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Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome.

Purpose Prophylactic thyroidectomy has been encouraged for children with REarranged during Transfection (RET) germline mutations to prevent the onset, persistence, or recurrence of medullary thyroid carcinoma (MTC). The American Thyroid Association (ATA) recently published guidelines on the timing of prophylactic thyroidectomy. Our aim here was to seek information on the optimal timing of surgery for carriers of RET gene mutations with no clinical evidence of disease, bearing in mind the ATA recommendations. Methods From 1986 to 2012, total thyroidectomy was performed at our institute on 31 carriers of RET gene mutations, 28 of them found on family screening in the post-RET era, and the other 3 under 20 years of age and classified as "early cases" in the pre-RET era. The following parameters were studied: age at surgery, MTC risk, basal calcitonin (bCT) and pentagastrin-stimulated calcitonin (sCT), surgery outcomes, and persistence of disease. Results By family, the most prevalent mutation was codon 634 (30%) RET mutation. The youngest MTC patient was 5 years old. Overall, MTC was found in 68% of cases; 52% of the sample had a normal bCT and 25% had an sCT unresponsive to pentagastrin. The only factor predicting the risk of MTC at final histology was an ATA-RET risk level C. On receiver oparating curves analysis, a cutoff at age over 24 years predicted (P=0.06) a yield of MTC in the resected specimen. Interestingly, none of the patients with MTC had nodal involvement (0/21 patients with MTC). Yet, none of the patients had permanent nerve palsy, and only 1 patient had permanent hypocalcemia. bCT was normal postoperatively and during the follow-up in all but 3 patients. Conclusions It is noteworthy that the yield of cancer in removed thyroid was 100% for codon 634 (9/9 patients, 5 families) and for codons 891 and 768 (2/2 patients in each of the 2 families with those codon mutations), followed by 67% for codon 609 (4/6 patients, 1 family), and 60% for codon 618 (3/5 patients in 4 families) RET mutation. In cases of ATA-RET levels B and C, waiting for an increase in bCT and/or sCT may not guarantee that prophylactic surgery is performed before MTC develops (which would assure patients a life free of diseases and a less-invasive surgical procedure, without any need for central lymph-node dissection).

Aim. Despite its established utility in non-Hodgkin's lymphoma, not much is reported on FDG positron emission tomography (PET) with respect to radioimmunotherapy (RIT). In this paper we investigate its value in patients affected by follicular lymphoma (FL) before and after treatment with [Y-90]Ibritumomab Tiuxetan (Zevalin (R)). Methods. We evaluated 38 relapsed or refractory FL patients. All had a PET scan performed before and 3 months after radioimmunotherapy. Final assessment was done 9 months post-RIT, including clinical evaluation, other imaging techniques and/or biopsy, when necessary. Results. At the first PET scan 20 patients out of 38 had a limited disease (nodal involvement on one side of the diaphragm: 7 above and 13 below), 11 patients had nodal findings on both sides of the diaphragm and the remaining 7 patients had both nodal and extra-nodal findings. At three months post-KIT, 21 patients (55%) were in complete remission, 13 patients (34%) had a partial response (PR) and four patients (11%) had a progression disease (PD). The corresponding rates at final assessment were all consistent with the 3-month evaluation: 55% CR, 13% PR and 32% PD. FDG PET scan revealed maximal predictive values. When comparing the disease extent at relapse and the response to treatment, we could testify a higher rate of CR (75%) in patients with limited disease, while in patients with diffused nodal and/or extra-nodal findings, it was more frequent a PR or PD (66%). Conclusion. Our data are concordant with the expected results on MT, and FDG PET is confirmed to be useful in assessing treatment response. Potential correlation can also be picked out between the disease extent at relapse and the CR rate, with reasonable PET predictivity for the final outcome.

In this review, we focus on the oncological applications of positron emission tomography (PET) tracers other than [(18)F]fluoro-2-deoxy-D-glucose (FDG) and the novel quantitative approaches in PET imaging. Oncological non-FDG PET tracers can be broadly categorized into 3 groups: those labeled with (18)F, (11)C and other non-FDG tracers. Fluorine-18 and (11)C are labeled with different amino acids, substrates involved in fatty acid synthesis, protein synthesis, amino acid transport substrate and tracers linked to nucleic acid synthesis. These tracers are also labeled with specific ligands for receptor imaging (i.e. estrogens, dihydrotestosterone or somatostatin). The other non-FDG radiotracers can be labeled with (68)Ga, (60)Cu, (64)Cu, etc. and are aimed to detect cell hypoxia, bone metabolism and receptor. Many of these have shown promising results in the management of various cancers where FDG has limited role. These radiotracers have more specific mechanism of uptake and is likely be investigated in the near future. In the era of fusion imaging, novel approaches for accurate quantitative analysis include partial volume correction for measured values in small lesions, dual-time point and delayed PET imaging, and global metabolic activity for assessment of various stages of disease. Major changes are likely to occur in the future that may overcome deficiencies that are associated with the current quantitative (standardized uptake value) techniques.

Genitourinary (GU) tract cancers comprise a variety of tumors, which includes some of the most common malignancies in men and women. As a result of the importance of GU neoplasms and the success of positron emission tomography (PET) in imaging and staging cancer, PET with fluorodeoxyglucose (FDG) has been used to depict and stage ovarian, cervical and testicular cancers. The early success of FDG PET in imaging GU tumors is tempered by the fact that some neoplasms of GU origin do not accumulate sufficient FDG for successful imaging. As a result, alternative agents, such as [11C]choline and [11C]acetate, have been used to image prostate cancer and may have utility in bladder cancer, while other PET agents are currently under active evaluation for this and other GU neoplasms. In this paper, we review the current literature and our experience in role of PET in imaging cancers of the GU tract.

AIM: The aim of the present study was to assess the accuracy of an hybrid PET/CT scanner in the evaluation of newly diagnosed parotid masses, comparing the results with those reported in the literature with using PET scanners only. METHODS: The potential role of 18F-FDG PET/CT in distinguishing benign from malignant parotid masses in 14 consecutive patients was investigated. All patients were preoperatively evaluated by means of ultrasound (US), US-guided fine needle aspiration (FNA) cytology, computed tomography (CT) scan, magnetic resonance imaging (MRI) and 18F-FDG PET/CT. For To interpreting FDG PET findings, the right to left parotid (R/L) SUV max ratio was calculated in a group of 54 patients without evidence of parotideal disease (mean+/-SD = 1+/-0.2; range = 0.8-1.2); considering the R/L SUV max ratio, focal or diffuse uptakes 1.2 were considered as potentially pathological. RESULTS: Imaging data were compared with surgical and histopathological findings. At FDG PET/CT, 9 false positive cases were found (8 Warthin's tumours, 1 pleomorphic adenoma), 1 false negative (acinar cell carcinoma), 4 true negative (1 Warthin's tumour, 1 pleomorphic adenoma, 1 lymph epithelial cyst, 1 parotid inflammation) whereas there was no case of true positive. The global accuracy of FGD PET/CT was rather low = at 29%. CONCLUSIONS: In agreement with other preliminary reports in which the FDG PET without CT fusion imaging was used, in our experience 18F-FDG PET/CT did not prove to play a significant role in differential diagnosis (benign vs malignant) of parotid masses. Further studies collecting larger groups of patients are needed to further elucidate this observation.

Pathogenesis, natural course and therapeutic management of subclinical hypothyroidism (SH) in Down’s syndrome (DS) remain object of debate in literature. In the present study thyroid function, antithyroid antibody (ATA) prevalence and serum lipid concentrations were investigated in a group of 344 Down patients (DP) and data were compared with those obtained from a control group of 257 age and sex matched healthy subjects. Thyroid function and ATA prevalence were also studied in 120 parents of DP. SH prevalence was clearly higher in DP (32.5% of cases) than in controls (1.1%) and parents (0%). Similarly, ATA prevalence was higher in DP (18% of cases) than in controls (5.8%) and parents (6.6%). In spite of this, no correlation was found in DP between SH and ATA prevalences, since ATA were detected in 18.7% of SH-DP and in 15.8% of euthyroid DP. Thus, circulating ATA were not detected in the majority of SH-DP. No significant differences regarding T4, FT4, T3 and serum lipid levels among SH and euthyroid DP and controls were found. Moreover, TSH levels were only slightly increased, generally less than 10 μU/ml, in most cases of SH-DP. Follow-up was longer than 24 months (range 2–7 years, mean 3.1) in a group of 201 DP: two different patterns of SH course were observed, mainly depending on the presence or the absence of circulating ATA. In particular, 35.7% of ATA-positive SH-DP developed a clinically evident thyroid disease (overt hypothyroidism or hyperthyroidism), while no similar case was recorded among ATA-negative SH-DP. On the contrary, a significant number of these patients (33.9% of cases) showed a spontaneous normalization of TSH levels. The present data suggest that: a) DS per se seems to be a clinical risk condition in developing thyroid autoimmune diseases, b) SH represents a very common conditions in DP and in most cases it appears to be independent of the presence of circulating ATA, c) SH alone, that is in the absence of detectable ATA, does not seem to be predisposing condition to develop a clinically evident thyroid disease, as a spontaneous normalization of TSH levels is often observed. From the therapeutic point of view, it seems unlikely that L-thyroxine substitutive therapy could lead to some improvement in SH-DP in the absence of detectable ATA. A wait and see policy with frequent thyroid function screening could be considered adequate, thus avoiding chronic hormonal therapy at least in DP in whom TSH levels tend to spontaneously normalize. On the contrary, L-thyroxine should not be delayed in ATA-positive SH-DP due to the frequent evolution towards an overt thyroid disease.

