Chrissa Sioka

Chemotherapy, hormonal therapy, and immunotherapy for recurrent meningiomas

Meningioma is a common intracranial tumor, originating from the meninges of the skull or spinal canal. Most meningiomas are benign tumors, however atypical or anaplastic tumors can be found in 6% of cases. Patients with asymptomatic small benign meningiomas can be followed without therapy, but in symptomatic patients complete surgical resection should be performed. For recurrent previously resected tumors re-resection is recommended followed by radiotherapy in selected cases. Antiprogesterone treatment can also be considered in recurrent benign meningiomas. Immunotherapy with interferon-alpha and chemotherapy should be reserved for all cases of recurrent meningiomas (benign, atypical, and malignant) when all the standard therapies have failed or contraindicated.

Inherited predisposition to glioma.

In gliomas, germline gene alterations play a significant role during malignant transformation of progenitor glial cells, at least for families with occurrence of multiple cancers or with specific hereditary cancer syndromes. Scientific evidence during the last few years has revealed several constitutive genetic abnormalities that may influence glioma formation. These germline abnormalities are manifested as either gene polymorphisms or hemizygous mutations of key regulatory genes that are involved either in DNA repair or in apoptosis. Such changes, among others, include hemizygous alterations of the neurofibromatosis 1 (NF1) and p53 genes that are involved in apoptotic pathways, and alterations in multiple DNA repair genes such as mismatch repair (MMR) genes, x-ray cross-complementary genes (XRCC), and O6-methylguanine-DNA methyltransferase (MGMT) genes. Subsequent cellular changes include somatic mutations in cell cycle regulatory genes and genes involved in angiogenesis and invasion, leading eventually to tumor formation in various stages. Future molecular diagnosis may identify new genomic regions that could harbor genes important for glioma predisposition and aid in the early diagnosis of these patients and genetic counseling of their families.

Vitamin D receptor gene polymorphisms in multiple sclerosis patients in northwest Greece

BackgroundPolymorphisms of the vitamin D receptor (VDR) gene have been linked to both multiple sclerosis (MS) and osteoporosis. We examined the frequency of the Taq-I and Bsm-I polymorphisms of the vitamin D receptor (VDR) gene in 69 patients with MS and 81 age and sex-matched healthy individuals. Genotyping of Taq-I (rs731236) and Bsm-I (rs1544410) was performed using TaqMan® SNP Genotyping Assay. All patients and controls had determination of body mass index (BMI), bone mineral density (BMD) and smoking history.ResultsThe mean age of patients was 39 ± 10.5 years compared to 38.7 ± 10.7 years of the controls (p = 0.86), the BMI was 24.8 ± 4.2 kg/m2 compared to 25.7 ± 4.8 kg/m2 of the controls (p = 0.23), the BMD in the lumbar spine 0.981 ± 0.15 compared to 1.025 ± 013 of the controls (p = 0.06) and the total hip BMD was 0.875 ± 0.14 compared to 0.969 ± 0.12 of the controls (p < 0.001). There were no differences of the Taq-I (TT, CT, CC) and Bsm-I genotypes (GG, GA, AA) and allelic frequencies between MS and control individuals. Multivariate analysis also failed to show any association of the Taq-I and Bsm-I polymorphisms and MS or sex, BMI, BMD and smoking history.ConclusionsThis study suggests that the Taq-I and Bsm-I polymorphisms of the VDR gene are not associated with MS risk, BMI or BMD in the Greek population studied.

Body Composition in Ambulatory Patients With Multiple Sclerosis

The aim of this study was to compare between ambulatory patients with multiple sclerosis (MS) and control subjects, bone mineral density (BMD), and body composition, that is, percent of bone minerals (M%), fat (F%), and remaining substances (L%). Total body composition and BMD were measured by dual-energy X-ray absorptiometry in 68 patients with definite MS and Expanded Disability Status Scale (EDSS) score ≤ 6.5 (41 females and 27 males) and 114 control individuals (72 females and 42 males). The amount of F%, L%, M%, and BMD in the whole body, arms, and trunk was not statistically different between MS patients (males and females) and controls, except in the lower extremities of female patients where there was increased F% and reduced L% compared with controls. There were no correlations between F%, L%, M%, and BMD at any anatomic region with EDSS or the cumulative corticosteroid dose. The reduced L% in the lower extremities of female patients suggests a possible increased subsequent risk of osteoporosis in the legs. Brief steroid courses administered during disease exacerbations in ambulatory MS patients did not result in obvious adverse consequences.

