Reliable Detection of Intrapulmonary Shunts Using Contrast-Enhanced Echocardiography in Children With Portal Hypertension or Portosystemic Shunt.

OBJECTIVES: The aim of this study was to analyze if contrast-enhanced echocardiography (CEE) is as reliable as lung perfusion scintigraphy (LPS) to detect intrapulmonary shunting (IPS) in children with portal hypertension (PHTN) or congenital/surgical portosystemic shunts (PSS) and to define the number of cardiac cycles required to exclude intrapulmonary shunting. METHODS: Inclusion criteria for this cross-sectional study were: (1) presence of PHTN or PSS diagnosed on abdominal ultrasound, (2) technically valid saline contrast echocardiography, (3) lung perfusion scintigraphy within 6 months of CEE. The number of cardiac cycles between right atrial opacification and the arrival of contrast in the left atrium were counted. We analyzed our CEE data at three and five cardiac cycles and compared them with LPS results. RESULTS: The study population was composed of 78 children (38 girls, 49%) ages 2.1-18.8 years (mean 9.8). Sixty-nine patients had PHTN (88%), and nine had a PSS (11%). Eleven subjects (14%) presented evidence of IPS on LPS. Peripheral oxygen saturation was lower in the subjects with IPS detected on LPS (95.3 ±â€Š1.7% vs 99.0 ±â€Š1.4%; P < 0.01). Comparison of LPS with CEE before three and five cardiac cycles showed that CEE is highly specific (95.7%) as early as three cardiac cycles with markedly better sensitivity (72.7%) when using five cardiac cycles. Furthermore, a negative study using five cardiac cycles ruled out IPS with a 95% negative predictive value. The cardiac cycle at which the bubbles appeared in the left atrium was inversely correlated to the shunt index measured using LPS (r = -0.563; P = 0.001). CONCLUSION: CEE is sufficient for the screening of IPS in children with PHTN or congenital/surgical PSS, obviating the need for LPS.

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 (18)fluoro-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 (ρ 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.

[Opening of the Geneva University Hospital Prostate Cancer Center]. / Création du Centre du cancer de la prostate des HUG.

In 2014, Geneva University Hospital has opened the first certified prostate cancer Center of western Switzerland. It incorporates 29 entities implicated in the diagnosis and treatment of this disease, thereby assuring that all available ressources are made available to patients, regardless of the division to which they were initially referred. The main strength of the Center lies in the synergy generated by its multidisciplinary tumor board. Furthermore, regular conferences, staff meetings, propectively held registers and the yearly re-certification audit support its constant quality improvement.

Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide.

PURPOSE: The biokinetics and dosimetry of (111)In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and (111)In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients. METHODS: Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15 MBq) was performed 16 ± 5 days before the NOCATE scan (108 ± 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. RESULTS: Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar α and ß half-lives, but the ß fraction of NOCATE was double that of OCTREO. Blood T (1/2)ß for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 µSv/MBq) exceeded that of OCTREO (52 µSv/MBq), and the latter result was similar to the ICRP 106 value of 54 µSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components. CONCLUSION: NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.

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 (18)F-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. METHODS: We prospectively evaluated FDG PET/CT studies obtained in patients with suspicion of operable pancreatic cancer between May 2006 and January 2008. Staging was conducted according to a standardized protocol, and findings were confirmed in all patients by surgical resection or biopsy examination. RESULTS: Forty-five patients with a median age of 69 (range 22-82) were included in this study. Thirty-six had malignant tumors and nine had benign lesions (20%). The sensitivity of enhanced versus unenhanced PET/CT in the detection of pancreatic cancer was 96% versus 72% (P=0.076), the specificity 66.6% versus 33.3% (P=0.52), the positive predictive value 92.3% versus 80% (P=0.3), the negative predictive value 80% versus 25% (P=0.2), and the accuracy 90.3% versus 64% (P=0.085). CONCLUSIONS: Our preliminary data obtained in a limited number of patients shows that contrast-enhanced FDG PET/CT offers good sensitivity in the detection and assessment of pancreatic cancer, but at the price of a relatively low specificity. Enhanced PET/CT seems to be superior to unenhanced PET/CT. Further larger prospective studies are needed to establish its value for pre-surgical diagnosis and staging in pancreatic cancer.