In high-risk hypertensive subjects (HTs) with incidental unilateral renal artery stenosis (RAS), the effectiveness of percutaneous revascularization with stent (PR-STENT) on blood pressure (BP) and glomerular filtration rate (GFR) is not established.Eighteen HTs aged 65.7 ± 9.2 years with angiographically diagnosed unilateral RAS (≥ 60%) were randomized to receive PR-STENT (N=9) or to NO-STENT (N=9). BP (mercury sphygmomanometer) and GFR (99mTc-DTPA clearances during renal scintigraphy) were evaluated yearly for three years. Echo-Doppler of renal arteries was performed to verify the anatomic patency and flow velocities of the reperfused artery. Analysis of variance compared BP and GFR values changes from baseline to the follow-up; differences for continuous variables were evaluated between groups with the Tukey's post hoc test after adjustment for age, change of BP between baseline and at the follow-up, GFR and body mass index (BMI).Baseline systolic BP and GFR values were not different between groups. The significantly greater GFR increase observed in PR-STENT than in NO-STENT at univariate analysis at the end of follow-up (62.5 ± 19.2 vs. 42.24 ± 17.6, P0.02) disappeared after adjustment for confounding factors. However, systolic BP remained significantly lower in PR-STENT than in NO-STENT (140.1 ± 4.6 vs. 170.0 ± 8.3, P0.0001) also after adjustment for age, GFR and BMI.PR-STENT reduces systolic BP without improving GFR. Due to the strong association between high BP and renal damage, this study raises the question on whether PR-STENT should be performed in all HTs with unilateral and incidental RAS.

The identification of submandibular ectopic normal thyroid in the lateral neck with a coexisting normally located and functional thyroid gland is rare. Ectopic normal thyroid tissue in the midline location is most commonly related to aberrant migration along the thyroglossal duct (ie, lingual thyroid). A 54-year-old man with a 6-month history of visible asymptomatic swelling in the right submandibular region had ultrasonography and Tc-99m pertechnetate imaging.

Nodular goiter encompasses a spectrum of diseases from the incidental asyntomatic small solitary nodule to the large intrathoracic goiter causing pressure symptoms as well as functional complaints. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum thyroid-stimulating hormone (TSH), ultrasound (US) and other imaging procedures and cytology by fine needle aspiration (FNA) on the basis of the different diseases. A clinical classification considering solitary cyst, adenomatous functioning nodule, follicular lesion and multinodular goiter may be proposed to consider the alternative therapies other than surgery as TSH suppressive or thyrostatic treatment, 131I therapy, percutaneous ethanol injection therapy (PEIT) or the only clinical exam in benignant lesions. Surgery should be advocated for the treatment of thyroid nodules whenever a patient presents with either pressure symptoms, hyperthyroidism or follicular/indeterminate cytology. Surgical approach, intraoperatory strategy and the extension of surgical treatment are correlated to the different clinical categories. At surgery the frozen section analysis in case of hemithyroidectomy is of aid to rule out malignancy and to prevent the reoperation. The surgical treatment of choice in case of uninodular goiter is lobectomy, total thyroidectomy or near total thyroidectomy is the correct treatment of multinodular bilateral goiter. The choice of the treatment must be condivided with the patient.

Preoperative imaging has proved its use successful in the localization of solitary parathyroid adenomas in patients with suspected primary hyperparathyroidism. However, due to multiglandular disease at presentation patients with renal hyperparathyroidism need to be analyzed separately, making the usefulness of imaging techniques controversial. Recently, improved methods of functional imaging like parathyroid scan with 99mTc-sestamibi or positron emission tomography, especially when combined with computed tomography, can provide additional quantitative and qualitative information that has yet to be assessed. Nuclear medicine procedures could prove useful not only in preoperative diagnosis, but also in the selection of medical or surgical therapeutic alternatives in secondary hyperparathyroidism patients. There is evidence that 99mTc-sestamibi uptake in parathyroid hyperplasia or adenoma is related to biochemical markers of parathyroid function. We are only beginning to identify the factors involved in radiotracer uptake by parathyroid cells and how it can be modulated to obtain more accurate results. This review analyzes the current use of non-invasive imaging modalities in patients with secondary hyperparathyroidism, taking into account the latest trends in the field combining anatomic and functional modalities and the relevant factors linked to radiotracer uptake in abnormal hyperfunctioning parathyroid glands.

The human parathyroid glands, first described by Sandström in 1880, attracted interest because they were subject to inadvertent removal or ischemic injury during radical thyroid surgery. That this caused metabolic derangements was not known until many years later. Following on Kocher's studies, research continued to improve techniques sparing the parathyroids during thyroid surgery but without developing parathyroid surgery as such. For over a century, the lack of suitable surgical instruments, accurate preoperative localizing imaging techniques, and reliable laboratory tests hindered the evolution of parathyroid surgery, relegating it a marginal existence. Only after 1930, when it became clear that hyperparathyroidism is caused by an increased production of parathyroid hormone (PTH) by overactive parathyroid glands in the neck and/or the mediastinum, could parathyroid surgery, which shares a similar approach with thyroid surgery, be developed for treating hyperparathyroidism. The aim of parathyroid surgery is to cure hyperparathyroidism. Until advanced surgical and laboratory diagnostic technologies became available, concern about the risk of failure led surgeons to search all four glands by bilateral neck exploration, which proved unnecessary in 80% of cases. Recent years have seen parathyroid surgery evolve with the introduction of more efficacious preoperative localization imaging techniques and the use of rapid intraoperative parathormone assay, so that parathyroid surgery is now more selective and can be performed as a minimally invasive procedure in some cases.

The aim of the study was to evaluate the clinical role or [(99m)Tc]MIBI SPECT in selecting primary hyperparathyroid (PHPT) patients for minimally invasive radioguided surgery (MIRS).One hundred and forty-one consecutive PHPT patients were studied by a single-session [(99m)Tc]Percethnetate/[(99m)Tc]MIBI subtraction scintigraphy, followed by [(99m)Tc]MIBI SPECT in order to localize hyperfunctioning parathyroid adenoma (PA) and plan the surgical approach.A solitary PA was depicted at preoperative scintigraphy in 135 of 141 patients (95.7%), two or more PA in 5 patients, and was negative in 6 patients (4.3%). In 27 patients, the PA was located deep in the paraesophageal/paratracheal space. One hundred and twenty-four patients (in 18 of them the PA was located deeply in the neck) underwent successful MIRS using the low 37 MBq (1 mCi) [(99m)Tc]MIBI dose protocol. Intraoperative quick parathyroid hormone (QPTH) assay demonstrated a fall50% in respect to the baseline value in all patients, confirming successful parathyroidectomy. After a follow-up of 6 to 37 months (median 18 months), no case of persistent/recurrent PHPT was recorded. When comparing the parathyroid to background (P/B) ratio measured at planar and SPECT preoperative scintigraphy with that measured intraoperatively with the gamma probe, a significant linear correlation was found between the SPECT and intraoperative gamma probe measurements (r = 0.91; P0.01) while no correlation was found with planar scintigraphic data.Our data suggest that the P/B ratio calculated by means of [(99m)Tc]MIBI SPECT is more accurate in predicting the intraoperative measurements with the intraoperative gamma probe. Thus, a preoperative [(99m)Tc]MIBI SPECT acquisition should be recommended for a better selection of PHPT patients to offer MIRS.

BACKGROUND/MATERIAL AND METHODS: The aim of this study was to assess the reliability of radioiodine ((131)I) and a gamma probe for radio-guided surgery (RGS) to detect and radically dissect lymph node recurrence (LNR) in 15 patients with differentiated thyroid cancer (DTC). The major inclusion criterion was the presence of a radioiodine-positive LNR after previous total thyroidectomy and at least two ineffective (131)I treatments. The protocol was designed as follows: Day 0--all patients were hospitalized and received 3.7 GBq of (131) I while clinically hypothyroid. Day 3--pre-surgery whole-body scan with a therapeutic (131)I dose (TxWBS) was acquired. Day 5--neck surgery using a gamma probe (Navigator GPS, AutoSuture, Italy), recording the absolute counts and the lesion/background (L/B) counts ratio was performed. Day 7--post-surgery TxWBS was performed using the remaining radioactivity.This protocol permitted us to identify neoplastic foci with high sensitivity and specificity, enabling us to remove lymph node metastases resistant to radioiodine therapy in a single session. The protocol also allowed detection of some additional tumoural foci in sclerotic areas or behind vascular structures that were not seen at the pre-surgery TxWBS evaluation.

