Alfredo Pompili

End of life issues in brain tumor patients

Despite aggressive antitumor treatment, the prognosis of brain tumor (BT) patients remains poor. In the last stage of disease, BT patients present severe symptoms due to the growing tumor or to treatment side-effects, which require adequate palliative management and supportive therapy. However, studies specifically addressing palliative care and end-of-life (EoL) issues in BT patients are lacking. This study explores symptoms experienced by BT patients in the last weeks of disease and EoL issues observed in a population of brain tumor patients followed at home until death by a neuro-oncological home care palliative unit set up in our Institution in 2000. From October 2000 to December 2005, 324 patients affected by brain tumor and discharged from our Institution were enrolled in a comprehensive program of neuro-oncological home care supported by the Regional Health System. Out of 324 patients enrolled in the home care program, 260 patients died of which 169 (65%) were assisted at home until the end of life and have been included in this study. Clinical symptoms, palliative treatments and EoL treatment decisions were collected from home clinical records. Among the 169 patients assisted at home until death, the most frequent symptoms observed in the last four weeks of life were: epilepsy 30%, headache 36%, drowsiness 85%, dysphagia 85%, death rattle 12%, agitation and delirium 15%. Palliative management of brain tumor patients requires a multidisciplinary approach performed by a well trained neuro-oncology team. Development of home care models of assistance may represent an alternative to in-hospital care for the management of patients dying of brain tumor and may improve the quality of end-of-life care.

Multiple Sclerosis Plaque Simulating Cerebral Tumor: Case Report and Review of the Literature

Multiple sclerosis rarely may present as a focal cerebral mass with clinical features and computed tomographic scan appearances of cerebral tumor. Distinguishing between these can be difficult or impossible. We report a case of a multiple sclerosis plaque involving the parietal lobe with mass effect; clinical and radiological features had led to a diagnosis of cerebral tumor.

Quality of Care and Rehospitalization Rate in the Last Stage of Disease in Brain Tumor Patients Assisted at Home: A Cost Effectiveness Study

UNLABELLED Despite aggressive multimodality treatment the prognosis of patients with primary brain tumors (BT) remains poor. At present, there are no data about the role of palliative home-care services and their impact on quality of care. We report the results of a pilot project of palliative home care for BT patients started in 2000 in the National Cancer Institute Regina Elena of Rome. We report also the result of a cost/effectiveness analysis utilizing administrative data on re-hospitalization rate in the last two months of life. METHODS Since October 2000 until December 2009, 572 patients have been followed by our home care staff. Among 394 patients who died, 276 (70%) were followed at home until death. A cost/effectiveness analysis was carried out evaluating the rehospitalization rate in the last 2 months of life in a subgroup of patients (group 1 assisted at home, 72 patients; group 2 not assisted at home, 71). The number of hospital readmission in the last 2 months of life, and length and cost of hospitalization were retrospectively analyzed from hospital discharge records. RESULTS Hospitalization rate of group 1 (16.7%) was lower than group 2 (38%) (95% CI: 0.18-0.65, p = 0.001). Costs of hospitalization also differed substantially: 517 Euros (95% CI: 512-522) in group 1 vs 24, 076 Euros (95%: 24,040-24,112 Euros) in group 2. CONCLUSION Home-care may represent an alternative to in-hospital care for the management of brain tumor patients and may improve the end-of-life quality of care.

Unilateral limited laminectomy as the approach of choice for the removal of thoracolumbar neurofibromas

Study Design. The paper reports a minimally invasive approach to the dorsolumbar spine for the removal of neurofibromas. Objectives. Demonstrating that a limited unilateral approach is the one of choice for this kind of tumors. Summary of Background Data. Spinal intradural extramedullary tumors are generally removed by single-level or multilevel laminectomy with midline dural incision. Cases of delayed postoperative kyphosis and spinal instability (6%) may be reduced by unilateral microsurgery, causing minimum damage to ligaments and joints. Methods. Ten patients with dorsolumbar neurofibroma were operated on between June 2000 and June 2002. There were 5 males (all with lumbar) and 5 females (2 with lumbar and 3 with inferior dorsal neurofibromas). One female had 3 lumbar tumors and required two operations. Surgery was performed in the prone position with a unilateral approach, sparing the joint and the ligamentum interspinosum. The dura was opened paramedially and the tumor dissected from the root and removed in one piece when possible. Water-tight dural closure was done with 5–0 or 6–0 stitches. Results. All the patients were mobilized on day 2 and discharged on day 4 or day 5. No complications resulting from the technique were observed. Static and dynamic plain radiograph films showed that none of them had kyphosis and/or instability 6 months postoperatively. Neurologic results were good. Conclusions. Hospital stay may be reduced and stability may be preserved with an appropriate microsurgical technique. The technique reported in the paper should thus become the one of choice and extended to other spinal intradural extramedullary tumors.