Recent advances in PET imaging for evaluation of Parkinson’s disease

Parkinson’s disease (PD) consists of loss of pigmented dopamine-secreting neurons in the pars compacta of the midbrain substantia nigra. These neurons project to the striatum (putamen and caudate nucleus) and their loss leads to alterations in the activity of the neural circuits that regulate movement. In a simplified model, two dopamine pathways are involved: the direct pathway, which is mediated through facilitation of the D1 receptors, and the indirect pathway through D2 receptors (inhibitory). Positron emission tomography (PET) tracers to image the presynaptic sites of the dopaminergic system include 6-[18F]FDOPA and 6-[18F]FMT, [11C]dihydrotetrabenazine, [11C]nomifensine and various radiolabelled cocaine derivatives. Postsynaptically, for the dopamine D1 subtype the most commonly used ligands are [11C]SCH 23390 or [11C]NNC 112 and for the D2 subtype [11C]raclopride, [11C]MNPA and [18F]DMFP. PET is a sensitive and specific non-invasive molecular imaging technique that may be helpful for evaluation of PD and its differential diagnosis from other parkinsonian syndromes.

Effects of I-131 therapy on gonads and pregnancy outcome in patients with thyroid cancer

We examined the effects of I-131 therapy for thyroid cancer on female and male gonads and pregnancy outcome. After an extensive review of the published literature we concluded that ablative administration of I-131 therapy may result in transient abnormalities of ovarian and testicular function, but subsequent pregnancies are safe without any significant consequences to offspring outcome.

Paraneoplastic Neurological Syndromes and the Role of PET Imaging

Paraneoplastic neurological syndromes are immune-mediated effects of cancer that involve the nervous system and are associated with various anti-neuronal antibodies. They can be associated with several cancers such as lung, gynecologic, thymic, testicular and others, but the diagnosis of cancer often becomes a challenge, since paraneoplastic neurological syndromes usually precede the cancer presentation by months or even years. Furthermore, even when the cancer develops, the tumor size remains small and usually undetectable by conventional diagnostic tests and imaging. Positron emission tomography imaging may be an adjunct to timely diagnosis of the occult malignancy in order to employ the specific cancer treatment. Furthermore, positron emission tomography can assess the extent of the functional abnormality in the brain and monitor its response to treatment.

The utility of FDG PET in diagnosis and follow-up of lymphoma in childhood

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are among the most common malignancies of childhood. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can be employed for accurate staging, treatment planning, and response assessment in pediatric patients with lymphomas, taking advantage of the increased FDG uptake of the malignant cells, secondary to their increased metabolic needs. FDG PET has higher sensitivity than other imaging modalities to detect nodular or diffuse lesions and higher sensitivity than bone marrow biopsy to detect bone marrow infiltration. FDG PET consists of an invaluable imaging modality during evaluation and treatment of pediatric lymphomas.

Myocardial perfusion imaging with 99 mTc - tetrofosmin SPECT in breast cancer patients that received postoperative radiotherapy: a case-control study

PurposeTo evaluate the cardiac toxicity of radiotherapy (RT) in breast cancer (BC) patients employing myocardial perfusion imaging (MPI) with Tc-99 m Tetrofosmin - single photon emission computer tomography (T-SPECT).Materials and methodsWe studied 46 BC female patients (28 patients with left and 18 patients with right BC) treated with postoperative RT compared to a control group of 85 age-matched females. The median time of RT to SPECT was 40 months (6-263).ResultsAbnormalities in the summed stress score (SSS) were found in 54% of left BC patients, 44.4% of right BC patients, and 32.9% of controls. In left BC patients there were significantly more SSS abnormalities compared to controls (4.0 ± 3.5 vs 2.6 ± 2.0, p = 0.05) and possible trend of increased abnormalities of right BC patients (3.7 ± 3.0 vs 2.6 ± 2.0, p = 0.14). Multiple regression analysis showed more abnormalities in the MPI of left BC patients compared to controls (SSS, p = 0.0001); Marginal toxicity was also noted in right BC patients (SSS, p = 0.045). No additional toxicity was found in patients that received adjuvant cardiotoxic chemotherapy. All T-SPECT abnormalities were clinically silent.ConclusionThe study suggests that radiation therapy to BC patients result in MPI abnormalities but without apparent clinical consequences.

The diagnostic role of 18F fluorodeoxyglucose positron emission tomography in patients with fever of unknown origin

Identification of aetiology for fever of unknown origin (FUO) is challenging, due to the high rates of undiagnosed cases. The current diagnostic approach includes initially first‐line procedures such as general examination and various laboratory tests and basic imaging techniques followed by second‐line tests such as more advanced imaging techniques including 18F fluorodeoxyglucose positron emission tomography (FDG PET) and tissue biopsies. If no diagnosis is obtained, more invasive measures may be in order such as liver biopsy and exploratory laparotomy.