SummaryThe aim of this study was to investigate the efficacy of minimally invasive radio-guided parathyroidectomy (MIRP) in primary hyperparathyroid (PHPT) patients. Patients, methods: 452 consecutive PHPT patients were evaluated. Inclusion criteria for MIRP were (a) evidence at scintigraphy of a solitary parathyroid adenoma (PA); (b) a clear sestamibi uptake in the PA; (c) the absence of concomitant thyroid nodules; (d) no history of familial HPT or MEN; (e) no history of previous neck irradiation. Intra-operative protocol consisted of the injection of a low 37 MBq sestamibi dose in the operating suite 10 min before surgery. A hand held 11-mm collimated gamma probe was used. Quick PTH (QPTH) was routinely measured. Results: 344 out of the 452 patients met the inclusion criteria, and MIRP was successfully performed in 321 of them (93.3%). No major intra-operative complication was recorded. MIRP required a mean operative time of 32 min, and a mean hospital stay of 1.2 d. The parathyroid to background ratio (P/B) calculated by the probe was well correlated with the P/B calculated by sestamibi SPECT (r = 0.91; p

In the last 10 to 15 years surgery of primary hyperparathyroidism (PHPT) moved from the wide bilateral neck exploration to various types of limited neck exploration ranging from unilateral neck surgery to minimally invasive approaches as the minimally invasive radioguided parathyroidectomy. In contrast with the bilateral neck exploration, an accurate preoperative localizing imaging, which is mainly based on (99m)TC-sestamibi scintigraphy, is mandatory when planning a concise parathyroidectomy. Following imaging criteria, only a fraction of PHPT patients accounting for approximately 60% to 70% of all PHPT patients can be eligible for a minimally invasive parathyroidectomy. Only PHPT patients with a high probability to be affected by a solitary parathyroid adenoma showing a high (99m)TC-sestamibi uptake and with a normal thyroid gland should be offer a minimally invasive radioguided parathyroidectomy. The (99m)TC-sestamibi SPECT technique and the double-tracer 123-iodine or (99m)TC-pertecnetate/(99m)TC-sestamibi scintigraphic technique are the most sensitive and accurate preoperative imaging modalities and their utilization is recommended when considering a minimally invasive radioguided parathyroidectomy. Two main intraoperative procedures for the minimally invasive radioguided surgery have been described: the single-day protocol and the different-day protocol. In the single-day protocol a 740 MBq dose of (99m)TC-sestamibi is injected to the patient, scintigraphic imaging is obtained by dual-phase technique and then the patient is operated on within approximately 3 hours from radio-tracer injection. In the different-day protocol, a double-tracer parathyroid scintigraphy is obtained some days before surgery with the aim of better planning the type and extension of intervention. The day of intervention, for the purpose of radioguided surgery only, a low 37 MBq dose of (99m)TC-sestamibi is injected to the patient in the operating theatre a few minutes before the start of intervention. The main advantages of minimally invasive radioguided parathyroidectomy over the traditional wide bilateral neck exploration can be resumed as follows: a shortening in the operating and recovery time, possibility of local anesthesia, possibility of ambulatory surgery or same-day discharge, less postsurgical hypocalcemia, less postsurgical pain, favourable cosmetic results, benefits from a cost-analysis point of view.

The case of a female patient affected by a sporadic medullary thyroid carcinoma (pT1N1aM0 at the onset) is reported. The patient had been initially treated by total thyroidectomy and lymphadenectomy of the central and lateral portions of the neck. During the following 30 years of follow-up, the patient experienced 3 consecutive loco-regional tumoral relapses. At the moment of each relapse, an increase of serum calcitonin levels has anticipated the subsequent detection of tumor deposits at clinical and radiological examination (ultrasound, CT scan). It is well known that, after multiple operations, the structures of the neck can present anatomical distortion and fibrosis that can interfere with ultrasound and CT scan interpretation. In the present patient, a scintigraphic examination with 111In-octreotide, that is a specific radio-tracer for somatostatin receptors, allowed to correctly visualize a tumoral relapse in the left thyroid bed, located in deep para-tracheal planes: in that site the CT scan only showed an unspecific solid mass. Furthermore, the utilization of a digital image fusion technique for CT scan and 111In-octreotide SPECT, furnished useful information for the purpose of planning an accurate re-intervention, both morphologic information (mass size, precise site of the mass and their relationship with the surrounding anatomical structures) and functional information (biological characterization of the mass that was classified as a neuroendocrine tumoral deposit with high density of somatostatin receptors.

Disorders of the upper digestive tract have a high impact on modern society, in terms of both direct and indirect health care costs and of social burden. The most common presenting symptom is either dysphagia or dyspepsia. Discriminating specific diagnoses within this wide group of diseases requires sound clinical judgment and application of procedures to distinguish organic from nonorganic disease and to further characterize the functional or motility disturbance of nonorganic diseases. Non-radionuclide-based diagnostic techniques include both noninvasive tests (upper gastrointestinal barium series, ultrasonography, and breath test for gastric emptying) and invasive procedures (fiberoptic endoscopy, esophagogastroduodenoscopy, pharyngeal manometry, stationary esophageal manometry, 24-h pH monitoring, esophageal biliary reflux monitoring, multichannel intraluminal impedance, and electrogastrography). Some of these techniques are not well tolerated by patients or not widely available. Radionuclide transit/emptying scintigraphy provides a means of characterizing exquisite functional abnormalities with a set of low-cost procedures that are easy to perform and widely available, entail a low radiation burden, closely reflect the physiology of the tract under evaluation, are well tolerated and require minimum cooperation by patients, and provide quantitative data for better intersubject comparison and for monitoring response to therapy. Despite the relatively low degree of standardization both in the scintigraphic technique per se and in image processing, these methods have shown excellent diagnostic performance in several function or motility disorders of the upper digestive tract. Dynamic scintigraphy with a radioactive liquid or semisolid bolus provides important information on both the oropharyngeal and the esophageal phases of swallowing, thus representing a useful complement or even a valid alternative to conventional invasive tests (such as stationary esophageal manometry) for evaluating abnormalities of oropharyngoesophageal transit. Clinical applications of esophageal transit scintigraphy include disorders such as nutcracker esophagus, esophageal spasm, noncardiac chest pain of presumed esophageal origin, achalasia, esophageal involvement of scleroderma, and gastroesophageal reflux and monitoring of response to therapy (either medical or surgical treatment of disease-for example, organic disease such as esophageal cancer). Scintigraphy with a radiolabeled test meal represents the gold standard for evaluating gastric emptying, whereas more recent radionuclide methods include dynamic antral scintigraphy and gastric SPECT for assessing gastric accommodation. Clinical applications of gastric-emptying scintigraphy include, among others, evaluation of patients with dyspepsia and evaluation of gastric function in various systemic diseases affecting gastric emptying. The present review includes the proposal of clinical algorithms for evaluating patients with the main disorders of the upper digestive tract. These algorithms, originally derived from available literature, have been developed on the basis of a vast clinical experience in conjunction with the specialists more deeply involved in the care of patients with such disorders (medical and surgical gastroenterologists and nuclear medicine physicians). The role of radionuclide gastroesophageal motor studies is clearly identified in the various steps of patients' management, from the initial diagnostic approach to functional characterization to postoperative follow-up or monitoring of medical therapy.

Positron emission tomography (PET) is considered one of the most effective nuclear medicine imaging modality in oncology. In many types of malignant tumours PET has proven to be high sensitive in detecting both primary neoplasm and metastatic disease both before therapy for staging purposes and after surgery, radiotherapy and chemotherapy during follow-up. In particular, PET showed high accuracy in differentiating post-treatment scar from viable tumoural tissue and high sensitivity in visualising very small metastatic foci as those in normal-sized (less than 1 cm in diameter) lymph nodes. A large variety of positron emitter tracers have been produced for PET imaging: the most widely used tracer in clinical oncology is 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Deoxy-glucose (DG) is a glucose analog that enters the cell using specific transmenbrane carrier proteins (especially GLUT-1). Once within the cytoplasm, DG is phosphorylated to FG-6-phosphate but does not appear to be further metabolised. In most malignant tumours there is an increase of the glycolityc metabolism which accounts for an increase of the FDG uptake. However, the metabolic cellular activity can be only slightly increased or even normal in well differentiated and slow growing tumours as some endocrine neoplasms. In the present review, the clinical usefulness and limits of PET imaging are discussed in the management of patients with endocrine tumors.

