Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.

BACKGROUND: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma. METHODS: SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2-5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. FINDINGS: Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9-33·6) in the SIRT group and 28·1 months (20·0-35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7-9·9) in the SIRT group versus 9·9 months (8·7-11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94-1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. INTERPRETATION: In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. FUNDING: Sirtex Medical Inc.

(18)F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma.

PURPOSE: To evaluate the performance of (18)F-L-dihydroxyphenylalanine ((18)F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. METHODS: We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone (18)F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. RESULTS: (18)F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of (18)F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. CONCLUSION: (18)F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by (18)F-DOPA PET/CT.

Circulating microparticles bearing Fibrin associated with whole-body 18FDG-PET: diagnostic tools to detect paraneoplastic polymyalgia rheumatica.

Polymyalgia rheumatica (PMR), a chronic inflammatory rheumatism, can be the expression of a paraneoplastic syndrome. The same clinical symptoms are frequently observed at the early stage of the benign and malignant forms. Here, our aim was to develop diagnostic tools to differentiate paraneoplastic PMR from essential PMR. We combined an 18FDG-PET and detection of circulating procoagulant microparticles (MPs), such as fibrin positive (FibMPs), by flow cytometry. Two patients with PMR and a similar profile were selected. In the two patients, the 18FDG-PET revealed a hypermetabolic focus. However, the concentrations of fibrin+/annexin+ microparticles detected were (10 times higher in one of the two patients, who was later found to have breast cancer. The association of 18FDG-PET and the detection of microparticle fibrin positives by flow cytometry allows separating essential PMR (hypermetabolism by 18FDG-PET, low FibMPs) from paraneoplastic PMR.

Rhinal hypometabolism on FDG PET in healthy APO-E4 carriers: impact on memory function and metabolic networks.

PURPOSE: The ε4 allele of the apolipoprotein E (APO-E4) gene, a genetic risk factor for Alzheimer's disease (AD), also modulates brain metabolism and function in healthy subjects. The aim of the present study was to explore cerebral metabolism using FDG PET in healthy APO-E4 carriers by comparing cognitively normal APO-E4 carriers to noncarriers and to assess if patterns of metabolism are correlated with performance on cognitive tasks. Moreover, metabolic connectivity patterns were established in order to assess if the organization of neural networks is influenced by genetic factors. METHODS: Whole-brain PET statistical analysis was performed at voxel-level using SPM8 with a threshold of p < 0.005, corrected for volume, with age, gender and level of education as nuisance variables. Significant hypometabolism between APO-E4 carriers (n = 11) and noncarriers (n = 30) was first determined. Mean metabolic values with clinical/neuropsychological data were extracted at the individual level, and correlations were searched using Spearman's rank test in the whole group. To evaluate metabolic connectivity from metabolic cluster(s) previously identified in the intergroup comparison, voxel-wise interregional correlation analysis (IRCA) was performed between groups of subjects. RESULTS: APO-E4 carriers had reduced metabolism within the left anterior medial temporal lobe (MTL), where neuropathological changes first appear in AD, including the entorhinal and perirhinal cortices. A correlation between metabolism in this area and performance on the DMS48 (delayed matching to sample-48 items) was found, in line with converging evidence involving the perirhinal cortex in object-based memory. Finally, a voxel-wise IRCA revealed stronger metabolic connectivity of the MTL cluster with neocortical frontoparietal regions in carriers than in noncarriers, suggesting compensatory metabolic networks. CONCLUSION: Exploring cerebral metabolism using FDG PET can contribute to a better understanding of the influence of genetic factors on cerebral metabolism at both the local and network levels leading to phenotypical variations of the healthy brain and selective vulnerability.

18F-FDOPA PET/CT imaging of insulinoma revisited.

