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Presents guidelines of the organizing committee Standards, Options and Recommendations for the use of positron emission tomography with 2-[[sup]18F]fluoro-2-deoxy-D-glucose (FDP-PET scanning) in oncology. Definition of Standards, Options and Recommendations and level of evidence; Advantages of positron emission tomography; Availability of scientific data and the development of Standards, Options, and Recommendations for the role of and indications for FDG-PET scanning in oncology.

BPH/2J mice are a genetic model of hypertension associated with an overactive sympathetic nervous system. Orexin is a neuropeptide which influences sympathetic activity and blood pressure. Orexin precursor mRNA expression is greater in hypothalamic tissue of BPH/2J compared with normotensive BPN/3J mice. To determine whether enhanced orexinergic signaling contributes to the hypertension, BPH/2J and BPN/3J mice were preimplanted with radiotelemetry probes to compare blood pressure 1 hour before and 5 hours after administration of almorexant, an orexin receptor antagonist. Mid frequency mean arterial pressure power and the depressor response to ganglion blockade were also used as indicators of sympathetic nervous system activity. Administration of almorexant at 100 (IP) and 300 mg/kg (oral) in BPH/2J mice during the dark-active period (2 hours after lights off) markedly reduced blood pressure (-16.1 ± 1.6 and -11.0 ± 1.1 mm Hg, respectively;P<0.001 compared with vehicle). However, when almorexant (100 mg/kg, IP) was administered during the light-inactive period (5 hours before lights off) no reduction from baseline was observed (P=0.64). The same dose of almorexant in BPN/3J mice had no effect on blood pressure during the dark (P=0.79) or light periods (P=0.24). Almorexant attenuated the depressor response to ganglion blockade (P=0.018) and reduced the mid frequency mean arterial pressure power in BPH/2J mice (P<0.001), but not BPN/3J mice (P=0.70). Immunohistochemical labeling revealed that BPH/2J mice have 29% more orexin neurons than BPN/3J mice which are preferentially located in the lateral hypothalamus. The results suggest that enhanced orexinergic signaling contributes to sympathetic overactivity and hypertension during the dark period in BPH/2J mice., (© 2016 American Heart Association, Inc.)

One of the main constraints associated with recording sympathetic nerve activity (SNA) in both humans and experimental animals is that microvolt values reflect characteristics of the recording conditions and limit comparisons between different experimental groups. The nasopharyngeal response has been validated for normalizing renal SNA (RSNA) in conscious rabbits, and in humans muscle SNA is normalized to the maximum burst in the resting period. We compared these two methods of normalization to determine whether either could detect elevated RSNA in hypertensive rabbits compared with normotensive controls. We also tested whether either method eliminated differences based only on different recording conditions by separating RSNA of control (sham) rabbits into two groups with low or high microvolts. Hypertension was induced by 5 wk of renal clipping (2K1C), 3 wk of high-fat diet (HFD), or 3 mo infusion of a low dose of angiotensin (ANG II). Normalization to the nasopharyngeal response revealed RSNA that was 88, 51, and 34% greater in 2K1C, HFD, and ANG II rabbits, respectively, than shams (P < 0.05), but normalization to the maximum burst showed no differences. The RSNA baroreflex followed a similar pattern whether RSNA was expressed in microvolts or normalized. Both methods abolished the difference between low and high microvolt RSNA. These results suggest that maximum burst amplitude is a useful technique for minimizing differences between recording conditions but is unable to detect real differences between groups. We conclude that the nasopharyngeal reflex is the superior method for normalizing sympathetic recordings in conscious rabbits., (Copyright © 2016 the American Physiological Society.)