Carcinoma of the parathyroid is a rare endocrine tumour which can be difficult to diagnose even for expert anatomopathologists.A retrospective study was carried out on all the cases of parathyroid pathology observed between January 1980 and October 2000: parathyroid carcinoma was diagnosed in 17 (3.59%) out of 478 patients treated for hyperparathyroidism. We describe their clinical presentation, treatment and results obtained. The patients included 9 women and 8 men, with a male/female ratio of 1.14 and a mean age at diagnosis of 56.9 years (range 30-83). All the patients, except one, the only non-secreting case, presented hypercalcemia, and 10 patients presented serum calcium levels above 3 mmol/L. The symptoms at onset included: nephrolithiasis in 10 cases, osteoporosis in 4 (3 of which presented uremic syndromes), gastrointestinal symptoms (gastritis) in 1 case, a palpable cervical mass in 1 patient and recurrent nerve palsy in one case suffering from familial IPT. A variety of imaging techniques were used for the preoperative localisation: high-resolution ultrasonography of the neck was carried out in all 17 patients and was positive in 15 cases; scintigraphy (99mTcO4/201Tl or 99mO4/MIBI) was carried out in 16 patients and was positive in 14; CAT was positive in 6 out of 17 patients. Three patients underwent the first operation in another hospital and were referred to our department for resistance or recidive. Initial surgery was restricted to simple parathyroidectomy in 4 cases; parathyroidectomy was extended to the entire gland in 3 patients with uremic syndrome and to the ipsilateral thyroid lobe in 7 cases. Three patients underwent parathyroidectomy extended en bloc to the adjacent structures, and recurrent lymph node dissection was also performed in 2 of these patients. Lymph node involvement was never demonstrated during the first operation. The dimensions of the tumour varied from 1 to 6.7 cm; we found signs of invasion of the neighbouring structures in 3 patients.Parathyroid carcinoma was correctly diagnosed during the first operation in 14 cases (this diagnosis was suspected in 10 cases following intraoperative frozen session), whereas the first diagnosis was of benign disease in 3 patients. Blood levels of calcium, phosphorus and PTH returned to normal after the first operation in 13 patients. These values diminished, but did not return to normal in 2 cases. Two patients relapsed, respectively 5 and 175 months after the first operation. A total of 10 reoperations were performed in 4 patients with persistent/recurrent symptoms (from a minimum of 1 to a maximum of 4). Recidive presented characteristics of local invasiveness in one case and the persistence was supported by micro-insemination of the pre-thyroid compartment and muscles in another two cases. At reoperation, lymph node metastasis was associated with local recidive only in one case. Two patients underwent radiotherapy after surgery and one received chemotherapy. At the last check-up (October 2000), 14 patients were alive and disease-free (82.25%). Two presented slight persistent hypercalcemia (with values ranging between 2.65 and 2.80 mmol/L), but without any macroscopic localisation of disease (11.76%). Only 1 patient died (5.88%) (one year after the first operation and 7 months after the last one). Death was caused by uncontrollable hypercalcemia supported by widespread metastasis to the bones and lungs. The 5 and 10-year survival rates were calculated as 94.12%.In conclusion, high blood levels of calcium and PTH, a palpable mass at the neck, with recurrent nerve paralysis, aspects of local invasiveness should alert the surgeon and guide him towards surgery that includes resection of the parathyroid en bloc with the adjacent structures, although there is no proof that a more extensive surgery is correlated with a more favourable prognosis. Being the majority of recidive functional, monitoring serum calcium and PTH levels offers a useful market which precedes their macroscopic demonstration.

The aim of this study was to define the clinical impact of MIBI scan combined with neck ultrasonography on the detection of metastates in differentiated thyroid carcinoma (DTC) patients with elevated serum Tg levels but negative 131I scan (non-functioning DTC).Eighty-two patients with non-functioning DTC, 19 patients with 131I-positive metastases (functioning DTC), and 24 DTC patients who were disease free after therapy (no cancer patients) were enrolled. 131I scan was performed after administration of low diagnostic and high therapeutic tracer doses. Early and delayed images were obtained after MIBI injection. Neck-chest CT scan and/or MRI were also performed in patients with non-functioning DTC.In the group of non-functioning DTC patients, metastatic foci were detected in 71/82 cases: in the cervical lymph nodes in 51 cases (sensitivity 94.1% with MIBI, 90.2% with US, 35.3% with CT/MRI), mediastinal lymph nodes in 31 cases (sensitivity 100% with MIBI, 58% with CT/MRI), lungs in 8 cases (sensitivity 100% with both MIBI and CT/MRI), and bone in 2 cases (sensitivity 50% with MIBI, 100% with MDP bone scan). Among the 19 patients with functioning DTC a close relationship between MIBI and 131I findings was observed. As regards the 24 tumor-free patients, MIBI was correctly negative in all cases, while US visualized enlarged cervical lymph nodes that were suspected to be neoplastic but proved to be inflammatory lesions at cytology in three patients.On the basis of these data, MIBI scan combined with neck US could be proposed as a first-line diagnostic imaging modality in the follow-up of DTC patients with elevated serum Tg levels and negative 131I scan.

BACKGROUND: Despite being a relatively rare disease, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next two decades due to the long time interval elapsing between exposure to causative factors, mainly asbestos, and disease onset. Early disease stages have been reported to benefit from radical surgery. In more advanced disease stages, a multimodality treatment, including various combinations of chemotherapy, external radiotherapy and surgery, may provide some favourable results though the prognosis remains poor. In this regard, an accurate pre-treatment staging plays an important role in offering patients a more appropriate therapeutic planning. In some preliminary studies, (18)F-FDG PET has proven to be able to provide useful information for staging purpose, especially for the detection of metastatic spread to lymph nodes and distant sites. MATERIAL AND METHODS: In the present study, we investigated 15 consecutive patients with histologically proven MPM by means of conventional 2-mm thickness whole-body CT scan with and without contrast medium in comparison with wholebody (18)F-FDG PET/CT fusion imaging. RESULTS: (18)F-FDG PET/CT did not provide additional information about the primary tumour (T) compared to CT scan, but identified a higher number of metastatic mediastinal lymph nodes (N) in 6 patients (40% of cases) and unknown metastatic disease to distant sites (M) in 3 patients (20% of cases). On the basis of PET/CT findings, treatment planning was changed in 5 patients (33.3% of cases). CONCLUSIONS: Our data show that (18)F-FDG PET/CT fusion imaging can play a relevant role in the staging and treatment planning of MPM patients.

To evaluate the value of 18F-fluorodeoxy-glucose (FDG) positron emission tomography with computed tomography (PET/CT) in myeloma in patients presenting with a solitary plasmacytoma of bone (SPB).Fourteen consecutive patients studied since 2006, all having a diagnosis of SPB before PET/CT imaging took part in this study. In 3 patients PET/CT was performed for staging while in the remaining 11 it was used to monitor therapy. PET/CT was performed using a dedicated tomograph 60-90 minutes after intravenous injection of 53 MBq/kg of 18F-FDG and the results were compared to other diagnostic procedures [radiographs and magnetic resonance imaging (MRI)], biopsy, and other available follow-up data.In 8/14 patients, PET/CT scans showed previously unsuspected sites of increased FDG accumulation. In 6/8 patients, FDG uptake was considered pathologic, depicting myeloma involvement in bone, while in the remaining cases, findings were considered incidental and not related to myeloma. PET findings attributed to myeloma were confirmed (i.e. true positives) in 6/6 cases (100%) and in all patients with findings reported as non-pathologic, myeloma was excluded (100% true negatives).Our preliminary data in a small number of cases suggests that there are a group of patients with SPB (local disease) in whom FDG PET/CT may detect other unsuspected sites of bone involvement, upstaging the extent of the disease. In these cases, SPB may be a local manifestation of multiple myeloma where other sites of involvement have eluded detection by other less sensitive imaging modalities (i.e. skeletal surveys) or anatomically restricted imaging (i.e., less than total body MR or CT). Finding other sites of involvement have significant implications for appropriate treatment of myeloma.

The established treatment for differentiated thyroid carcinoma (DTC) is founded on total thyroidectomy and subsequent administration of radioiodine (131I) to ablate the thyroid remnant and to treat the metastatic disease. In the case of metastatic or recurrent disease, further cycles of 131I therapy are often necessary. The condition for maximizing the effectiveness of the treatment is to have an adequate stimulation from TSH, which must be25-30 mIU/L. This elevation is achieved either discontinuing the hormone suppression therapy for an appropriate period, or administering recombinant human TSH (rhTSH). The latter has shown good clinical efficacy in patients with residual thyroid gland and is nowadays commonly employed since it is easy to use and allows to avoid the side effects of hypothyroidism. It thus represents a good alternative to thyroid hormone withdrawal for the remnant ablation, while is still open the question if its efficacy on the management of metastatic disease is superimposable to thyroid hormone withdrawal. To this purpose, a Panel of expert reviewed the literature, assessing the advantages and disadvantages for the patient, as well as the impact in terms of cost and benefit to the National Health Service. The work of the Panel concluded with a proposal for the use of rhTSH in selected patients with metastatic DTC, in which is considered the efficacy and safety of the product and is examined its use in terms of costs; this proposal was accepted by the Italian Drug Agency resulting in an update of the indications for rhTSH.

