Jean-Pierre Willi

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

Osteonecrosis of the jaw (ONJ) can be associated with nitrogen-containing bisphosphonates (NBPs) therapy. Various mechanisms of NBP-associated ONJ have been proposed and there is currently no consensus of the underlying pathogenesis. The detailed medical and dental histories of 30 ONJ patients treated with NBPs for malignant diseases (24) or osteoporosis (6) were analyzed. The necrotic bone was resected and analyzed histologically after demineralization. In 10 patients the perinecrotic bone was also resected and processed without demineralization. Alveolar bone samples from 5 healthy patients were used as controls. In 14 ONJ patients, serial technetium-99m-methylene diphosphonate scintigraphic scans were also available and confronted to the other data. Strong radionuclide uptake was detected in some patients several months before clinical diagnosis of ONJ. The medullary spaces of the necrotic bone were filled with bacterial aggregates. In the perinecrotic bone, the bacteria-free bone marrow characteristically showed an inflammatory reaction. The number of medullary inflammatory cells taken as an index of inflammation allowed us to discriminate two inflammation grades in the ONJ samples. Low-grade inflammation, characterized by marrow fibrosis and low inflammatory cells infiltration, increased numbers of TRAP(+) mono- and multineacleated cells was seen in patients with bone exposure<2 cm(2). High-grade inflammation, associated with larger lesions, showed amounts of tartrate-resistant acid phosphatase(+)/calcitonin receptor(-) mono- and multinucleated cells, osteocyte apoptosis, hypervascularization and high inflammatory cell infiltration. The clinical extent of ONJ was statistically linked to the numbers of inflammatory cell. Taken together these data suggest that bone necrosis precedes clinical onset and is an inflammation-associated process. We hypothesize that from an initial focus, bone damage spreads centrifugally, both deeper into the jaw and towards the mucosa before the oral bone exposure and the clinical diagnosis of ONJ.

Value of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography in detection and presurgical assessment of pancreatic cancer: A prospective study

Background and Aim:  Positron Emission Tomography (PET) using 18F‐fluorodeoxyglucose (FDG) associated with computed tomography (CT) is increasingly used for the detection and the staging of pancreatic cancer, but data regarding its clinical added value in pre‐surgical planning is still lacking. The aim of this study is to investigate the performance of FDG PET associated with contrast‐enhanced CT in detection of pancreatic cancer.

Longitudinal Analyses of Renal Lesions Due to Acute Pyelonephritis in Children and Their Impact on Renal Growth

PURPOSE Acute pyelonephritis is a common condition in children, and can lead to renal scarring. The aim of this study was to analyze the progression of renal scarring with time and its impact on renal growth. MATERIALS AND METHODS A total of 50 children who had renal scarring on dimercapto-succinic acid scan 6 months after acute pyelonephritis underwent a repeat scan 3 years later. Lesion changes were evaluated by 3 blinded observers, and were classified as no change, partial resolution or complete disappearance. Renal size at time of acute pyelonephritis and after 3 years was obtained by ultrasound, and renal growth was assessed comparing z-score for age between the 2 measures. Robust linear regression was used to identify determinants of renal growth. RESULTS At 6 months after acute pyelonephritis 88 scars were observed in 100 renal units. No change was observed in 27%, partial resolution in 63% and complete disappearance in 9% of lesions. Overall, 72% of lesions improved. Increased number of scars was associated with high grade vesicoureteral reflux (p = 0.02). Multivariate analysis showed that the number of scars was the most important parameter leading to decreased renal growth (CI -1.05 to -0.35, p <0.001), and with 3 or more scars this finding was highly significant on univariate analysis (-1.59, CI -2.10 to -1.09, p <0.0001). CONCLUSIONS Even 6 months after acute pyelonephritis 72% of dimercapto-succinic acid defects improved, demonstrating that some of the lesions may be not definitive. The number of scars was significantly associated with loss of renal growth at 3 years.