New Findings: What is the central question of this study? Is the elevated tonic renal nerve activity induced by chronic angiotensin administration mediated by recruitment or increased firing frequency and does this occur via stress, chemoreflex or baroreflex pathways? What is the main finding and its importance? Long-term angiotensin treatment in rabbits elevates renal sympathetic nerve activity by recruitment of previously silent fibres. This was similar to the effect of chemoreflex stimulation, but not to stress or baroreceptor activation, suggesting that presympathetic pathways activated by angiotensin may be common to those activated by chemoreceptors. Modulation of sympathetic nerve activity involves control by the CNS of the amplitude of neural discharges, reflecting recruitment of neurons and their firing frequency. We tested whether elevated tonic renal sympathetic nerve activity (RSNA) induced by chronic angiotensin administration is mediated by recruitment or increased firing frequency and whether this is characteristic of the pattern observed with activation of stress, chemoreflex or baroreflex pathways. Conscious rabbits treated with angiotensin II for 12 weeks to increase blood pressure by 10-30% were subjected to stress (air jet), hypoxia (10% O2 + 3% CO2) and drug-induced changes in blood pressure to produce baroreflexes. Total RSNA and RSNA burst amplitude were scaled to 100 normalized units (n.u.) by the maximal response to smoke. After 12 weeks of treatment, blood pressure was 17% higher than baseline 68 ± 1 mmHg (P = 0.02). Compared with sham treatment, total RSNA and burst amplitude were +82% (P < 0.001) and 39% (P = 0.04) greater, but burst frequency was similar. Total RSNA increased during hypoxia (+38% from 4.9 ± 0.7 n.u.), owing to greater amplitude, but not frequency. Air-jet stress increased total RSNA (+44% from 4.3 ± 0.5 n.u.) and burst frequency (+21% from 5.4 ± 0.7 bursts s(-1) ), but not amplitude. Angiotensin enhanced total RSNA responses to both air jet (+33%) and hypoxia (+58%), but only increased the amplitude response to air jet. The RSNA baroreflexes reset to the higher blood pressure, but amplitude or frequency was not differentially altered. Chronic angiotensin treatment elevated RSNA by recruitment of neurons, which is similar to chemoreflex stimulation, but not to stress or baroreceptor activation, suggesting that presympathetic pathways activated by angiotensin may be common to those activated by chemoreceptors., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

Purpose: The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on (18)F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20 mm (T2-T4) were included in order to minimize bias of partial volume effect., Methods: In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV(max)) were compared to tumour characteristics as assessed on core biopsy., Results: There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV(max) was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p < 0.0001); negativity for oestrogen receptors (ER) was associated with higher SUV (ER+ SUV = 5.5; ER- SUV = 7.6; p = 0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p < 0.0001). Overexpression of c-erbB-2 had no effect on the SUV value., Conclusion: Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging.

Axillary node status is a major prognostic factor in early breast cancer. Staging with sentinel node biopsy (SNB) leads to a substantial reduction in surgical morbidity. Recent multiinstitutional studies revealed SNB false-negative rates ranging from 5.5% to 16.7%, higher than the target (<5%) set by the 2005 guidelines of the American Society of Clinical Oncology. These alarming data point to the necessity of optimization. Dual mapping with radiotracer and blue dye, combining 2 different injection sites, and routinely using lymphoscintigraphy may improve accuracy. Factors associated with decreased sensitivity, such as prior excisional biopsy or neoadjuvant chemotherapy, should be recognized. The use of SNB in situations with a high prevalence of node positivity (large tumor, multifocality) is controversial. The risk of missed disease after negative SNB ranges from 1% to 4% in patients with T1 tumor and up to 15% in patients with T3. With peritumoral injection, internal mammary drainage is seen in about 20% of cases. Patients combining internal mammary drainage with a positive axillary sentinel node have close to a 50% probability of internal mammary involvement. Lymphoscintigraphy might thus be helpful in selecting patients for whom internal mammary radiation has a high benefit-to-risk ratio.

Background and Aim: In internal radiotherapy, the variable distribution of target receptors within the tumoral tissue, and the variable ranges of electrons may be responsible for a heterogeneous dose distribution at the cellular level. The aim of the present study was to use Monte Carlo simulations to assess (131)I electron dose in a model of heterogeneous tumor containing multiple clusters of cancer cells, targeted by (131)I-labeled molecules., Methods: The model consisted of 150-μm-diameter spherical tumor cell clusters, in which (131)I was homogeneously distributed. Clusters were placed 24 μm apart, separated by septa of nonradioactive connective tissue. The electron dose distribution to tumor cells in a single cluster was first assessed. Then was assessed the dose increase to these targets after adding multiple layers of neighboring clusters (total number of clusters = 15,624)., Results: Dose distribution within a single isolated cluster follows a decreasing gradient, the dose for the outermost cell layer being about half that at the center. When radioactive neighbors were added, the dose to the central cluster increased. The most important contribution was given by the nearest neighbors, whereas the contribution from neighbors beyond a distance of 1 mm was only for 5% of the final dose. If the central cluster was unlabeled, the absorbed dose to the outermost cell layer of this cluster was reduced by 27%, and that at the center by 45%., Conclusions: The electron cross-dose of (131)I falls rapidly as a function of distance and becomes negligible after just 1 mm. Small clusters of tumor cells that are not radiolabeled may receive a very small dose. Therefore, in internal radiotherapy it is important to aim at targeting tumor cells as homogeneously as possible, rather than relying on the cross-dose to achieve a therapeutic effect.