In the last decade important progresses have been obtained in the diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors, mainly derived from the somatostatin receptors characterization and the introduction of long acting somatostatin analogues. Receptorial scintigraphy with radio-labeled analogues (Octreoscan) is the first choice investigation for staging and follow-up of endocrine GEP tumors, thanks to the high sensitivity in revealing the primary tumor and metastases, and for its capability to reveal lesions that are not identified by other imaging methods. Moreover, somatostatin analogues uptake by tumors allow us to use radiopharmaceutical compounds for advanced disease treatment. Between the radio-labeled drugs until now studied, interesting results have been obtained by DOTA-lanreotide (MAURITIUS), DOTA0 Tyr3-octreotide (DOTATOC) and DOTA0 Tyr3-octreotate, bound to beta-emitting radio-isotope suitable for therapeutic use. In the field of the pharmacological therapy of GEP tumors, the clinical trials show that somatostatin analogues reduce the symptoms related to functionally active tumors and stabilize or slow tumor growth improving the patient quality of life. Although somatostatin analogues alone could not be able to cure GEP tumors, their early utilization in association with surgical debulking of primary tumor and metastases, embolization or chemoembolization, and interferon, chemotherapy and radio-metabolic therapy (mainly directed to the destruction of micrometastases), increases the possibility of a radical therapeutic intervention. The continuous evolution of pharmacological research provides always new analogues (octreotide LAR, lanreotide, vapreotide, BIM-23244, BN 81644, PTR-3173, BIM-23A387, SOM-230, etc.) with different pharmacokinetic and receptorial properties and acting with more effectiveness in the different individual clinical situations. In this context there have been recently introduced also the "chimeric" analogues. On the other hand, the widespread utilization of molecular biology and immunohistochemical methods can allow, in perspective, to better define the receptorial pattern of individual endocrine tumors, after their surgical removal. The necessity to integrate endocrinological, nuclear medicine, surgical, oncologic and laboratory competencies behaves a multidisciplinary approach based on the utilization of diagnostic-therapeutic protocols supplying comparable results. It does not appear unjustified to expect, in the future, a scenery of more "individual" and more effective therapies for patients affected by GEP tumours.

Thyroid dysfunctions may be accompanied by numerous neurological and psychiatric disorders. The most known is cognitive impairment and depression in hypothyroid patients, as well as an increased risk of cerebrovascular accidents. A separate, although a rare entity, is Hashimoto's encephalopathy. In hyperthyroidism there is an increased incidence of psychiatric disorders, including apathetic hyperthyroidism and hyperthyroid dementia. Functional imaging of cerebral blood flow and metabolism helped establish both global and/or regional decrease of both cerebral blood flow and metabolism in hypothyroidism, particularly in regions mediating attention, motor speed and visuospatial processing. Hypothyroid dementia may be mediated by neurocircuitry different from that in major depression. Less is known on flow/metabolism changes in hyperthyroidism. Global blood flow may be slightly increased, with regional deficits of blood flow, particular in hyperthyroid dementia. As presented above radionuclide functional imaging showed some metabolic patterns in thyroid dysfunctions, but still many issues remain unresolved. In particular little is known about the underlying pathology of cognitive impairment and depression in hypothyroidism, which may differ from ones in euthyroid patients. Also little is known about the reversibility of changes in cerebral blood flow following thyroid replacement therapy. In hyperthyroid patients functional imaging might contribute to elucidate the background of apathetic hyperthyroidism and potential different background of psychiatric complications.

In the diagnostic assessment of medullary thyroid carcinoma (MTC), nuclear medicine imaging provides its contribution mainly in the postoperative work-up to detect residual or recurrent tumor. With respect to scintigraphy with gamma-emitter radiopharmaceuticals, positron emission tomography (PET) offers interesting perspectives owing to its higher image quality, spatial resolution and speed. Moreover, the recent developments of hybrid machines allow to obtain images that simultaneously hold both anatomic (computed tomography) and functional (PET) information with great impact on diagnostic efficacy. (18)F-fluoro-deoxyglucose ((18)F-FDG) is the most frequently used PET tracer in oncology. Preliminary reports of FDG-PET in MTC patients show encouraging results with a higher sensitivity in detecting local recurrent and metastatic disease when compared with single photon emission tracers. However, (18)F-FDG uptake depends on lesion size and to some extent on the grade of differentiation and biologic aggressiveness of the tumor; so FDG-PET seems useful mainly in patients with very high calcitonin levels and high progression rate. Like other neuroendocrine tumors, MTC is characterized by the presence of amine uptake mechanism and/or peptide receptors at the cell membrane allowing the clinical use of specific radiopharmaceuticals that reflect the different metabolic pathways of MTC, and in particular the synthesis, storage and release of hormones ((18)F-dihydroxyphenilalanine, (18)F-DOPA and (18)F-fluorodopamine, (18)F-FDA) and the expression of receptors ((68)Ga-labeled somatostatin analogs). These tracers are currently under investigation and will further improve the diagnostic approach of MTC.

Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. Several large-scale studies have reported a relatively high false-negative rate (5.6-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the prognosis of melanoma patients. Indeed, most studies have failed to show that there is worse melanoma-specific survival for false-negative compared to true-positive SLNB patients.

Glomerular filtration rate (GFR) is commonly calculated using the modification of diet in renal disease (MDRD) and Cockroft-Gault (CG) formulas and recently by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm and not directly measured, so that the real impact of antihypertensive therapy on GFR could not be well defined. In this study, the effect of Aliskiren on the GFR measured by radionuclide clearance of 99mTc-diethylene triamine penta-acetic acid (DTPA) was investigated.In 106 hypertensive subjects (53% men) aged 61.9±12.7 years with uncontrolled blood pressure (BP) receiving at least 2 antihypertensive medications, Aliskiren was added once-daily at a dose of 150-300 mg for 12 months. Clinic BP measurements were taken at every follow-up visit (1st, 6th and 12th month), while 24-hours ambulatory BP and GFR (in mL/min/1.73 m2) were evaluated at baseline and at the end of the follow-up. Analysis of variance for repeated measures of BP, GFR and microalbuminuria was provided.With the use of Aliskiren a significant reduction of BP and microalbuminuria was found (P0.0001). Only in male population, a significant reduction in GFR calculated with CKD-EPI (82.4±15 vs. 78.6±18.2, P0.01) and CG (81.6±29.5 vs. 74.2±28.4, P0.0001) formulas was observed. This impairment of GFR was not found either with MDRD formula (70.5±19.6 vs. 68.3±23.4) or by radionuclide clearance (62.4±18.6 vs. 61.4±20.5).This study seems to demonstrate that the efficacy on BP control of Aliskiren is not accompanied by an impairment of GFR. In order to evaluate the effect of Aliskiren on GFR scintigraphy technique or MDRD formula resulted to be the most accurate methods.

111In-Octreotide scintigraphy has been recently proposed as a sensitive technique for the detection of neuroendocrine tumours, based on the high radiotracer affinity towards the somatostatin receptors expressed by the APUD-system cells. In the present study, a group of 18 patients with carcinoid tumours and gastrointestinal (GI) apudomas was investigated to assess the accuracy of Octreotide scintigraphy in localizing primitive, recurrent or metastatic lesions. Both planar and SPECT studies were obtained 4 hours after the i.v. injection of 111In-Octreotide (111 MBq); planar images were also carried out 24 hours later. In accordance with other authors, the sensitivity of the method was found to be very high (94%) in our group of patients; only in one case of nesidioblastosis was the scintigraphy negative. No differences in sensitivity were observed between the planar and SPECT studies, but the latter provided a better topographic localization of the neoplastic foci. It should be pointed out that in 7 cases (3 primitive, 1 recurrent and 3 metastatic lesions) scintigraphy correctly localized the tumour, when the other morphological techniques, such as echography, computed tomography or magnetic resonance, failed. On the basis of our data, we believe that Octreotide scintigraphy should be the first study performed in the evaluation of patients affected by APUD tumours.

Recently, in Italy, the reimbursement for the use of rhTSH in preparing patients for radiometabolic treatment of iodine-avid metastases from differentiated thyroid cancer has been made possible. Intramuscular administration of rhTSH increases the radioiodine uptake and thyroglobulin production by thyroid cells. In addition to the previous indications on the use of rhTSH (mainly: serum thyreoglobulin assay with or without 131I scintigraphy and ablation with 131I of remnants in low risk patients), the reimbursement is now allowed for the treatment with radioiodine of iodine-avid loco-regional and distant metastases, in subjects with inability to reach adequate TSH levels and/or severe clinical conditions which could be potentially worsened by other concurrent diseases (history of stroke or transient ischemic attack, severe cardiac disease, renal failure or major psychiatric disorders). The Italian Medicines Agency (AIFA) approved this use (and added this hormone in the special list of drugs regulated by the D.Lgs 648/96) on the basis of a series of scientific evidences, proposed by a "team of experts". In the present paper we illustrate the scientific background of the use of rhTSH (clinical usefulness, economic considerations, aspects related to a better quality of life) that allowed the modification of the reimbursement and how it was made possible in the Italian legislative context.

The papillary thyroid carcinoma (PTC) is the most frequent endocrine cancer and it is the most common thyroid cancer (85-95%). Potential risk factors for the incidence of the PTC include radiation exposure, iodine deficiency, family history of thyroid cancer. The PTC is usually indolent and the prognosis is favourable, with a 10 year survival generally reported to exceed 90%. The palpation and growth of thyroid nodules are the more frequent clinical manifestations of the PTC which can be evaluated by physical examination, neck ultrasound and fine needle aspiration cytology (FNAC). The therapeutic management of PTC includes surgical treatment combined with 131I therapy and life long TSH suppressive thyroid hormone replacement. The external beam radiation can be taken into account in select aggressive tumours. Nevertheless the good prognosis of the PTC, the prevalence of persistence or recurrent disease is not trans-curable. The biomolecular studies can permit to individuate the more aggressive PTC subtypes. A more significant attention of the clinical examination, US and FNAC to the thyroid nodular disease will be able to guarantee a more precocious diagnosis and a radical surgical treatment.

