Andreas Fotopoulos

Glioma recurrence versus radiation necrosis: accuracy of current imaging modalities

Treatment for brain gliomas is a combined approach of surgery, radiation therapy and chemotherapy. Nevertheless, high-grade gliomas usually recur despite treatment. Ionizing radiation therapy to the central nervous system may cause post-radiation damage. Differentiation between post-irradiation necrosis and recurrent glioma on the basis of clinical signs and symptomatology has not been possible. Computed tomography (CT) and magnetic resonance imaging (MRI) suffer from significant limitations when applied to differentiate recurrent brain tumor from radiation necrosis. We reviewed the contribution of recent MRI techniques, single-photon emission CT and positron emission tomography to discriminate necrosis for glioma recurrence. We concluded that despite the progress being made, further research is needed to establish reliable imaging modalities that distinguish between true tumour progression and treatment-related necrosis.

The Effects of Chronic Treatment with Octreotide versus Octreotide plus Midodrine on Systemic Hemodynamics and Renal Hemodynamics and Function in Nonazotemic Cirrhotic Patients with Ascites

OBJECTIVES:The adrenergic agonist midodrine improved circulatory and renal dysfunction when acutely administered in nonazotemic cirrhotic patients with ascites while its combination with octreotide has recently been proposed as an effective treatment of type 1 hepatorenal syndrome (HRS). However, the effects of octreotide on systemic hemodynamics and renal function in cirrhotic patients are controversial. This study evaluated the effects of chronic treatment with octreotide versus octreotide plus midodrine on systemic hemodynamics and renal hemodynamics, and function in nonazotemic cirrhotic patients with ascites.METHODS:Twenty-five patients were studied at baseline and 11 days after administration of subcutaneous octreotide 300 μg, b.i.d. alone (n = 12) or together with oral midodrine 7.5 mg, t.i.d. (n = 13).RESULTS:Octreotide did not improve systemic hemodynamics whereas the addition of midodrine significantly decreased cardiac index (CI) and heart rate (HR), and increased mean arterial pressure (MAP) and systemic vascular resistance (SVR). Octreotide caused a decrease in renal vascular resistance (RVR) and increased renal blood flow (RBF) but significantly reduced glomerular filtration rate. The association of midodrine to octreotide did not modify renal hemodynamics and function as compared to baseline while it caused an almost significant minor increase in RVR and a significant minor decrease in RBF as compared to octreotide alone. Consequently, a significant minor increase in glomerular filtration rate was demonstrated. The plasma values of active renin, aldosterone, and glucagon were significantly reduced in either group.CONCLUSIONS:Octreotide does not improve systemic hemodynamics in nonazotemic cirrhotic patients with ascites while it impairs renal function. On the other hand, the addition of midodrine can ameliorate the hyperdynamic circulation without inducing renal dysfunction in these patients.

Rifaximin Improves Systemic Hemodynamics and Renal Function in Patients With Alcohol-Related Cirrhosis and Ascites

Circulating levels of endotoxin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α increase with intestinal bacterial overgrowth and translocation, and are believed to be involved in the pathogenesis of hyperdynamic circulatory syndrome and functional renal failure in patients with advanced cirrhosis. We investigated the effects of the antibiotic rifaximin on systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites. We measured mean arterial pressure, cardiac output (CO) by Doppler ultrasound, systemic vascular resistance (as the ratio of mean arterial pressure:CO), plasma renin activity, levels of plasma aldosterone, the glomerular filtration rate by plasma clearance of technetium-99m-DTPA, natriuresis, levels of plasma endotoxin, and serum levels of IL-6 and TNF-α in 13 patients at baseline and after 4 weeks of treatment with rifaximin. Rifaximin treatment significantly reduced CO and significantly increased systemic vascular resistance, in association with a significant decrease in plasma rennin activity. The therapy also significantly increased the glomerular filtration rate and natriuresis while reducing levels of endotoxin, IL-6, and TNF-α. Intestinal decontamination with rifaximin improved systemic hemodynamics and renal function in patients with advanced cirrhosis.

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.