Sentinel node status is the most powerful prognostic factor in patients with early-stage melanoma. This review discusses several issues of clinical interest and technical points for an optimized sentinel node biopsy (SNB) procedure. The role of fluorodeoxyglucose positron emission tomography/computed tomography is clearly established in patients with suspicion of locoregional or distant recurrence of melanoma before any surgical decision. However, its role at initial staging or follow-up of patients with localized disease or with positive SNB is less clear. Further research and efforts should focus on identifying which groups of patients are at specific high risk of early distant recurrence., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Accurate staging of Hodgkin's lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. (18)F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant (18)F-FDG PET/CT., Methods: Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and (18)F-FDG PET/CT. Results of BMB were not available at the time of (18)F-FDG PET/CT imaging., Results: Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on (18)F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on (18)F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy (18)F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient., Conclusion: (18)F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging.

Background: Parathyroidectomy (PTX), either subtotal or total with forearm autografting, is a well-established treatment for refractory renal hyperparathyroidism (RHPT). However, 20-30% of patients develop persistent or recurrent disease. Obtaining accurate localization before reoperation is difficult., Patients and Methods: The study group comprised 21 consecutive adult patients (18 undergoing haemodialysis and 3 with a renal graft) imaged using (99m)Tc-sestamibi/(123)I subtraction scintigraphy. Of the 21 patients, 12 had undergone one previous PTX and the other 9 between two and four parathyroid operations. All patients had symptoms and signs of severe RHPT. The mean serum PTH level was 1,142 pg/ml. (99m)Tc-Sestamibi and (123)I images were recorded simultaneously. Imaging views comprised a planar view of the neck and mediastinum, followed by a magnified pinhole view over the thyroid bed area. If parathyroid ectopy was detected, SPECT or SPECT-CT was performed. The forearm was imaged in case of autograft., Results: Parathyroid scintigraphy was negative in one patient and positive in the other 20 (sensitivity 95.2%). One patient had uptake corresponding to two unresected parathyroid glands. Recurrence at the site of the partially resected gland or autograft was seen in 11 patients. However, six of them had a second (99m)Tc-sestamibi focus corresponding to a supernumerary parathyroid gland. Seven other patients had a supernumerary parathyroid gland as the sole cause of relapse. Three of the supernumerary glands showed major ectopy (intrathyroidal, low mediastinal, undescended within the vagus nerve). One patient had parathyromatosis with multiple parathyroid nodules scattered over the left side of the neck. Reoperation was possible in 13 patients, with no false-positive findings., Conclusion: Many patients referred with the hypothesis of hyperplasia of a subtotally resected parathyroid gland or autograft were found to harbour a supernumerary parathyroid gland missed at the initial surgery.

Purpose: We tested the impact of different values of the relaxation parameter lambda (lambda) on contrast and noise in line-of-response row-action maximum likelihood algorithm (LOR-RAMLA) in 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) imaging., Methods: Phantom studies were performed on a Gemini XL PET/CT scanner. The NEMA/IEC (National Electrical Manufacturers Association/International Electro technical Commission) torso phantom was used and acquisition data were reconstructed with lambda values ranging from 0.025 to 0.1. Quality of the reconstructed images was evaluated by contrast recovery coefficients and background variability values according to the NEMA NU 2-2001 procedures., Results: Contrast recovery coefficients and background variability increased significantly when lambda increased. The best noise-versus-resolution trade-off was obtained with lambda in the 0.04-0.06 range. For LOR-RAMLA reconstruction, the manufacturer allows a possible lambda choice from 0.025 to 0.1. We would not advise too small (0.025) or too large (0.1) lambda values which result in too smooth or too noisy images., Conclusion: We determined optimal lambda values in LOR-RAMLA on a Gemini XL PET/CT scanner. Caution is needed when using lambda values out of that range.