Aims To (a) assess the accuracy of F-18-FDG PET/CT in distinguishing malignant from benign pelvic lesions, compared to transvaginal ultrasonography (TVUS) and (b) to establish the role of whole-body F-18-FDG PET/CT, compared to contrast enhanced computed tomography (CT), in staging patients with ovarian cancer. final pathological staging in 22/32 (69%) patients while CT results were concordant in 17/32 (53%) patients. CT incorrectly down-staged four out of six stage IV patients by missing distant metastasis in the liver, pleura, mediastinum, and in left supraclavicular lymph nodes, which were correctly detected by F-18-FDG PET/CT. Patients Fifty consecutive patients with a pelvic lesion, already scheduled for surgery on the basis of physical examination, TVUS, and serum Ca125 levels, were enrolled in the study. Patients' age ranged between 23 and 89 years (mean 64). All patients underwent TVUS including a colour Doppler study followed by a thorax and abdominal CT scan, and whole-body F-18-FDG PIET/CT within 2 weeks prior to surgery. Histological findings obtained at surgery were taken as the 'gold standard' to compare F-18-FDG PET/CT and TVUS, and F-18-FDG PET/CT vs. CT. When tissue analysis showed ovarian cancer, the accuracy of F-18-FDG PET/CT and CT were compared for the purpose of obtaining a precise staging. Results At surgery, the ovarian lesions were malignant in 32/50 patients (64%) and benign in the remaining 18/50 patients (36%). The sensitivity, specificity, NPV, PPV and accuracy of F-18-FDG PET/CT were 87%,100%, 81 %, 100% and 92%, respectively, compared with 90%, 61%, 78%, 80% and 80%, respectively, for TVUS. In staging ovarian cancer, 18F-FDG PET/CT results were concordant with Conclusion PET/CT with 18F-FDG provides additional value to TVUS for the differential diagnosis of benign from malignant pelvic lesions, and to CT for the staging of ovarian cancer patients. Nucl Med Commun 28:589-595 (c) 2007 Lippincott Williams & Wilkins.

Purpose: Prediction of rectal cancer response to preoperative, neo-adjuvant chemo-radiation therapy (CRT) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches. Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up, but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising tool for monitoring the effect of anti-tumour therapy. The aim of this study was to prospectively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT. Methods: Forty-four consecutive patients with locally advanced (cT3-4) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospective study. Treatment consisted of external beam intensified radiotherapy (50 Gy to the posterior pelvis, 56 Gy to the tumour), chemotherapy (in most cases PVI 5-FU at 300 mg/m2 per day) and, 8-10 weeks later, surgery with curative intent. All patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT. One patient died before surgery because of acute myocardial infarction, and was therefore excluded from further analysis. Semi-quantitative measurements of FDG uptake (SUVmax), absolute difference (ΔSUVmax) and percent SUVmax difference (Response Index, RI) between pre- and post-CRT PET scans were considered. Results were correlated with pathological response, assessed both by histopathological staging of the surgical specimens (pTNM) and by the tumour regression grade (TRG) according to Mandard's criteria (patients with TRG1-2 being defined as responders and patients with TRG3-5 as non-responders). Results: Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%) were classified as responders according to Mandard's criteria (8 TRG1 and 15 TRG2), while the remaining 22 (48.9%) were non-responders (9 TRG3 and 13 TRG4-5). Considering all patients, the mean pre-CRT SUVmax was 15.6, significantly higher than the mean value of 5.4 post CRT (p < 0.001). Nevertheless, when stratifying patients according to response to CRT (using Mandard's criteria), the mean RI was significantly higher in responders than in non-responders (75.9% versus 46.9%,p = 0.0015). Using a 66.2% SUVmax decrease as the cut-off value (identified by ROC analysis) for defining response to therapy, the following parameters were obtained: 79.2% specificity, 81.2% sensitivity, 77% positive predictive value, 89% negative predictive value and 80% overall accuracy. Conclusion: The results suggest the potential utility of FDG-PET as a complementary diagnostic and prognostic procedure in the assessment of neo-adjuvant CRT response of locally advanced rectal cancer. ΔSUV max and RI seem the best predictors of CRT response.

Aim Many patients with ovarian cancer are at high risk of recurrence especially in the 2 years following first-line therapy. CA125 serum levels measurement associated to computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) are currently used during follow-up to detect recurrent disease. Unfortunately, in a relevant percentage of cases all of these traditional imaging techniques provide a significant number of doubtful/equivocal results or turn out negative even in presence of elevated Ca125 levels. Aim of our study was to evaluate sensitivity, specificity and accuracy of 18 F-FDG PET/CT in a group of patients with suspicion of ovarian cancer recurrence. Methods We prospectively evaluated 41 patients with a mean age of 59.4 years who had been previously treated for ovarian cancer with surgery and radio-chemotherapy or radio-chemotherapy alone. Following the performance of traditional radiologic imaging (US, CT, MRI) and Ca125 measurement, all patients underwent additional 18 F-FDG PET/CT. PET/CT results were compared with histologic findings or clinical, laboratory and repeated traditional imaging techniques during subsequent follow-up data. Results Of 41 patients 32 had a positive PET-CT (30 true positive, two false positive) whereas nine a negative PET/CT (five true negative, four false negative). Overall, in our experience 18 F-FDG PET/CT provided a good sensitivity (88.2%), specificity (71.4%) and accuracy (85.4%), superior to that reported in literature for traditional radiologic imaging. Conclusions It can be concluded that 18 F-FDG PET/CT appears to be a useful and accurate tool in disclosing early recurrent ovarian cancer.

Purpose: Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results. Methods: Guidelines from related fields and relevant literature have been considered in consultation with leading experts involved in the management of PPGL. The provided information should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals. Conclusion: Since the European Association of Nuclear Medicine 2012 guidelines, the excellent results obtained with gallium-68 (68Ga)-labelled somatostatin analogues (SSAs) in recent years have simplified the imaging approach for PPGL patients that can also be used for selecting patients for peptide receptor radionuclide therapy as a potential alternative or complement to the traditional theranostic approach with iodine-123 (123I)/iodine-131 (131I)-labelled meta-iodobenzylguanidine. Genomic characterisation of subgroups with differing risk of lesion development and subsequent metastatic spread is refining the use of molecular imaging in the personalised approach to hereditary PPGL patients for detection, staging, and follow-up surveillance.

AIM: The aim of our retrospective study was to assess the usefulness of F-FDG PET/CT in the restaging of clear cell renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Sixty-nine patients (median age = 62 years; range = 36-86 years) affected by clear cell RCC (TNM at staging: T1, 42 patients; T2, 13 patients; T3, 11 patients; T4, 3 patients; Fuhrman grade: G2, 47 patients; G3, 20 patients; G4, 2 patients) underwent whole-body F-FDG PET/CT to restage the disease after nephrectomy for clinical or radiological suspicion of metastases. Areas of abnormal uptake at PET/CT were classified, taking the liver uptake as reference, as follows: 1 = faint uptake, lower than liver; 2 = moderate uptake, equal to liver; and 3 = high uptake, higher than liver. Validation of F-FDG PET/CT results was established by (1) biopsy (23 patients) and (2) other imaging modalities (addressed BS; c.e.CT; MRI; F-fluoride PET/CT; subsequent F-FDG PET/CT), and/or clinical and radiological follow-up of 12 months (46 patients). RESULTS: F-FDG PET/CT was positive in 42 patients and negative in 27 patients. Sixteen patients presented single lesions and 26 patients presented multiple localizations of the disease. On a patient basis, 40 patients resulted true positive, 2 patient false positive, 23 patients true negative, and 4 patients false negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90%, 92%, 91%, 95%, and 85%, respectively. On a lesion basis, PET/CT detected 114 areas of abnormal uptake in 42 positive patients of which 112 resulted to be true positive. FDG uptake of the true positive lesions resulted to be high in 83 cases, moderate in 17 lesions, and finally faint in 12 lesions. CONCLUSIONS: F-FDG PET/CT demonstrated a good sensitivity in the restaging of clear cell RCC. Most of the lesions showed intense activity. According to our results, it seems that the use of F-FDG PET/CT in the restaging of RCC is feasible because the number of false-negative cases is limited.

