Olivier Mundler

Etiologic diagnosis of 204 pericardial effusions.

The etiologic evaluation of pericardial effusion is frequently unsuccessful when noninvasive methods are used. To determine the cause of the current episode, all patients with echographically identified pericardial effusion from May 1998 to December 2002 underwent noninvasive diagnostic testing of blood, throat, and stool samples. Patients with postpericardiotomy syndrome were excluded. To analyze the value of our tests, we tested randomly selected blood donors as negative controls.Among 204 included patients, 107 (52.4%) had a final etiologic diagnosis: the etiology of 52 was highly suspected at first examination and later confirmed (thyroid deficiency, 5 cases; systemic lupus erythematous, 7; rheumatoid arthritis, 7; scleroderma, 3; cancer, 25; and renal insufficiency, 5). A definite etiologic diagnosis was made in 11 patients from pericardial fluid analysis (cancer, 5 cases; tuberculosis, 3; Streptococcus pneumoniae, Citrobacter freundii, and Actinomyces, 1 case each). Among 141 patients considered to have idiopathic pericarditis, 44 (32.1%) gained an etiologic diagnosis by our systematic testing strategy. This included serologic evaluation of serum (Coxiella burnetii, 10 cases; Bartonella quintana, 1; Legionella pneumophila, 1; Mycoplasma pneumoniae, 4; influenza virus, 1), viral culture of throat swabs (enterovirus, 8 cases; and adenovirus, 1), high-level antinuclear antibodies (>1/400, 3 cases), and thyroid-stimulating hormone (15 abnormal results). Antibodies to Toxoplasma and cytomegalovirus, enterovirus recovered from rectal swabs, and low-level antinuclear antibodies were seen with equal frequency in patients and controls.Using our evaluation strategy, the number of pericardial effusions classified as idiopathic was less than in other series. Systematic testing for Q fever, Mycoplasma pneumoniae, thyroid abnormalities, and antinuclear antibodies, accompanied by viral throat cultures, frequently enabled us to diagnose diseases not initially suspected in patients with pericardial effusion.

18F-FDG Avidity of Pheochromocytomas and Paragangliomas: A New Molecular Imaging Signature?

Our objective was to evaluate 18F-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). 18F-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 18F-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 18F-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). 18F-FDG PET was superior to 131I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, 18F-FDG PET underestimated the extent of the disease, compared with 6-18F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain 18F-FDG uptake since most tumors were highly avid for 18F-FDG. Conclusion: 18F-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.

Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study

Background  Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low‐risk thyroid cancer patients.

The role of 18F‐FDOPA and 18F‐FDG–PET in the management of malignant and multifocal phaeochromocytomas

Background  18F‐DOPA has emerged as a promising tool in the localization of chromaffin‐tissue‐derived tumours. Interestingly, phaeochromocytomas (PHEO) are also FDG avid.

Limited Value of 18F-F-DOPA PET to Localize Pancreatic Insulin-Secreting Tumors in Adults with Hyperinsulinemic Hypoglycemia

CONTEXT Fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-FDOPA PET) imaging is increasingly used in the workup of neuroendocrine tumors. It has been shown to be an accurate tool in the diagnosis of congenital hyperinsulinism, but limited information is available on its value in adult disease. OBJECTIVE, PATIENTS, AND DESIGN: The objective of this study was to review our experience with 18F-FDOPA PET imaging in six consecutive patients with hyperinsulinemic hypoglycemia (HH) (four solitary insulinomas, one diffuse beta-cell hyperplasia, one malignant insulinoma). 18F-FDOPA uptake was also evaluated in 37 patients (43 procedures) without HH or other pancreatic neuroendocrine tumors, which acted as a control group. RESULTS Using visual analysis, 18F-FDOPA-PET proved positive in only one case (a multiple endocrine neoplasia type 1 related insulinoma). In diffuse beta-cell hyperplasia, the pancreatic uptake was similar to controls. In the patient with liver metastases, the extent of disease was underestimated. The pancreatic uptake was not statistically different between controls and hyperinsulinemic patients. The main limitation for identifying insulinomas or beta-cell hyperplasia in adults appears to be to the 18F-FDOPA uptake and retention in the whole pancreas. This drawback is potentially circumvented in focal hyperplasia in newborns due to a lower aromatic amino acid decarboxylase expression in the extralesional pancreatic parenchyma. CONCLUSIONS 18F-FDOPA PET is of limited value in localizing pancreatic insulin secreting tumors in adult HH. Our results contrast with the referential study and require further analysis.

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 (Brodmanns 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.

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

PurposeThe 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.MethodsThirty-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 99mTc-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).ResultsOf 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.ConclusionThis 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.

FDG-PET predicts survival in recurrent high-grade gliomas treated with bevacizumab and irinotecan

Prognosis of recurrent high-grade glioma (HGG) is poor, although bevacizumab has been documented in that context. This study aimed to determine the independent prognostic value of fluorodeoxyglucose (FDG)-PET on progression-free survival (PFS) and overall survival (OS) of recurrent HGG after combined treatment with bevacizumab and irinotecan, compared with other documented prognostic variables. Twenty-five adult patients with histologically proven HGG were included at recurrence. Brain FDG-PET imaging was performed within 6 weeks of starting chemotherapy with bevacizumab and irinotecan. Response based on MRI was assessed every 2 months according to revised assessment in Neuro-Oncology (RANO) criteria. Median PFS and OS were 4 months (range, 0.9-10.4 months) and 7.2 months (range, 1.2-41.7 months), respectively. At 6 months, PFS and OS rate were 16.0% and 72.0%. FDG uptake was the most powerful predictor of both PFS and OS, using either univariate or multivariate analysis, among all variables tested: histological grade, Karnofsky performance status, steroid intake, and number of previous treatments. Moreover, FDG uptake was also prognostic of response to bevacizumab-based therapy. This study provides the first evidence that pretreatment FDG-PET can serve as an imaging biomarker in recurrent HGG for predicting survival following anti-angiogenic therapy with bevacizumab.

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.

A Pilot Study Comparing Furosemide and Hydrochlorothiazide in Patients With Hypertension and Stage 4 or 5 Chronic Kidney Disease

Furosemide is the diuretic of choice for the treatment of hypertension in chronic kidney disease but the adaptative changes in the distal nephron may decrease its efficacy. Hydrochlorothiazide is not believed to be efficient in this setting. In a randomized, double‐blind, cross‐over trial, 23 patients with hypertension and stage 4 or 5 chronic kidney disease received long‐acting furosemide (60 mg) and hydrochlorothiazide (25 mg) for 3 months and then both diuretics for 3 months. Sodium and chloride fractional excretions were measured after 3 months of each diuretic and then after their association. A trend towards an increase in the fractional excretion of sodium and chloride was observed with furosemide and hydrochlorothiazide (P=not significant). The association of the two diuretics increased the fractional excretions of sodium and chloride from 3.4±1.8 to 4.9±2.8 and from 3.8±2.0 to 6.0±3.1, respectively (P<.05). Furosemide and hydrochlorothiazide decreased mean blood pressure by the same extent. The association of the two diuretics was more efficient on blood pressure. There were no differences between furosemide and hydrochlorothiazide with respect to natriuresis and blood pressure control in patients with hypertension and chronic kidney disease.