Introduction: Positron emission tomography (PET) with 18F-FDG has become an important tool for the characterization of solitary pulmonary nodules (SPN)., Background: The results of the main meta-analyses show that the sensitivity and specificity of 18F-FDG PET for determining malignancy of SPN are close to 95% and 80% respectively. The limits of the technology are now well known. False negative results are mainly due to certain histological types with low metabolic activity (such as bronchiolo-alveolar carcinoma and typical carcinoid), or small size (nodules less than 8 mm). False positives are mainly represented by granulomatous and infectious processes., Viewpoints: A gain in accuracy occurred with the advent of hybrid PET/CT machines that combine the functional data from 18FDG-PET and the morphological data of computed tomography. Improved imaging protocols (eg. injection of iodinated contrast media) could further enhance the performance of PET-CT. Further improvements will rely on respiratory synchronization protocols and on the advent of new PET tracers., Conclusion: 18F-FDG PET-CT should be performed for any nodule over 8 mm in size when the pre-test probability of malignancy is not deemed negligible.

The authors discuss the various roles of 18F-FDG PET/CT in the management of breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and sodium fluoride (marker of bone matrix) are also mentioned. There is little justification for the use of FDG-PET/CT in patient with clinically T1 (< or = 2 cm) N0 tumours. Notably, it cannot be used as a substitute to SLNB "sentinel lymph node biopsy" for axillary staging due to limited sensitivity for the detection of small metastases. The case is different in higher risk patients, and especially so in patients with locally advanced disease. FDG-PET/CT in these patients might depict lymph node involvement in the level III of Berg or in supraclavicular or internal mammary basins. It might also uncover occult distant metastases, notably, early osteomedullary infiltration. Thus, for these tumors, initial PET/CT can enable better intramodality treatment planning or a change in treatment. PET/CT as a whole-body examination is also very efficient in case of suspicion of recurrence. On the other hand, many studies show that this functional imaging could be used to assess early response to neoadjuvant chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus become an unavoidable modality to answer various clinical situations.

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

The present paper addresses the advantages and limits of PET-CT in the work-up of cervical cancer. PET-CT is not to be overlooked in initial staging. It is useful to assess involvement of pelvic and lumbar lymph nodes. It can improve staging accuracy and help guide initial treatment such as optimisation of radiation therapy fields. Given its limited spatial resolution however, PET does not seem so adequate to document tumours less than 5 mm in diameter. It is not warranted for staging carcinoma in situ (FIGO stage 0) or preclinical carcinoma (FIGO stage 1A1 and 1A2). Furthermore MRI performances are best as far as local extension and tumour volume measurement are concerned. PET brings prognostic information. High initial uptake in tumour tissue or persistent increased uptake at completion of treatment indicates rather poor prognosis. PET is useful to evaluate therapy, but its exact role in this issue remains to be further refined. Finally, PET-CT can document early recurrence of disease.

Background: We used the Monte Carlo code "CELLDOSE" to assess the dose received by specific target cells from electron emissions in a complex environment. (131)I in a simulated thyroid was used as a model., Methods: Thyroid follicles were represented by 170 microm diameter spherical units made of a lumen of 150 microm diameter containing colloidal matter and a peripheral layer of 10 microm thick thyroid cells. Neighbouring follicles are 4 microm apart. (131)I was assumed to be homogeneously distributed in the lumen and absent in cells. We firstly assessed electron dose distribution in a single follicle. Then, we expanded the simulation by progressively adding neighbouring layers of follicles, so to reassess the electron dose to this single follicle implemented with the contribution of the added layers., Results: Electron dose gradient around a point source showed that the (131)I electron dose is close to zero after 2,100 microm. Therefore, we studied all contributions to the central follicle deriving from follicles within 12 orders of neighbourhood (15,624 follicles surrounding the central follicle). The dose to colloid of the single follicle was twice as high as the dose to thyroid cells. Even when all neighbours were taken into account, the dose in the central follicle remained heterogeneous. For a 1-Gy average dose to tissue, the dose to colloidal matter was 1.168 Gy, the dose to thyroid cells was 0.982 Gy, and the dose to the inter-follicular tissue was 0.895 Gy. Analysis of the different contributions to thyroid cell dose showed that 17.3% of the dose derived from the colloidal matter of their own follicle, while the remaining 82.7% was delivered by the surrounding follicles. On the basis of these data, it is shown that when different follicles contain different concentrations of (131)I, the impact in terms of cell dose heterogeneity can be important., Conclusion: By means of (131)I in the thyroid as a theoretical model, we showed how a Monte Carlo code can be used to map electron dose deposit and build up the dose to target cells in a complex multi-source environment. This approach can be of considerable interest for comparing different radiopharmaceuticals as therapy agents in oncology.