AIM: The aim of this study was to evaluate the role of C-choline PET/CT in the preoperative evaluation of the nodal involvement of patients with bladder carcinoma (BC) suitable for radical cystectomy and extended pelvic lymph node dissection in comparison with contrast-enhanced CT (CECT) using the pathologic specimen as reference standard. PATIENTS AND METHODS: Twenty-six consecutive patients (69.5 ± 9.3 years; range, 49-84) with histologically proven transitional cell BC were treated with radical cystectomy and pelvic lymph node dissection and were enrolled from April 2011 to January 2013. In all patients, paravesical, internal, eternal, and common iliac nodes as well as obturatory, presacral, preaortic, and precaval lymph nodes (LNs) were dissected up to the origin of the inferior mesentery artery. The areas of the LN dissection were grouped as follow: region A included preaortic and precaval LNs; region B included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the right pelvis; region C included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the left pelvis. C-choline PET/CT and abdominal CECT were used to assess the presence of lymph node metastases on a per patient, region, and lesion analysis using the results of surgical specimens obtained at operation as criterion standard. RESULTS: Seven of 26 patients (26.9%) showed nodal metastases at pathologic analysis. Overall, 844 LNs were evaluated, and 38 of them (4.5%) showed metastatic involvement. On a patient-based analysis, C-choline PET/CT showed a sensitivity of 42% and specificity of 84%, whereas, CECT showed a sensitivity of 14% and specificity of 89%. On a region-based analysis, C-choline PET/CT showed a sensitivity of 11% and specificity of 82%, whereas CECT showed a sensitivity of 5% and specificity of 80%. On a lesion (LN)-based analysis, C-choline PET/CT showed a sensitivity of 10% and specificity of 64%, whereas CECT showed a sensitivity of 2% and specificity of 63%. CONCLUSIONS: C-choline PET/CT could provide additional diagnostic information in preoperative nodal staging of patients with invasive BC in comparison with CECT. A study with a larger population should determine if C-choline PET/CT could be recommended as a routine technique in high-risk patients with BC

Aim The aim of this study was to assess the performance of FDG PET/ceCT simultaneously acquired, contemporary read and finally discussed by the radiologist and the nuclear medicine physician for staging and restaging lung cancer patients. Methods We analysed 17 consecutive patients (7F; 10M; mean age 68). Six patients were in staging, 8 patients were in restaging (1 during therapy, 2 after therapy and 5 during the follow-up) and 2 patients needed to characterise a suspect pulmonary mass. All the patients underwent combined FDG PET/CT and ceCT acquired simultaneously on the same tomograph. The images were read and reported together by the nuclear medicine physician and the radiologist. Results None of the patients had adverse reactions nor complained about the procedure. Thirteen FDG PET/ceCT turned out positive, while 4 were completely negative. Among positive patients, a significant SUV max was detected in all the cases (range 1.8–17.5). In the end, 9 patients had a true positive result, 4 true negative, 3 false positive and 1 false negative. Sensitivity, specificity and accuracy of the combined procedure were 90%, 57% and 76% respectively. In 7/17 patients FDG PET/CT and ceCT were completely concordant. FDG PET/CT provided a significant impact on the final interpretation in 7/17 patients while ceCT had a major impact in 3/17 patients. Discussion This preliminary study shows that FDG PET/ceCT is a feasible technique for lung cancer patients, providing an optimal sensitivity (90%). From our results it is advisable not to include patients without an histological diagnosis of cancer due to possible false positivity of the two methods, significantly reducing specificity. However, a proper patient selection is not easy and the future of this combined test relies essentially on the capacity to early identify only the subjects who would really benefit from both the procedures.

PURPOSE: To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. MATERIALS AND METHODS: We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. RESULTS: Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p

PURPOSE: This study aims to evaluate the role of (11)C-choline PET/CT in patients with biochemical relapse after radical prostatectomy (RP) showing prostate-specific antigen (PSA) values lower than 0.5 ng/mL. METHODS: We performed (11)C-choline PET/CT in 71 consecutive patients previously treated with RP showing PSA values lower than 0.5 ng/mL. (11)C-Choline PET/CT was performed following standard procedure. (11)C-Choline PET/CT-positive findings were validated by transrectal ultrasonography + biopsy, repeated (11)C-choline PET/CT, other conventional imaging modality, and histology. RESULTS: (11)C-Choline PET/CT was true positive in 15/71 (21.1%). (11)C-Choline uptake was observed in pelvic lymph nodes (7/71; 9.9%), in the prostatic bed (7/71; 9.9%), and in bone (1/71; 1.4%). Mean PSA, PSA doubling time (PSAdt), and PSA velocity (PSAvel) values ± SD in (11)C-choline PET/CT-positive patients was 0.37 ± 0.1 ng/mL, 3.4 ± 2.1 months, and 0.05 ± 0.1 ng/mL/yr, respectively. (11)C-Choline PET/CT was false negative in 2 patients and false positive in 1 patient. Among all variables, only PSAdt and the ongoing hormonal treatment were statistically significant in the prediction of a positive (11)C-choline PET/CT at multivariate analysis. CONCLUSIONS: (11)C-Choline PET/CT could be used early after biochemical failure even if PSA values are very low, preferentially in hormonal resistant patients showing fast PSA kinetics. An early detection of the site of relapse could lead to a personalized and tailored treatment.

PURPOSE: This study aimed to prospectively investigate F-FDG PET/CT role for the assessment of sarcoidosis activity and extension in comparison with thoracic high-resolution CT (HRCT) and to evaluate the potential clinical impact of PET/CT findings. Secondary aim was to investigate the changes in cardiac FDG uptake related to the specific preparation before PET/CT. METHODS: We prospectively enrolled biopsy proven sarcoidosis patients consecutively referred for F-FDG PET/CT since January 2010. PET/CT was performed after a fat meal followed by 12-hour fasting and compared with thoracic HRCT results obtained in supine position and clinical follow-up. The impact on the clinical management was recorded.Patterns of cardiac FDG uptake of the study group were compared with a historical population in which PET/CT was performed following standard preparation. RESULTS: A total of 28 patients were enrolled, and 35 PET/CT scans were reviewed. On a scan basis, PET/CT was concordant with HRCT in 16 (45.7%), detecting active disease in 10/16 and no signs of activity in 4/16. PET/CT data had a direct impact on management in 4/16.In 19 (54.3%) discordant scans, PET/CT finding was positive in 14 and negative in 5. PET/CT findings influenced the clinical management in 18/19 cases.Considering all scans, PET/CT information influenced the clinical management of 22 (63%) of 35.Our data suggest that cardiac FDG uptake may vary regardless of the preparation before PET/CT. CONCLUSIONS: F-FDG PET/CT was useful to assess sarcoidosis activity and extension and provided valuable information for the clinical management in a single-step examination. Additional data are needed to better ascertain the optimal patient preparation before image acquisition to improve sensitivity of heart lesions.

PURPOSE: Cu-ATSM is a very promising PET radiopharmaceutical for tumor imaging of hypoxia. One of the advantages of this compound compared with other hypoxia-avid tracers is the high tumor-to-background signal offered, which guaranties facilitated tumor delineation. This study analyzes optimal semiquantitative and quantitative parameters obtained by Cu-ATSM PET/CT in the same cohort of patients with special focus on their correlation to disease outcome. PATIENTS AND METHODS: A prospective recruitment of 18 consecutive patients (M:F, 13:5; mean age, 60.7 years) with locally advanced non-small cell lung cancer (n = 7) or head and neck cancer (HNC) was performed. Each participant received 105 to 500 MBq of tracer according to body size and was scanned in a 3-dimensional mode PET/CT 60 minutes after tracer injection. PET images were reconstructed and visualized on a GE Advanced 4.6 workstation for the definition of semiquantitative and quantitative parameters: SUVmax, SUVratio-to-muscle, hypoxic tumor volume (HTV), and hypoxic burden (HB = HTV × SUVmean). These data were subsequently correlated to disease outcome, expressed in terms of progression-free survival calculated on a follow-up period with a median of 14.6 months. RESULTS: All patients showed a moderately to highly increased uptake of Cu-ATSM in tumor lesions, with a mean SUVmax of 5.2 (range, 1.9-8.3) and mean SUVratio of 4.4 (range, 1.6-6.8). In addition, a broad range of HTV and HB was defined as mean values of 99.3 cm (range, 2.5-453.7 cm) and 301 (4.2-1134), respectively. Receiver operating characteristic analysis identified as reference cutoffs with respect to disease outcome with the following values: SUVmax >2.5 (AUC, 0.57; sensitivity, 88.9%; specificity, 50%), SUVratio ≤4.4 (AUC, 0.60; sensitivity, 50; specificity, 83.3%), HTV >160.7 cm (AUC, 0.61; sensitivity, 55.6%; specificity, 75%), and HB >160.7 (AUC, 0.67; sensitivity, 58.3%; specificity, 83.3%). In our cohort, HB showed a statistically significant difference in terms of mean values on the analysis of variance test with respect to disease progression (P = 0.04). On univariate analysis, Cox regression confirmed these findings and showed a significant correlation to progression-free survival for HB (P = 0.05) and HTV (P = 0.02). CONCLUSIONS: In our cohort, the definition of optimal semiquantitative and quantitative parameters on Cu-ATSM PET/CT seems feasible and in line with previously published data. However, when considering the prognostic role with respect to disease outcome, the more robust parameters are represented by HTV and HB.