PURPOSE: (18)F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to (18)F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with (18)F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. METHODS: A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using (18)F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after (18)F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after (18)F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. RESULTS: In the study group, (18)F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All (18)F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted (18)F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final diagnosis was benign insulinoma in four, nesidioblastosis in one, and no definitive diagnosis in the remainder. (18)F-FDOPA PET/CT failed to detect any tumour in these patients. CONCLUSION: According to our experience, CD administration before (18)F-FDOPA injection leads to low residual pancreatic (18)F-FDOPA activity preserving tumoral uptake with consequent insulinoma detection in more than half of adult patients with HH and more than 70 % of patients with a final diagnosis of insulinoma. If (18)F-FDOPA PET/CT is indicated, we strongly recommend combining CD premedication with early acquisition centred over the pancreas.

Distinct patterns of medial temporal impairment in degenerative dementia: a brain SPECT perfusion study in Alzheimer's disease and frontotemporal dementia.

PURPOSE: Medial temporal impairment can be detected clinically and by morphological imaging during Alzheimer's disease (AD), but the existence of a functional impairment in this area seems to be less well established. Yet such functional impairment is classically found in other degenerative cortical dementias, such as the frontal variant of frontotemporal dementia (fv-FTD). The aim of this study was to characterize and compare brain SPECT perfusion of the medial temporal lobe in AD and fv-FTD. METHODS: Voxel-based comparisons were performed using SPM8 between cerebral SPECT images from 85 AD patients, 25 fv-FTD patients and 12 healthy controls at the whole-brain level and the medial temporal lobe level using a region of interest approach (p < 0.001, corrected for the cluster). RESULTS: In the free and cued selective reminding test, used to evaluate medial temporal memory function, AD patients had significantly lower scores than the fv-FTD patients (p < 0.005). AD and fv-FTD patients showed hypoperfused medial temporal structures in comparison to normal controls. However, fv-FTD patients had more pronounced hypoperfusion in this area, with a different topography, more anterior and more parahippocampal. CONCLUSION: These results show that medial temporal hypoperfusion can be detected in degenerative dementias by SPECT. Paradoxically, the hypoperfusion is more severe in fv-FTD than in AD patients, even though the mnesic profile of AD is more altered, suggesting the existence of inefficient compensatory mechanisms.

Diagnostic yield of FDG positron-emission tomography/computed tomography in patients with CEID infection: a pilot study.

AIMS: Whole body imaging with (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) has proven useful in various infectious diseases. The purpose of this pilot study was to assess the diagnostic yield of FDG PET/CT in patients with cardiac implantable electronic device (CIED) infection. METHODS AND RESULTS: A total of 21 patients with CIED infection were prospectively included. Diagnosis of CIED infection was made in accordance with current criteria. It was classified in three categories, i.e. superficial skin infection, pocket site infection, or cardiac device-related infective endocarditis (CDRIE). All patients underwent FDG PET/CT. Scans were interpreted blindly, i.e. without prior knowledge of diagnosis, by experienced nuclear medicine physicians. The accuracy of FDG PET/CT was assessed for each diagnostic category. Findings demonstrated superficial skin infection in 1 patient, pocket site infection in 15, and CDRIE in 13 (definite: 7; possible: 6). In patients with pocket site infection, the sensitivity and specificity of FDG PET/CT were 86.7% [59.5-98.3, 95% confidence interval (CI)] and 100% [42.1-100, 95% CI]. The only patient with superficial skin infection was accurately identified by FDG PET/CT. The sensitivity and specificity of FDG PET/CT in patients with CDRIE were 30.8% [9.1-61.4, 95% CI] and 62.5% [24.5-91.5, 95% CI]. Most false-negative results occurred in patients who had undergone previous antimicrobial treatment. CONCLUSION: This study indicates that FDG PET/CT is highly accurate for the diagnosis of skin and pocket CIED infection but low for infective endocarditis. This suggests that the reliability of FDG PET/CT findings in management decision making varies according to the type of CIED infection.

Cognitive and metabolic correlates of emotional vulnerability in patients with temporal lobe epilepsy.