Introduction: In patients with a previous history of malignancy, the occurrence of a mediastinal mass with significant uptake of 18 Fluorodeoxyglucose on a PET-scan may lead to biopsy or resection., Case Report: We report the case of a posterior mediastinal mass, with significant uptake of 18 Fluorodeoxyglucose on PET- scan, in a patient with a previous history of testicular seminoma. The lesion was actually a benign schwannoma., Conclusions: In the case of a mediastinal mass with conventional imaging being in favour of a neurogenic tumour a PET scan cannot confirm benignity or malignancy.

Differentiated thyroid cancer, when adequately treated, has an overall good prognosis. However, 10-15% of patients develop distant metastases. The presence of metastases is an important prognostic factor that negatively affects survival. For (131)I-avid distant metastases, (131)I therapy is a very effective treatment modality that induces complete remission in about a third of patients. These figures may be even higher in case of early diagnosis, when tumor burden is still limited. Additional measures may include surgery and/or external beam radiation therapy. Cytotoxic chemotherapy is largely ineffective in patients with progressive, poorly differentiated cancer. These patients should be candidates for trials with new molecularly targeted therapeutic agents. In this paper, a review of diagnostic modalities, prognostic factors and therapeutic options for patients with distant metastases is proposed. In particular, the prognostic value of the early discovery of metastatic disease will be underlined.

This study aims to describe 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with AIDS-related Burkitt lymphoma, at various times of treatment, and to define its utility for a better patient management. We retrospectively studied 13 consecutive HIV-positive patients with Burkitt lymphoma who underwent one or more PET/CT. In 5 of 5 patients imaged before treatment, PET/CT confirmed all involved sites detected at conventional work-up and demonstrated additional sites in 4 of 5 patients. Lymph node involvement, which is known to be uncommon in endemic or sporadic Burkitt lymphoma, was present in 54% of patients. Additionally, in 3 patients, Burkitt lymphoma was predominantly located in parotid lymph nodes, which is also an unusual finding. A negative scan was encountered in 3 of 10 patients imaged during treatment and in 1 of 4 patients imaged after treatment completion and was always associated with lasting complete remission. Presence of residual area of uptake was related to both favorable and unfavorable outcome whether performed during treatment (5/7 and 2/7, respectively) or after (1/3 and 2/3, respectively). Areas of increased uptake could be observed in lung (4 cases) or esophagus (3 cases), and were clinically related to pneumonia or esophagitis. We recommend PET/CT for accurate initial staging of patients with AIDS-related Burkitt lymphoma. PET/CT is also useful to monitor treatment response, as regression of initial disease can be early observed. Furthermore, PET/CT appears to have prognostic value, as a negative scan was always associated with a favorable outcome.

We reviewed data from 160 consecutive patients (89 M/71 F; 53.5 [range, 9-88] years) who had under-gone lymphoscintigraphy and sentinel lymph node biopsy (SNB) in our hospital for histologically proven cutaneous malignant melanoma (CMM) (located on the upper limb: 33; lower limb: 57; trunk: 44; and head and neck: 26 patients), with a Breslow index > 1 mm and without clinical or radiologic evidence of metastatic spread. Colloidal (99m)Tc-rhenium sulfide (36-76 MBq) was injected intradermally in the four quadrants around the tumorectomy scar, followed by dynamic acquisition and static imaging. SN(s) were identified in 157 patients (overall identification rate, 98%). Fast (< 20 minutes), intermediate (20-30 minutes), or slow (> 30 minutes) lymphatic drainage was observed, respectively, in 122 (78%), 24 (15%), or 11 (7%) cases. Overall malignancy rate was 15%, respectively found in 19 (16%), 2 (8%), and 2 (18 %) patients with fast, intermediate, or slow drainage. No statistical difference between SN-positivity rates of patients with fast (19/122 = 16%) versus intermediate or slow drainage (4/35 = 11.4%) was observed (p = 0.69). Therefore, lymphoscintigraphic SN appearance time in CMM patients is unable both to predict SN metastasis and spare them from undergoing SN excision.