Evaluation of meningioma aggressiveness by 99mTc-Tetrofosmin SPECT

OBJECTIVES Although meningiomas usually have a benign clinical course, atypical and malignant types of this brain tumor are associated with high recurrence rates and poor outcome; thus, DNA ploidy and S-phase -- as determined by DNA flow cytometry -- are useful indicators of their biological behavior. Brain single-photon emission computed tomography (SPECT) has been suggested as a potentially useful modality for the metabolic assessment of various brain tumors. This study evaluated whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake correlates with meningioma proliferative activity, as assessed by flow cytometry analysis. PATIENTS AND METHODS Ten consecutive patients (3 males, 7 females, mean age 64.6 years) with a diagnosis of a symptomatic intracranial meningioma, planned to undergo surgery, were studied. Brain SPECT by (99m)Tc-TF was performed within a week prior to surgical excision and flow cytometric analysis was performed in the excised tissue. Tumoral radiotracer accumulation was first assessed visually. Semiquantitative image analysis was also performed, by calculating the lesion-to-normal (L/N) uptake ratio. RESULTS Benign meningiomas were diagnosed in 8/10 cases, the remaining 2/10 patients had anaplastic lesions. DNA aneuploidy was found in 2 lesions, the remaining tumors were diploid. There was a significant correlation between tracer uptake and the percentage of the cell fraction on S-phase (r=0.733, P=0.05). There was also a positive correlation between tracer uptake and the level of aneuploidy and tumor grade. CONCLUSION These results imply that (99m)Tc-TF brain SPECT may have the ability to discriminate benign meningiomas from malignant meningiomas pre-operatively, the tracer uptake being a likely indicator of their proliferative activity.

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.

Evaluation of glioma proliferation by 99mTc-Tetrofosmin

The proliferation potential of gliomas is an indicator of their aggressiveness with significant implications in patient management and prognosis, but its assessment requires tissue sampling.1 We evaluated the relationship between glioma proliferation (as expressed by the Ki-67 index) and the uptake of the tumor-seeking radiotracer technetium-99m Tetrofosmin (99mTc-TF). Fourteen patients with a space-occupying lesion suspicious for glioma on structural brain imaging were prospectively enrolled. Scintitomographic (SPECT) imaging was performed and within a week the lesion was removed surgically; Ki-67 was assessed in the excised specimens by MIB-1 immunostaining. Three patients were excluded from the study because their lesions were proven metastatic. In the 11 patients eligible for analysis (7 males, 4 females; mean age 49.5 ± 7.5 years), the diagnosis was glioblastoma multiforme (6 cases), anaplastic astrocytoma (1), anaplastic oligodendroglioma (2), low-grade oligodendroglioma (1), and low-grade astrocytoma (1). We found a significant positive linear correlation between 99mTc-TF uptake and Ki-67 expression (r = 0.95, p = 0.001 [Spearman rank analysis]; Fig. 1 – 3). No significant correlation was observed between tracer uptake and tumor grade (r = 0.27, p = 0.420). The preliminary results of this pilot study, although deriving from a limited patient sample, propose that this tracer may hold a potential role as a noninvasive marker of glioma proliferative activity. Figure 1 T1-weighted, gadolinium-enchanced MRI (A) in a low-grade oligodendroglioma of the left frontal lobe. Faint 99mTc-Tetrofosmin uptake (B, arrow) correlated with Ki-67 approx. 2% (C; MIB-1 ×100). Figure 3 Correlation between 99mTc-Tetrofosmin uptake (expressed as lesion-to-normal [L/N] uptake ratio) and cellular proliferation rate (MIB-1) in the studied gliomas.

Tc-99m Tetrofosmin SPECT for the differentiation of a cerebellar hemorrhage mimicking a brain metastasis from a renal cell carcinoma

Dear Editor, Distinguishing neoplastic from non-neoplastic intracerebral hemorrhage is a difficult task. We evaluated the usefulness of Tc-99m Tetrofosmin brain SPECT in a patient suspected of having a neoplastic intracerebral hematoma. A 55-year old man was admitted to the hospital for a severe frontal headache of sudden onset. An emergency CT scan was performed and a hemorrhagic lesion was revealed in the left cerebellar hemisphere. The patient was hospitalized for further evaluation and treatment. Two years earlier he had undergone nephrectomy. The histological diagnosis was clear cell carcinoma. MRI brain scan was performed and showed that the lesion was hyperintense on T1 (Figure 1) and T2 weighted images, compressing the fourth ventricle and pons, and surrounded by edema. A ring enhancement was also noted after contrast administration (Figure 2). A metastatic lesion was suspected. For further investigation a brain SPECT was performed using Tc-99m Tetrofosmin. The uptake of Tc-99m Tetrofosmin was assessed visually but no area of abnormal uptake appeared in the region of interest (Figure 3). Due to the patient’s previews renal cell carcinoma the lesion was resected. Histopathologically it was proven to be hemorrhage. In average 1–3 years after nephrectomy, 3, 9–24% of patients with renal cell carcinoma experience brain metastasis [1]. Especially clear cell renal cell carcinoma has the propensity for distant metastasis from the early stage of the disease to several years [2,3]. Furthermore, metastatic brain tumors have the highest incidence of tumoral bleeding [4]. MRI cannot always distinguish between neoplastic and non-neoplastic hemorrhage due to considerable overlap between their imaging findings [5]. Tc-99m Tetrofosmin is a lipophilic diphosphine routinely used for myocardial perfusion imaging. Its whole uptake mechanism is not understood although bearing similarities to Tc-99m MIBI and depending

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.