BACKGROUND: Recent investigations have suggested that the occurrence of epileptic seizures is not completely random. In particular, various types of psychological changes or life events may act as triggering factors. OBJECTIVE: To identify a possible link between self-perception of the impact of affective precipitants, cognitive responses modulated by aversive information and brain metabolic modifications in patients with temporal lobe epilepsy (TLE). METHODS: The extent to which seizures were elicited or not by emotional precipitants was estimated using a self-reported scale, allowing distinction of two groups: 'Emo-TLE' group (patients reporting to have seizures triggered by emotional events) and 'Other-TLE' group, which were compared with healthy individuals ('control' group). Attentional biases were investigated using the probe detection paradigm, using negative and neutral stimuli. Interictal brain metabolism was studied using FDG-PET, and comparison was made between controls, Emo-TLE and Other-TLE groups. RESULTS: Patients with emotional vulnerability (Emo-TLE) disclosed specific attentional biases towards negative stimuli compared with the Other-TLE and control groups. Patients with Emo-TLE also exhibited specific hypometabolism in the anterior temporal lobe, including amygdala and hippocampus. The degree of attentional biases correlated with decreased metabolism in these regions. CONCLUSIONS: This investigation shows that the impact of affective events is the result of self-perception and also that it might be determined by specific cognitive and brain metabolic modifications in TLE.

Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects.

PURPOSE: Several studies have shown age- and gender-related differences in striatal dopamine transporter (DaT) binding. These studies were based on a striatal region on interest approach that may have underestimated these effects and could not evaluate extrastriatal regions. Our aim was to determine the effects at the voxel level of age and gender on whole-brain DaT distribution using [(123)I]FP-CIT SPECT in healthy subjects. METHODS: We performed a whole-brain [(123)I]FP-CIT SPECT voxel-based analysis using SPM8 and a standardized normalization template (p < 0.05, corrected using the false discovery rate method) in 51 healthy subjects aged from 21 to 79 years. RESULTS: We found an age-related DaT binding decrease in the striatum, anterior cingulate/medial frontal cortices and insulo-opercular cortices. Also DaT binding ratios were higher in women than men in the striatum and opercular cortices. CONCLUSION: This study showed both striatal and extrastriatal age-related and gender-related differences in DaT binding in healthy subjects using a whole-brain voxel-based non-a priori approach. These differences highlight the need for careful age and gender matching in DaT analyses of neuropsychiatric disorders.

Independent prognostic value of pre-treatment 18-FDG-PET in high-grade gliomas.

The prognostic value of PET with (18F)-fluoro-2-deoxy-D: -glucose (FDG) has been shown in high-grade gliomas (HGG), but not compared with consensual prognostic factors. We sought to evaluate the independent predictive value of pre-treatment FDG-PET on overall (OS) and event-free survival (EFS). We retrospectively analyzed 41 patients with histologically-confirmed HGG (31 glioblastomas and 10 anaplastic gliomas). The pre-treatment uptake of FDG was assessed qualitatively by five-step visual metabolic grading, and quantitatively by the ratio between the tumor and contralateral maximal standardized uptake value (T/CL). EFS and OS following PET were compared with FDG uptake by univariate analysis, and by two multivariate analyses: one including main consensual prognostic factors (age, KPS, extent of surgery and histological grade), and the other including the classification system of the Radiation Therapy Oncology Group (Recursive Partitioning Analysis, RPA). Median OS and EFS were 13.8 and 7.4 months, respectively, for glioblastomas, and over 25.8 and 12 months, respectively, for anaplastic gliomas (P = 0.040 and P = 0.027). The T/CL ratio predicted OS in the entire group [P = 0.003; Hazard Ratio (HR) = 2.3] and in the glioblastoma subgroup (P = 0.018; HR = 2), independently of age, Karnofsky performance status, histological grade, and surgery, and independently of RPA classification. T/CL ratio tended to predict EFS in the whole group (P = 0.052). The prognostic value of visual metabolic grade on OS was less significant than T/CL ratio, both in the entire group and in the glioblastoma subgroup (P = 0.077 and P = 0.059). Quantitative evaluation of the ratio between the maximal tumor and contralateral uptake in pre-treatment FDG-PET provides significant additional prognostic information in newly-diagnosed HGG, independently of consensual prognostic factors.