We examined the contribution of the renal nerves to mean arterial pressure (MAP) during 5-week chronic infusion of angiotensin II (Ang II; 50 ng/kg per minute SC) in conscious rabbits. Basal MAP was 68+/-1 mm Hg, and the maximum depressor response to ganglion blockade was -20+/-2 mm Hg. MAP increased by 25+/-2 mm Hg after 1 week and remained stable over the next 4 weeks. Depressor responses to pentolinium (6 mg/kg IV) were similar to control during the first week of hypertension but thereafter became increasingly greater in Ang II-treated rabbits but not vehicle-treated rabbits. After 5 weeks, the fall in MAP was 54% greater in Ang II- than in vehicle-treated rabbits (-34+/-2 versus -22+/-2 mm Hg), but renal sympathetic nerve activity was similar in both groups. Renal denervation produced a small fall in MAP in all of the vehicle-treated rabbits after 4 days (-6+/-2 mm Hg; P=0.01), but there was no consistent effect in hypertensive rabbits. The depressor response to ganglion blockade was enhanced in vehicle-treated but not Ang II-treated rabbits. The finding that renal sympathetic nerve activity is not altered by Ang II hypertension nor is the hypertension altered by renal denervation suggests that renal sympathetic nerves do not contribute to the hypertension. The greater depressor effect of acute ganglion blockade in hypertensive rabbits suggests that the sympathetic nervous system exerts increased vasoconstriction in the peripheral vasculature in Ang II-induced hypertension.

Background: Amiodarone has a high iodine content that can induce persistent iodine excess and may prevent radioiodine (RI) treatment., Patient: A 55-year-old obese man had taken amiodarone (200 mg/d) for 3 years and stopped 2 years earlier. He underwent total thyroidectomy for papillary cancer with extrathyroidal extension and a metastatic central lymph node, requiring RI treatment. But iodine overload, with no other documented iodinated drug intake, was found (urinary iodine excretion = 472 microg/24 h; normal < 150 microg/24 h), and persisted 3 months later. Plasma exchanges (PE) were prescribed., Interventions and Results: Eight PE over 4 weeks were needed to eliminate 39,295 nmol of iodine. Urinary iodine excretion and serum iodine concentrations, before PE and after eight sessions were, respectively: 230 and 84 nmol/mmol of creatinine, and 811 and 71 nmol/L, enabling RI treatment (4 GBq (131)I). Post-therapy whole-body scan revealed cervical uptake (0.48% of the total administered dose) corresponding to usual thyroid remnants. Ablation efficacy was confirmed 6 and 24 months later by cervical ultrasonography combined with an undetectable serum thyroglobulin level after recombinant human thyrotropin stimulation., Conclusions: When spontaneous iodine elimination is too slow to allow RI treatment of high-risk thyroid carcinoma within a reasonable time after thyroidectomy, PE are reliable and effective to overcome iodine overload.

Background: In patients with lymphoma who had a poor prognosis, pretransplantation 18-fluorodeoxyglucose (FDG)-positron-emission tomography (PET) was important for the evaluation of response and outcome. However, little is known about the correlation of FDG-PET with post-transplantation PET. The current study was designed to ascertain whether positive pretransplantation PET images are modified by the conditioning regimen., Methods: Sixty consecutive patients who had achieved remission and underwent consolidation by autologous stem cell transplantation (ASCT) had PET images obtained before ASCT (after 3 or 4 chemotherapy cycles) and 100 days after ASCT. The correlation was explored between the presence of abnormal 18-FDG uptake (PET positive) or its absence (PET negative) and patient outcomes., Results: Before ASCT, 31 patients achieved complete remission (CR), and 23 patients achieved uncertain CR. Before ASCT, 44 patients (75%) were had negative PET images; and, after ASCT, 48 patients (80%) had negative PET images. One year after ASCT, the estimated event-free survival (EFS) rate was 80% in patients who had negative pre-ASCT PET images compared with 43% in patients who had positive pre-ASCT PET images (P = .0002). The EFS rate was 81% in patients who had negative post-ASCT PET images compared with 25% in patients who had negative post-ASCT PET images (P < .0001). In multivariate analysis, only the results for pre- and post-ASCT PET images retained prognostic value, with relative risks of failure estimated at 4.9 and 11.9, respectively., Conclusions: A positive pre-ASCT PET image indicated a high risk of ASCT failure, which was increased by a positive post-ASCT PET image. For patients with lymphoma who have positive pre-ASCT PET images, more investigations using new treatment approaches will be required. For patients who have negative pre-ASCT PET images, obtaining post-ASCT PET images does not seem to be mandatory., ((c) 2007 American Cancer Society.)

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of (131)I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and (131)I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative (131)I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive (131)I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of (131)I. The bone metastases in the remaining eight patients were discovered on the post-surgery (131)I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to (131)I therapy, with (131)I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused (131)I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite (131)I therapy. Post-surgical (131)I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by (131)I therapy.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a technique of functional imaging whose interest in oncology does not cease growing. This article summarizes the results of the technique in senology. For the initial evaluation of locally advanced breast cancer (extended primitive lesion, axillary lymph nodes...), the FDG-PET makes it possible to evaluate lymph nodes (in particular internal mammary nodes) and to seek remote metastases. The sensitivity of the examination appears nevertheless low for the secondary lesions of small size and for bone metastases of osteoblastic form, for which the performances of the bisphosphonates scintigraphy are higher. For the search of a loco-regional or remote recurrence, the performances of FDG-PET are very interesting, including in the event of normality of the biological assessment. The impact of FDG-PET on the therapeutic strategy is undeniable and seems estimated at least 20%. FDG-PET is not recommended for the characterization of a breast lesion. In addition to the small tumoral size, the causes of false negative are mostly represented by the lobular histological form, by the tumours with low proliferation, the tumours of low grade and the well differentiated lesions. The causes of false positive are mainly in relation with inflammatory and/or infectious phenomena. For similar reasons, FDG-PET cannot replace the anatomy-pathological analysis of the axillary nodes. To evaluate the effectiveness of a neo-adjuvant chemotherapy, FDG-PET seems to be a powerful examination. Nevertheless, the data of the literature appear insufficient to recommend it in current practice. It is the same way for the prognostic interest.

We sought to investigate the apoptosis-inducing activities of quercetin, Siamois 1, and Siamois 2 against invasive estrogen-receptor negative MDA-MB 435 cells xenografted in athymic nude mice. This study clearly demonstrated that these compounds exhibited apoptosis-inducing activities in cell culture system. Quercetin (20 microg/mL), Siamois 1 (100 microg/mL), and Siamois 2 (200 microg/mL) can induce apoptotic cell death by 40 +/-5%, 44 +/- 14 %, and 31 +/- 13 %, respectively. Two-fold of IC50 of these compounds were clearly found to induce apoptosis in breast tumor tissue which can be determined by 99mTc-Annexin V scintigraphy and histological staining. This is the first report that the apoptosis-inducing effects of quercetin, Siamois 1 and Siamois 2 on the MDA-MB 435 cell in vitro were effectively extrapolated to the in vivo situation. These compounds might be considered as a simple dietary supplement and with further clinical investigation for their use as a nutrition-based intervention in breast cancer treatment.

Nuclear functional imaging is a reliable technique for the early evaluation of conventional cytotoxic and cytostatic agents. It also represents a major tool for the development and validation of anti-tumor targeted therapies.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program (SSP). The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information, developed in this program, is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres, the National League against Cancer, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The guidelines, "Standards, Options: Recommendations" (SOR) are used as primary information sources. The handbook SOR SAVOIR PATIENT Understanding positron emission tomography (PET) with [18F]-FDG in clinical oncology, integrally published in this issue of the Bulletin du Cancer, is an adapted version of the clinical practice guidelines (CPG) Standards, Options and Recommendations for positron emission tomography (PET) with [18F]-FDG in clinical oncology. The main objectives of this article are to allow persons affected by cancer and their close relatives to better understand this medical imaging technique and its implementation. This document also offers health professionals a synthetic evidence-based patient information source that should help them communicate that information during the physician-patient encounter. Positron emission tomography (PET) is a scintigraphy technique using a radiotracer, [18F]-fluorodeoxyglucose (abbreviated [18F]-FDG), administered intravenously into the patient's arm. This tracer, similar to glucose (sugar), binds to cancer cells and temporarily emits radiations that can be recorded by a special camera in the PET scanner. PET scanning can be used to obtain complementary information at different stages of the disease, whether for assessing diagnosis, treatment evolution or follow-up. By 2007, in the framework of the government plan against cancer, about seventy-five PET scanners are expected to be installed in France. Twenty-four are currently in use; a similar number is under installation. At the end of this process, all French regions should have at least one PET imaging equipment. The SOR SAVOIR PATIENT guide: Understanding positron emission tomography (PET) with [18F]-FDG in clinical oncology and the integral report of CPG SOR 2003: Standards, Options and Recommendations for positron emission tomography (PET) with [18F]-FDG in clinical oncology can be downloaded from the FNCLCC website: http:\\www.fnclcc.fr.