Lung cancer (LC) still represents one of the most common tumours in both women and men. PET/CT is a whole-body non-invasive imaging procedure that has been increasingly used for the assessment of LC patients. In particular, PET/CT added value to CT is mainly related to a more accurate staging of nodal and metastatic sites and to the evaluation of the response to therapy. Although the most common PET tracer for LC evaluation is 18F-FDG, new tracers have been proposed for the evaluation of lung neuroendocrine tumours (68Ga-DOTA-peptides, 18F-DOPA) and for the assessment of central nervous system metastasis (11C-methionine). This review focuses on the main clinical applications and accuracy of PET/CT for the detection of non-small cells lung cancer (NSCLC), broncho-alveolar carcinoma (BAC), small cells lung cancer (SCLC), lung neuroendocrine tumours (NET) and solitary pulmonary nodules (SPN).

In the present review article we presented the major technical innovations regarding the diagnosis of NET with PET/CT 68Ga-DOTA-peptides compounds over conventional radiologic and scintigraphic imaging, discussing both the different types of radiopharmaceuticals commercially available, trying to making a comparison on the possible advantages and drawbacks of these radiopharmaceuticals, and providing also some technical recommendations to the radiologists and nuclear physicians for using these new methodology in an appropriate manner in the clinical setting.

Several studies investigated the potential roles of imaging modalities in prostate cancer patients for the evaluation of intra-prostatic disease, stage and restage. However no precise guidelines exist about the use of imaging modalities, in particular about the role of PET/CT hybrid imaging. Considering the results of the literature and our experience, we tried to summarize the main applications of choline positron emission tomography (PET) in prostate cancer patients. The use of choline PET/CT for initial diagnosis and staging is not recommended as a first-line method. Instead the main and important application of choline PET/CT is represented by the restaging of the disease in case of biochemical relapse for the detection of lymph node and distant recurrence. In particular choline PET/CT could play a crucial role as first diagnostic procedure in prostate cancer patients who show a fast growing Prostate Specific Antigen (PSA) kinetics.

PURPOSE: The influence of androgen deprivation therapy (ADT) on (11)C-choline uptake in patients with prostate cancer (PC) has not yet been clarified. The aim of our study was to investigate this issue by means of sequential (11)C-choline positron emission tomography (PET)/CT in patients with recurrent PC. METHODS: We retrospectively studied 14 recurrent PC patients (mean age 67 years, range 55-82) during follow-up after radical prostatectomy (RP) with rising serum prostate-specific antigen (PSA) levels. All patients had undergone at least two consecutive (11)C-choline PET/CT scans: the first (11)C-choline PET/CT before commencing ADT and the second (11)C-choline PET/CT after 6 months of ADT administration. RESULTS: The mean serum PSA level before ADT was 17.0 ± 44.1 ng/ml. After 6 months of ADT administration the PSA value significantly decreased in comparison to baseline (PSA = 2.4 ± 3.1 ng/ml, p < .025). Moreover, before starting ADT, 13 of 14 patients had positive (11)C-choline PET/CT for metastatic spread, while after 6 months of ADT administration in 9 of 14 patients (11)C-choline PET/CT became negative. CONCLUSION: These preliminary results suggest that ADT significantly reduces (11)C-choline uptake in androgen-sensitive PC patients.

AIM: To assess the utility of (11)C-choline PET/CT in the restaging of prostate cancer (PC) patients who showed a single finding on bone scintigraphy (BS) that was classified as equivocal or suspected for metastatic lesion. MATERIALS AND METHODS: A total of 25 PC patients with biochemical failure (mean PSA value 11.1 ng/mL; median value 6.3 ng/mL; range 0.2-37.7 ng/mL) after primary treatment were included in this retrospective study. All of them showed a single lesion on BS reported as suspected for metastatic lesion or as equivocal finding. Patients underwent (11)C-choline PET/CT within 1-4 months from BS. Validation was established by follow-up for at least 6 months. RESULTS: On the basis of biopsy confirmation and/or 6-month follow-up, 22 of 25 patients were classified as positive for the presence of metastatic bone lesions: 13 with a single lesion and 9 with multiple lesions. (11)C-choline PET/CT was positive in 19/25 patients and, on a lesion basis, it showed 50 positive findings. BS results were confirmed in 8/25 (32%) patients. (11)C-choline PET/CT detected multiple sites of relapse in 11/25 (44%) patients: in 2/11, a single bone lesion associated with other extraosseous sites of relapse; in 6/11, multiple bone lesions; in 3/11, multiple bone lesions and other extraosseous localizations. Finally, 6/25 patients were negative on (11)C-choline PET/CT. In 3/6 patients, an osteoblastic lesion was seen on CT attenuation correction images (PET false negative; BS true positive), while in 3/6 patients only findings suggestive of the presence of degenerative disease were found (PET true negative; BS false positive). On a patient basis, (11)C-choline PET/CT showed a diagnostic sensitivity of 86% (19/22) and a specificity of 100% (19/19). CONCLUSIONS: In our study, (11)C-choline PET/CT detected unknown lesions in 11/25 patients. Patients with a single equivocal finding on BS could have important additional information from (11)C-choline PET/CT study, especially in the detection of additional metastases, to choose an appropriate treatment

This study reports on our experience with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric patients affected by Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). We studied 20 pediatric subjects (12 males, 8 females; mean age, 10 years; range, 6 months to 14 years) with malignant lymphoma (9 HD, 11 NHL) for a 4-year period of time. Overall, 45 PET scans were performed: 7 at disease presentation and 38 for evaluation of response to therapy or follow-up study. All PET results were compared with conventional imaging (CI), mainly computed tomography (CT) and/or magnetic resonance imaging (MRI), and supported by clinical follow-up and/or histologic data. In 18 of 20 patients, PET findings correctly identified the status of disease. Two (2) subjects (respectively, 1 HD and 1 NHL, both at follow-up) resulted falsely positive: 1 due to prominent thymic uptake, and the other due to nonspecific inflammation. Of 45 scans, PET findings were consistent with clinical follow-up and other CI data in 43 cases (16 true-positive and 27 true-negative results) and resulted falsely positive in the remaining 2 scans. On a lesion-by-lesion basis (overall, 153 lesions: 84 nodal and 69 extranodal), we found a concordance between CI and PET findings in 25 nodal (29.8%) and in 22 extranodal sites (32%). PET was more accurate than CI, as it identified active disease in 1 patient negative at CI and excluded relapse in 6 patients with inconclusive CI and in 2 patients with a falsely positive CI. Overall, PET sensitivity and specificity was 100% and 93% versus 94% sensitivity and 72.4% specificity for CI. This comparative study shows FDG PET to be more accurate than CI in evaluating children with lymphoma. Our data also confirms that (18)F-FDG PET may show false-positive findings.

AIM To evaluate clinical efficacy of a dual-time acquisition protocol, which included 4 and 20/24-h imaging with antigranulocyte antibody scintigraphy (LeukoScan) combined with semiquantitative analysis in the diagnosis of infection in painful hip prosthesis. METHODS Sixty-seven consecutive patients with hip prosthesis were enrolled in this research project: 35 females, 32 males, mean age of 56.3 years. All patients had clinical and biochemical suspicious of infection. Each prosthesis had been implanted 3 months to 12 years before enrollment in this study. Twenty-four patients were on antibiotic therapy at the time of scintigraphy. Seven patients had bilateral hip prosthesis, one painful and the other painless: the seven painless prostheses were considered controls. LeukoScan examination was performed both at early (4 h) and delayed (20/24 h) times. The scintigraphic data were assessed both by visual and semiquantitative methods by three experienced nuclear medicine physicians blinded to clinical, laboratory and radiographic results. The uptake was graded visually by a 4-point scale: intense=3, moderate=2, mild=1 and absent=0. The semiquantitative analysis was obtained by a region of interest (ROI) analysis used in the anterior views to measure the ratio between the mean radioactivity in the prosthesis and the background radioactivity in the early and delayed images. An increase in the intensity of uptake of at least one scale-step at visual analysis and 20% at semiquantitative ROI analysis at the dual-time (early vs. delayed) LeukoScan was considered consistent with infection, whereas a stable or decreasing pattern was judged a negative result. Three-phase 99mTc-hydroxymethane diphosphonate bone scan was also performed routinely. Final diagnosis was determined at surgery and/or long-term clinical and imaging follow-up. RESULTS At visual analysis, sensitivity for both early and delayed imaging was 94%, whereas specificity was 71% for early imaging and 83% for early and delayed imaging approach. At semiquantitative ROI analysis, sensitivity remained 94%, whereas specificity rose slightly to 73% for early imaging and to 90% for early and delayed imaging combined. Of note, four false-positive early scans were diagnosed correctly as negative on delayed imaging showing a decreasing pattern in uptake intensity. Sensitivity and specificity were similar whether patients were on or off antibiotic therapy. CONCLUSION Our data show that early imaging LeukoScan is highly sensitive in evaluating septic prosthesis, but it is not optimally specific. Although the dual-time LeukoScan is capable of significantly increasing specificity for detecting infection. The semiquantitative ROI analysis further increased the specificity. Concomitant antibiotic treatment did not seem to influence the diagnostic efficacy of LeukoScan scintigraphy in detecting infected hip prosthesis.