Schizophrenia with preserved insight is associated with increased perfusion of the precuneus.

BACKGROUND: Preserved insight into illness has been suggested to be predictive of outcome in patients with schizophrenia. We aimed to investigate the functional substrate underlying preserved insight in these patients. METHODS: We recruited patients with paranoid schizophrenia and healthy controls matched for age and sex. Patients were grouped according to preserved or impaired insight into illness using the Scale to assess Unawareness of Mental Disorder (SUMD). Whole-brain technetium-99m ethyl cysteinate dimer single photon emission computed tomography regional cerebral blood flow was compared at the voxel level between the 2 groups using a statistical parametric map (voxel-level significance of p < 0.001, uncorrected; cluster level significance of p < 0.05, uncorrected). RESULTS: We enrolled 31 right-handed patients with schizophrenia and 18 controls in our study. Twenty-one (67.7%) patients had preserved insight. The 2 groups did not differ significantly in demographic and clinical characteristics or in treatment. Compared with controls, the whole group of patients showed bilateral frontotemporal hypoperfusions, with no statistical difference between patients with preserved or impaired insight for these areas. Patients with preserved insight showed significantly increased perfusion of the bilateral precuneus relative to those with impaired insight. LIMITATIONS: Patients with subtypes other than paranoid schizophrenia have to be investigated to assess whether involvement of the precuneus in patients with preserved insight can be identified across the full spectrum of subtypes and symptoms of schizophrenia. Moreover, our study concerned only the central dimension (awareness of mental disorder) of 1 scale (SUMD); other dimensions of insight could be studied. CONCLUSION: Our results show that schizophrenia with preserved insight is associated with greater perfusion of the precuneus, a brain area known to be involved in self- consciousness, suggesting a compensatory mechanism of fronto-temporal impairment.

Functional involvement of superior temporal sulcus in quality of life of patients with schizophrenia.

The aim of this study was to investigate the neural substrate underlying quality of life (QoL) in patients with schizophrenia. Thirty-one right-handed patients were included. Patients were grouped according to 'high' and 'low' QoL levels. Whole-brain single photon emission computed tomography (SPECT) with (99m)Tc-labeled ethylcysteinate dimer ((99m)Tc-ECD), for the measurement of voxel-based regional cerebral blood flow (rCBF), was used to compare these two groups with Statistical Parametric Mapping. Correlations of rCBF with QoL scores were secondarily explored. Nineteen of the 31 patients had a high QoL level. There was no significant difference in demographic and clinical characteristics between patients with high and low QoL levels. In comparison to patients with low QoL, those with high QoL exhibited significant bilateral temporal hypoperfusions, primarily in the superior temporal sulcus (STS). In the total group of patients, perfusion in the left STS was negatively correlated with psychological well-being, self-esteem, and sentimental life, as well as with the global index of the questionnaire. This study shows that perfusion of the STS, a brain area thought to contribute to self/other awareness and metacognition, is involved in the functional substrate underlying QoL. Our findings contribute to clarifying the scientific foundation required for a better clinical use of QoL questionnaires by suggesting that the recognition of illness-related impairment is associated with alteration of QoL.

Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression.