CCNU-chemotherapy of hemispheric supratentorial glioblastoma multiforme

One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied. All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made. Patients were randomly placed in one of three treatment schedules within 3 weeks of surgery: Group A: combined radiation therapy and drug (CCNU) therapy (26 cases); Group B: CCNU given orally every 6–8 weeks (27 cases); Group C: standard radiation therapy alone (50 cases). All patients were periodically controlled by clinical and instrumental (EEG, scan, EMG, CAT) evaluations; laboratory data examinations were also frequently performed. The treatment results have been evaluated according to length of survival, social quality of life, and positive or negative response to chemotherapy. In our opinion the clinical findings are interesting but the statistical results are somewhat negative, especially when the groups of patients are not homogeneous.

Epigenetic silencing of miR-145-5p contributes to brain metastasis.

Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145s promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.

The transdural extension of gliomas

The extraneural spreading of gliomas is an infrequent occurrence which is not necessarily related to either tumor histology or site.This paper reports two cases, a glioblastoma and an oligodendroglioma, both presenting extradural diffusion. In the first case, where there was severe intracranial hypertension, the tumor found its way out from the neurocranium, far from the site of the operation, perforating the dura and the bone of the cranial base. In the second case, the operation may have facilitated the extraneural invasion.This unusual behaviour of glial tumors is probably less rare than presumed. It may go unnoticed if the attention is concentrated on the usually severe neurological syndrome which is present in these patients.

Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy: a pilot study

ObjectiveAn open pilot study to evaluate the effect of pregabalin (PGB) as add-on therapy on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy (BTRE).Materials and methodsWe recruited 25 consecutive patients with BTRE and uncontrolled seizures. At baseline and during follow-up, patients underwent a complete physical and neurological examination and were evaluated using the QOLIE 31P (V2), EORTC QLQ C30, Adverse Events Profile, and Hamilton Anxiety Rating Scale (HAM-A). At baseline, a seizure diary was given.ResultsDuring follow-up, 17 patients underwent chemotherapy, none underwent radiotherapy, 9 had disease progression, and 3 died. Mean duration of follow-up was 4.1 months. Mean PGB dosage was 279 mg/day. At baseline, mean weekly seizure frequency was 5.3 (±10) and at last available follow-up visit was 2.8±5. This difference was statistically significant (p=0.016). The responder rate was 76%. Ten patients dropped out; 4 as a result of seizure worsening, 1 as a result of unchanged seizure frequency, 3 as a result of a lack of compliance, and 2 as a result of side effects. Based on the QOLIE-31-P, a significant improvement of the subscale “seizureworry” (p=0.004) and a significant decrease in distress scores related to AEDs and social life (p=0.009 and p=0.008, respectively) were observed. A significant decrease in HAMA score (p=0.002) was documented.ConclusionsThese data indicate that PGB may represent a valid alternative as add-on treatment in this patient population, based on its efficacy on seizure control and anxiety.

Spontaneous cerebrospinal fluid rhinorrhea as the presenting symptom of sellar pathologies: three demonstrative cases

Spontaneous rhinorrhea due to sellar pathologies is a rare and insidious disease that may represent a diagnostic challenge. Since the precipitating cause is not apparent in most patients, delayed diagnosis and/or improper treatments are not uncommon and may be detrimental for the patients. The precise mechanisms of such rhinorrhea are still incompletely understood. Proposed etiological factors include constant cerebrospinal fluid pulsations against the anterior skull base trasmitted by primitive or acquired arachnoid invaginations in combination with either elevated ICP or congenital/pathologic erosions of sellar and parasellar bone structures. Advances in the diagnosis and surgical techniques have recently modified the decision-making approach to this pathology. The present paper reports three unusual cases of sellar pathologies revealed by rhinorrhea as the first symptom discussing controversial issues on pathogenesis, complications and current management of this kind of fistula.

Perfusion Computed Tomography (PCT) adopting different perfusion metrics: Recurrence of brain metastasis or radiation necrosis?

OBJECTIVE Different perfusion metrics were investigated to determine the accuracy of Perfusion CT (PCT) in differentiating recurrence of brain metastases from radiation necrosis in patients who previously underwent stereotactic radiation therapy (SRT). PATIENTS AND METHODS Twenty patients previously treated with SRT underwent PCT examination of the brain. Normalized Cerebral Blood Volume (nCBV) values within the region of interest (ROI) were calculated. Fractional volumes at nCBV values between 1.0 and 2.25, defined as V(1.0)-V(2.25), were derived as alternative metrics and compared to the conventional method based on the mean CBV value within the lesion (nCBV(mean)). The Mann-Whitney test was used to compare the two patients groups with recurrence and radiation necrosis with respect to the different nCBV metrics. Predictive powers and optimal thresholds for both the nCBV(mean) and the V(1.0)-V(2.25) were evaluated using the Receiver Operating Characteristic Curves. The gold standard was represented either by the histopathological examination or the Magnetic Resonance (MR) imaging follow-up longer than six months. RESULTS AND CONCLUSION The differences between the patients group with recurrence and that with radiation necrosis resulted statistically significant for all the metrics, showing the lowest p-value for V(1.75) and V(2). The metrics based on the fractional volumes were found to show higher predictive powers, with the highest value of 0.96 for V(2.0). Quantitative analysis of the CBV map deriving different metrics may potentially improve the diagnostic accuracy of PCT in differentiating brain metastasis recurrence from radiation necrosis.