18FDG-PET-CT: An Imaging Biomarker of High-Risk Carotid Plaques. Correlation to Symptoms and Microembolic Signals

Background and Purpose— We investigated whether uptake of 18fluoro-2-deoxy-d-glucose (18FDG) positron emission tomography–computed tomography (PET-CT) correlated to clinical symptoms and presence of microembolic signals (MES) detected by transcranial Doppler in patients with carotid stenosis. Methods— 18FDG-PET-CT and MES detection was performed in consecutive patients with 50% to 99% symptomatic or asymptomatic carotid stenoses. Uptake index was defined by a target to background ratio (TBR) between maximum standardized uptake value of the carotid plaque and the mean standardized uptake value of the jugular veins. End points for analysis were presence of symptoms and presence of MES. Results— We included 123 stenosis derived from 110 patients, 60 symptomatic and 63 asymptomatic. MES positive (+) lesions were found in 16%. TBR values were higher in symptomatic compared with asymptomatic (median 2.07 versus 1.78; P<0.0018) and in MES+ compared with MES− plaques (median 2.14 versus 1.86; P<0.008). TBR values were also higher in asymptomatic MES+ compared with MES− plaques (median 1.97 versus 1.76; P<0.03). The best TBR threshold value for symptomatic versus asymptomatic, for MES+ versus MES−, for symptomatic MES+ versus symptomatic or asymptomatic MES−, and for asymptomatic MES+ versus asymptomatic MES− plaques was 1.9. Sensitivity/specificity were, respectively, 56/77%, 73/63%, 79/64%, and 80/77%. We found a strong correlation between number of MES and TBR values (&rgr; 0.26; P=0.0043). Conclusions— 18FDG-PET-CT accurately detected high-risk carotid plaques. Also given its strong correlation to MES, 18FDG-PET-CT may be a useful tool in clinical practice.

The selective amobarbital test in the anterior choroidal artery: Perfusion pattern assessed by intraarterial SPECT and prediction of postoperative verbal memory

To screen for patients at risk for memory decline after temporal lobe epilepsy (TLE) surgery, selective amobarbital procedures, such as injection into the anterior choroidal artery (ACA-IAT), are sometimes used. We investigated the extent of the territory affected during ACA-IAT and its predictive value with respect to postoperative memory. Seventeen patients with TLE underwent ACA-IAT. In 9 of 17 patients, intraarterial SPECT co-registrated to MRI allowed delineation of amobarbital-perfused structures. Another subgroup of 9 of 17 patients underwent anterior temporal lobectomy. Verbal memory was tested pre- and postoperatively and during ACA-IAT. Major variations in the ACA-IAT perfusion pattern occurred and were not correlated with the verbal memory scores during ACA-IAT. Postoperatively, no patient experienced a severe verbal memory decline, but individual postoperative performance was not correlated with results during ACA-IAT. Our study suggests that ACA-IAT can be used to screen for severe postoperative amnesia in inconclusive cases, but cannot predict individual outcome, even when the perfusion pattern is taken into account.

Neuroimaging of the vulnerable plaque

Plaque vulnerability due to inflammation has been shown to be a participating factor in the degenerative process in the arterial wall that contributes to stenosis and embolism. This is believed to have an important role to play also in the genesis of stroke or cerebrovascular diseases. In order to appropriately screen patients for treatment, there is an absolute need to directly or indirectly visualize both the normal carotid and the suspected plaque. This can be done with a variety of techniques ranging from ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI). In addition to angiographic techniques, direct imaging of the plaque can be done either by ultrasound or by the so-called molecular imaging techniques, i.e. positron emission tomography (PET). These findings, together with other clinical and paraclinical parameters should finally guide the therapeutic choice.

Treatment with levetiracetam in a patient with pervasive developmental disorders, severe intellectual disability, self-injurious behavior, and seizures: A case report

Pervasive developmental disorder is characterized by various symptoms that often include self-injurious behavior (SIB). Episodes of SIB occur in the context of high emotional arousal, anger, or fear and may be related to epilepsy. We report the case of a 20-year-old man with pervasive developmental disorder presenting with SIB non-responsive to antipsychotic medication. Positron emission tomography showed a right temporoparietal hypometabolic focal lesion suggestive of an epileptic focus. Two weeks after initiation of levetiracetam (Keppra®), SIB disappeared, without recurrence 24 months later. Levetiracetam (Keppra®) may be beneficial for such patients.

Scintigraphic Identification of Gastric Tissue in a Mediastinal Mass.

We present a Tc pertechnetate scintigraphy performed in a 64-year-old woman to investigate a mediastinal cystic mass in search of residual gastric mucosa after gastrectomy. She had a history of esophagectomy and gastric pull-up for esophageal cancer. Postoperative leakage necessitated ablation of the gastric pull-up and reconstruction using part of the colon. Oral realimentation resulted in mediastinal pain and brownish discharge within the trachea, raising the suspicion of residual gastric pouch. SPECT/CT demonstrated increased tracer uptake in the median part of the mediastinal cyst, and a biopsy confirmed the presence gastric mucosa.