PURPOSE: The aim of this study was to determine the predictive value of whole-brain voxel-based regional cerebral blood flow (rCBF) for repetitive transcranial magnetic stimulation (rTMS) response in patients with pharmacoresistant depression. METHODS: Thirty-three right-handed patients who met DSM-IV criteria for major depressive disorder (unipolar or bipolar depression) were included before rTMS. rTMS response was defined as at least 50% reduction in the baseline Beck Depression Inventory scores. The predictive value of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) for rTMS response was studied before treatment by comparing rTMS responders to non-responders at voxel level using Statistical Parametric Mapping (SPM) (p < 0.001, uncorrected). RESULTS: Of the patients, 18 (54.5%) were responders to rTMS and 15 were non-responders (45.5%). There were no statistically significant differences in demographic and clinical characteristics (p > 0.10). In comparison to responders, non-responders showed significant hypoperfusions (p < 0.001, uncorrected) in the left medial and bilateral superior frontal cortices (BA10), the left uncus/parahippocampal cortex (BA20/BA35) and the right thalamus. The area under the curve for the combination of SPECT clusters to predict rTMS response was 0.89 (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value for the combination of clusters were: 94, 73, 81 and 92%, respectively. CONCLUSION: This study shows that, in pharmacoresistant depression, pretreatment rCBF of specific brain regions is a strong predictor for response to rTMS in patients with homogeneous demographic/clinical features.

Heath-related quality of life in thyroid cancer patients following radioiodine ablation.

BACKGROUND: There is limited information about the medium to long-term health-related quality of life (QOL) in thyroid cancer patients after initial therapy and the existing studies suffer from limitations. The aim of the study was to assess the determinants of medium-term QOL after the initial therapy. METHODS: Following a total thyroidectomy, 88 thyroid cancer patients received either rhTSH or hypothyroid-assisted radioiodine ablation (RRA) using 3.7 GBq (100 mCi) of radioiodine. QOL evaluation of the patients using the validated Functional Assessment of Chronic Illness & Therapy (FACIT) was performed at the time of inclusion (t0) and later at the 9-month post-RRA (t1). RESULTS: 83 patients were eligible for the final evaluation. Medium-term FACIT scores were not statistically different between t0 and t1 patients. All but one domain of the QOL score was similar between t0 and t1. Using a multivariate analysis, only age and immediate postoperative QOL scores were found to be determinants of the overall medium term 9-month QOL scores. Analysis showed that 'high QOL levels' (baseline and 9-month) and 'no depression', 'low anxiety levels', were associated with '<45 yrs', 'men', 'partner', and 'rhTSH stimulation'. CONCLUSIONS: The use of radioiodine ablation does not seem to affect the medium term QOL scores of patients. Medium-term QOL is mainly determined by pre-ablation QOL. The assessment of baseline QOL might be interesting to evaluate in order to adapt the treatment protocols, the preventive strategies, and medical information to patients for potentially improving their outcomes.

Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study.

BACKGROUND: A surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence. AIMS: To assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up. METHODS: A multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT. RESULTS: A total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038). CONCLUSIONS: PET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.

Reading epilepsy from the dominant temporo-occipital region.

BACKGROUND: Reading epilepsy is a rare form of epilepsy, classified among idiopathic, age- and localisation-related (partial) epilepsies as a reflex epilepsy syndrome. Seizures usually consist of myoclonic jerks restricted to the jaw. However, distinct ictal features including visual symptoms and paroxysmal a- or dyslexia are described in some patients. The anatomical substrate of ictogenesis in reading epilepsy remains poorly understood. METHODS: The authors report here the case of a primary reading epilepsy for which ictal semiology was characterised by visual symptoms and dyslexia, investigated by MRI, interictal high-resolution EEG and PET, ictal video-EEG and SPECT. Brain MRI was normal. Interictal high-resolution EEG was performed with 64 scalp channels, a realistic head model and different algorithms to solve the inverse problem. RESULTS: Interictal source localisations highlighted the left occipito-temporal junction. Interictal PET demonstrated bilateral occipito-temporal hypometabolism with left-sided predominance. Ictal EEG showed a rhythmic discharge in left temporo-parieto-occipital junction channels, with left occipito-temporal predominance. MRI fusion of the coregistered subtraction between ictal and interictal SPECT individualised relative hyperperfusion affecting (a) the left occipito-parietal junction area, (b) the left lateral middle and inferior temporal gyri and (c) the left inferior frontal area. CONCLUSION: Besides reading-induced myoclonic jerks of the jaw, a second variant of reading epilepsy exists with clearly partial seizures manifested by visual symptoms and a- or dyslexia. These seizures originate from the occipito-temporal region of the dominant hemisphere, corresponding to the posterior part of the neural network that underlies the function of reading.