99mTc-sestamibi (MIBI) is a well-known tumour imaging agent. Its retention within tumour cell mitochondria is related to perfusion and to the magnitude of the electrical gradient, reflecting cell viability. Several internal cell factors modulate this uptake; for example, multidrug resistance membrane proteins (Pgp and MRP1) and anti-apoptotic BCl-2 protein of the outer mitochondrial membrane can limit retention of MIBI. At the early stage of cell apoptosis, the electrical driving forces of MIBI uptake are impaired, and influx and accumulation are reduced. It seems clear that MIBI can be used before treatment to detect drug resistance, assess anti-apoptotic status and predict treatment efficacy. Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance.

Rationale and Objectives: To investigate the relationship between CSF dynamics and risk of falls of unknown origin in the elderly., Population and Methods: Phase contrast MR studies allowed CSF aqueductal flow quantification on 23 community-dwelling older people initially explored for mild cognitive impairment. Mobility assessment included report of falls, talking walking test, stance test, one leg standing test, up and go test, and measurement of fast gait speed., Results: History of falls was associated with larger aqueduct, steeper diastolic slopes higher ratios RDV/SD of diastolic volume/CSF systole duration (p

Introduction: Diagnosis of carcinomas of unknown primary site has proved to be difficult for many reasons., Patient and Methods: In this study, case in which cerebral metastasis is confirmed by biopsy technique with no identified primary site at the onset of treatment is presented here in., Results: The multimolity medical images was used to detect pulmonary hearths compatibles with a malignant histology. Further analysis diagnosed a primitive neoplasm., Conclusion: This study illustrates the interest of this technology in medical imagery in the early detection of primitive cancers on which the forecast depends.

Natural products from plants such as flavonoids are potential drugs to overcome multidrug resistance (MDR) in cancer treatments. However, their modes of action are still unclear. In this study, the effects of quercetin on mitochondrial membrane potential (DeltaPsim) change as well as quercetin's ability to induce apoptosis and inhibit Pgp-mediated efflux of 99mTc-MIBI in K562/adr cells were investigated. Quercetin exhibits cytotoxicity against erythroleukemic cells: IC50 are 11.0 +/- 2.0 micromol/L and 5.0 +/- 0.4 micromol/L for K562 and K562/adr, respectively. Quercetin induces cell death via apoptosis in both K562 and K562/adr cells and does not inhibit Pgp-mediated efflux of 99mTc-MIBI. Quercetin (10 micromol/L, 3 h) and etoposide (100 micromol/L, 24 h) induce similar levels of apoptosis in K562 and K562/adr cells. Quercetin induces an increase followed by a decrease in |DeltaPsim| value depending on its concentration. A decrease in the |DeltaPsim| value is associated with an increase in the percentage of early apoptotic cells. It is clearly shown that quercetin results in a spontaneous DeltaPsim change during apoptotic induction. Therefore, quercetin is potentially an apoptotic-inducing agent, which reacts at the mitochondrial level.

Neuropilins (NRP) are receptors of angiogenic vascular endothelial growth factor (VEGF). Their overexpression was correlated with tumor angiogenesis and growth suggesting that their specific targeting could provide a new marker of tumor progression. Here, we observed in vitro that new (99m)Tc-labeled derivative of anti-VEGF heptapeptide, ATWLPPR, binds to NRP1 but not to NRP2. Our radiotracer is stable up to 24 h in human serum and in cysteine challenge. But, its too low affinity and too fast extraction indicate further improvement to give a successful imaging of tumor in vivo.