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.

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.

Detection of micrometastases in sentinel lymph nodes from melanoma patients: direct comparison of multimarker molecular and immunopathological methods.

The technique of sentinel lymph node (SLN) dissection is a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) is emerging as a highly sensitive technique to detect micrometastases in SLNs, but its specificity has been questioned. A prospective SLN study in melanoma patients was undertaken to compare in detail immunopathological versus molecular detection methods. Sentinel lymphadenectomy was performed on 57 patients, with a total of 71 SLNs analysed. SLNs were cut in slices, which were alternatively subjected to parallel multimarker analysis by microscopy (haematoxylin and eosin and immunohistochemistry for HMB-45, S100, tyrosinase and Melan-A/MART-1) and RT-PCR (for tyrosinase and Melan-A/MART-1). Metastases were detected by both methods in 23% of the SLNs (28% of the patients). The combined use of Melan-A/MART-1 and tyrosinase amplification increased the sensitivity of PCR detection of microscopically proven micrometastases. Of the 55 immunopathologically negative SLNs, 25 were found to be positive on RT-PCR. Notably, eight of these SLNs contained naevi, all of which were positive for tyrosinase and/or Melan-A/MART-1, as detected at both mRNA and protein level. The remaining 41% of the SLNs were negative on both immunohistochemistry and RT-PCR. Analysis of a series of adjacent non-SLNs by RT-PCR confirmed the concept of orderly progression of metastasis. Clinical follow-up showed disease recurrence in 12% of the RT-PCR-positive immunopathology-negative SLNs, indicating that even an extensive immunohistochemical analysis may underestimate the presence of micrometastases. However, molecular analyses, albeit more sensitive, need to be further improved in order to attain acceptable specificity before they can be applied diagnostically.

Effect of peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, on dedifferentiated thyroid cancers.

BACKGROUND AND METHOD: As genetic alterations in the gene for the peroxisome proliferator-activated receptor gamma (PPARgamma) have been described and PPAR agonists have been shown to redifferentiate thyroid cancers in animal models, we performed a pilot study in five patients with thyroglobulin-positive and I scan-negative thyroid cancers using the PPARgamma agonist rosiglitazone. RESULTS: Although thyroglobulin levels increased in four of the five patients after 3 months of treatment with rosiglitazone, the I scan remained negative in four patients and became only faintly positive in one patient for two lung metastases that could be correlated with metabolically active lung metastases shown by F-fluorodeoxyglucose positron emission tomography (F-FDG PET) and by computed tomography (CT). F-FDG PET, performed in four patients, revealed metastases of significant size in two patients, including the patient mentioned above and in a second patient confirmed by surgery. CONCLUSIONS: Treatment with rosiglitazone increased the production of thyroglobulin in some patients with thyroid cancers, but only rarely restored scintigraphically significant iodine trapping. It remains to be shown whether longer treatment periods might result in a more efficient redifferentiating effect.

[¹¹C]acetate PET/CT visualizes skeletal muscle exercise participation, impaired function, and recovery after hip arthroplasty; first results.

PURPOSE: Based on skeletal muscle acetate physiology we aimed studying muscle function after hip arthroplasty with [(11)C]acetate PET. PROCEDURES: Two male patients were investigated 3 and 12 weeks after hip arthroplasty with muscle [(11)C]acetate PET/CT performed at rest and exercise. Median muscle SUV(mean) were calculated on three non-consecutive transverse PET slices. RESULTS: The four exercise PET/CT showed, compared with rest, consistent increase in [(11)C]acetate uptake in active muscles contralateral to surgery. On the arthroplasty side most muscles showed symmetric activity increase under exercise both at 3 and 12 weeks after surgery, but four muscles showed only minor activity increase at 3 weeks. At 3 months, functional recovery of the latter four muscles was observed. CONCLUSION: Consistent increase in [(11)C]acetate uptake in healthy muscles under exercise compared with rest was observed by PET/CT. Transiently impaired muscle function 3 weeks after surgery recovered at 3 months. These first observations merit further investigation.

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.