Partially reversible cortical metabolic dysfunction in familial hemiplegic migraine with prolonged aura.

We report a SPECT and PET voxel-based analysis of cerebral blood flow and metabolic rate for glucose in a 23-year-old woman with familial hemiplegic migraine (FHM) caused by ATP1A2 gene mutation. In comparison with healthy subjects, a PET scan showed brain glucose hypometabolism, controlaterally to the hemiplegia, in the perisylvian area early in the attack (Day 1), without any SPECT perfusion abnormalities. Decrease in metabolic rate was only partially reversible at Day 78, concordant at this time with a remaining hemisensory loss. These findings provide further evidence for a primary cortical metabolic dysfunction in FHM.

Brain regions underlying word finding difficulties in temporal lobe epilepsy.

Word finding difficulties are often reported by epileptic patients with seizures originating from the language dominant cerebral hemisphere, for example, in temporal lobe epilepsy. Evidence regarding the brain regions underlying this deficit comes from studies of peri-operative electro-cortical stimulation, as well as post-surgical performance. This evidence has highlighted a role for the anterior part of the dominant temporal lobe in oral word production. These conclusions contrast with findings from activation studies involving healthy speakers or acute ischaemic stroke patients, where the region most directly related to word retrieval appears to be the posterior part of the left temporal lobe. To clarify the neural basis of word retrieval in temporal lobe epilepsy, we tested forty-three drug-resistant temporal lobe epilepsy patients (28 left, 15 right). Comprehensive neuropsychological and language assessments were performed. Single spoken word production was elicited with picture or definition stimuli. Detailed analysis allowed the distinction of impaired word retrieval from other possible causes of naming failure. Finally, the neural substrate of the deficit was assessed by correlating word retrieval performance and resting-state brain metabolism in 18 fluoro-2-deoxy-d-glucose-Positron Emission Tomography. Naming difficulties often resulted from genuine word retrieval failures (anomic states), both in picture and in definition tasks. Left temporal lobe epilepsy patients showed considerably worse performance than right temporal lobe epilepsy patients. Performance was poorer in the definition than in the picture task. Across patients and the left temporal lobe epilepsy subgroup, frequency of anomic state was negatively correlated with resting-state brain metabolism in left posterior and basal temporal regions (Brodmann's area 20-37-39). These results show the involvement of posterior temporal regions, within a larger antero-posterior-basal temporal network, in the specific process of word retrieval in temporal lobe epilepsy. A tentative explanation for these findings is that epilepsy induces functional deafferentation between anterior temporal structures devoted to semantic processing and neocortical posterior temporal structures devoted to lexical processing.

18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?

UNLABELLED: Our objective was to evaluate (18)F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. METHODS: Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). (18)F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. RESULTS: All but 2 patients showed significantly increased (18)F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean +/- SD, 8.2 +/- 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean +/- SD, 9.7 +/- 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase-related tumors were notable in being the most (18)F-FDG-avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). (18)F-FDG PET was superior to (131)I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, (18)F-FDG PET underestimated the extent of the disease, compared with 6-(18)F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain (18)F-FDG uptake since most tumors were highly avid for (18)F-FDG. CONCLUSION: (18)F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation?

PURPOSE: Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. METHODS: We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. RESULTS: Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. CONCLUSION: These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the "net sum" of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective.