, osteotomies were performed. Lateral and inferior orbitotomies were done when the corresponding orbital walls were affected. The four panorbital osteomas required large frontotemporal craniotomies in association with superolateral orbitotomy and zygomatic and/or malar osteotomy, when necessary. Satisfactory cosmetic and functional results were obtained in all but two cases of panorbital osteomas, in which the neurological deficit worsened after surgery. We discuss the choice of the various approaches described, with reference to the relevant literature.

Spinal glioblastomas: report of seven cases and review of the literature.

Intramedullary glioblastomas are uncommon tumors. They occur chiefly in the cervicothoracic segments, have a slight tendency to occur in the early decades of life, and have a short clinical history before diagnosis. We report seven cases and discuss the salient features of these tumors, particularly the pathological features and treatment, in light of the relevant literature.

Isolated lesion of the axillary nerve: surgical treatment and outcome in 12 cases.

We report a series of 12 cases of isolated lesions of the axillary nerve treated surgically. We discuss the pathogenesis, clinical pattern, and surgical treatment of this lesion together with the results obtained.

A two-step supraorbital approach to lesions of the orbital apex. Technical note.

A two-step supraorbital approach to lesions of the orbital apex is described. This technique is easy and allows a satisfactory exposure of the region. In addition, the reconstruction resulting from the procedure is anatomically perfect. The authors report the operative results obtained in 20 patients and compare this two-step supraorbital procedure with similar surgical techniques described previously.

Symptomatic cervicogenic headache.

Cervicogenic headache is a little-known clinical condition whose true importance has only recently been recognized. A number of causes may lie at the basis of the onset of headache (symptomatic cervicogenic headache). However, despite exhaustive attempts, sometimes it is not possible to identify a clear cause responsible for the onset of the syndrome (primitive cervicogenic headache). The genesis of symptomatic cervicogenic headaches sometimes may be easy to identify as a result of a close, pre-existing, cause-effect relationship (i.e. trauma). On other occasions it may be much more laborious to pinpoint the pathology responsible for headache (some cranio-cervical anomalies, etc.). Clinically, it is necessary to perform a thorough preliminary clinical and anamnestic evaluation which can orient subsequent investigations to achieve a diagnosis in the least time possible with the minimum discomfort to the patient and his relatives, not to mention lower costs for society.

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial.

BACKGROUND: Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only. PATIENTS AND METHODS: Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial. In phase I of the study, TMZ (75 mg/m2/day per 7 days/wk for 6 weeks) was orally administered to patients concomitantly with radiotherapy (RT) (2 Gy per fraction once daily, per 5 days/wk for 6 weeks). In phase II of the study, four weeks after completion of RT, a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles. Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry. RESULTS: The one-year survival rate of patients treated with the investigated multimodality treatment was 58% and median survival time was 15.7 months. Concomitant RT plus TMZ (phase I) followed by adjuvant TMZ (phase 2) were well-tolerated; indeed, nonhematological adverse events were rare and mild to moderate in severity; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II. We found that the combination of radio- and chemo-therapy, in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study. CONCLUSION: The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients' quality of life.