[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Management of cutaneous melanoma has changed after introduction in the clinical routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the nodal basin status, SLNB provides a powerful prognostic information. Nevertheless, some debate still surrounds the accuracy of this procedure in terms of false-negative rate. 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. In this review, we identified all the technical aspects that the nuclear medicine physician, the surgeon, and the pathologist should take into account to improve accuracy of the procedure and minimize the false-negative rate. In particular, SPECT/CT imaging detects more SLNs than those found by planar lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a consensus on the radioactive counting rate threshold to better guide the surgeon in identifying the lymph nodes with the highest likelihood of housing metastases ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques is also a further potential source for error. More accurate SLN analysis (eg, molecular analysis by reverse transcriptase-polymerase chain reaction) and more extensive SLN sampling identify more positive nodes, thus reducing the false-negative rate.The clinical factors identifying patients at higher-risk local recurrence after a negative SLNB include older age at diagnosis, deeper lesions, histological ulceration, and head-neck anatomic location of the primary lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma patients remains controversial, because the majority of studies have failed to demonstrate overall statistically significant disadvantage in melanoma-specific survival for false-negative SLNB patients compared with true-positive SLNB patients.When new more effective drugs will be available in the adjuvant setting for stage III melanoma patients, the implication of an accurate staging procedure for the sentinel lymph nodes will be crucial for both patients and clinicians. Standardization and accuracy of SLN identification, removal, and analysis are required.
Clinical nuclear medicine 02/2014; · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to establish the clinical value of F-DOPA PET/CT in patients with adrenal and extra-adrenal paragangliomas (PGLs).
Twenty-six consecutive patients with suspected or recurrent PGL underwent MR (and/or CT) and F-DOPA PET/CT. Histopathology confirmation was obtained in 20 cases. Genetic analysis on known susceptibility genes for PGL (VHL, RET, SDHx, TMEM127) was available in 13 patients.
Fourteen patients were affected by PGL (8 with head/neck location, 6 with abdominal/thoracic location), whereas 12 showed masses of other origin. Three patients proved to be SDHD, 1 SDHB, 2 SDHC, and 1 TMEM127 mutation carriers. F-DOPA PET/CT showed pathological uptake in 13 of 26 patients. The procedure identified all PGLs except one with bone metastases (previous malignant adrenal PGL). No uptake was found in patients without proven PGL. Thus, in the whole group, F-DOPA PET/CT sensitivity was 92.8%, and specificity was 100% with positive and negative predictive values of 100% and 92.3%, respectively. Total diagnostic accuracy was 96.2%. In the head/neck subgroup, sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 100%. In the abdominal location, sensitivity was 80% and specificity was 100%, and positive and negative predictive values were 100% and 91.7%, respectively. Abdominal diagnostic accuracy was 93.7%. Radiotracer uptake was superimposable in head/neck PGLs versus abdominal PGLs and in mutated versus wild-type patients.
The high diagnostic performance of F-DOPA PET/CT showed this technique to be a useful tool in detecting PGLs, above all those located at the head/neck site, regardless of the genetic pattern.
Clinical nuclear medicine 12/2013; · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the field of nuclear medicine, multiagent imaging can disclose enhanced expression of specific target molecules of neoplastic cells. This molecular information can be combined with the information provided by anatomical imaging. Over the past 20 years the use of radiolabeled somatostatin analogs as high-affinity tracers binding specifically to somatostatin receptors has allowed successful molecular imaging of neuroendocrine neoplasms (NENs), initially with single-photon-emitting radiopharmaceuticals, and subsequently also with positron-emitting radiopharmaceuticals. In this context, whole-body somatostatin receptor scintigraphy has changed the diagnostic and therapeutic approach to patients with NENs; moreover, somatostatin analog positron emission tomography (PET) tracers that allow higher spatial resolution imaging have recently been introduced. Nevertheless, several NENs can also be successfully imaged with radioagents that target the catecholamine pathway. Although radioiodinated meta-iodobenzylguanidine (MIBG) is traditionally the first option for radionuclide imaging and treatment of these NENs, the use of PET with 18F-l-dihydroxyphenylalanine is being increasingly reported, this approach showing several advantages over conventional imaging. Moreover, changes in tumor biology can be characterized by modifications in receptor or transporter expression on the cell membrane, and evidence has recently emerged that NENs expressing glucose transporters are more aggressive than tumors with low expression of glucose transporters. Therefore, [18F]FDG PET could provide prognostic information useful for stratifying patients according to their risk and for planning the correct therapy. The identification of new radiopharmaceuticals specific for different targets will constitute the basis not only of new diagnostic imaging approaches, but also of new therapeutic applications in NENs, besides radiolabeled peptide receptor radionuclide and 131I-MIBG therapy.
Clinical and Translational Imaging. 01/2013; 1(6).
[Show abstract][Hide abstract] ABSTRACT: Bone metastases are responsible for most of the morbidity and mortality associated with solid malignant tumors, occurring in about 65-70% of the patients with advanced breast or prostate cancer. The pathophysiology of skeletal metastasis is a complex process that involves several biologic process leading to cellular invasion, adhesions and stimulation of osteoclasts and osteoblasts with the mediation of several factors including cytokines, serine proteases and tumor-derived factors. The clinical management of pain from bone metastasis, which is mostly due to indirect stimulation of sensory nerve endings by cytokines and other biologically-active compounds released locally in response to the presence of tumor cells in the bone marrow, includes several options that can be used either alone or in varying combinations, such as analgesic drugs, chemo- or hormonal therapy, bisphosponates, external beam radiation therapy, and surgery. Bone-seeking radiopharmaceuticals play an important role in the treatment of pain caused by multiple blastic or mixed-type skeletal lesions; they have in general a favorable toxicity profile and a high rate of overall clinical benefit, although they may differ in terms of duration of pain palliation and suitability for repeat treatments. The palliative effect can be attributed to the radiation targeted to the bone marrow space, and the overall average response ranges between about 45-80%, with complete response in 10-30% of the cases. In selected clinical conditions, radionuclide therapy can also constitute an effective systemic treatment beyond bone pain palliation, and a synergistic anti-tumour effect can be expected by the combination with other agents, such as chemotherapy or bisphosphonates. This review summarizes the current experience with bone-seeking radiopharmaceuticals used for bone pain palliation, focusing on indications, patients' selection, efficacy and toxicity. Finally, the available data on combination therapies showing encouraging results as to potential anti-tumor efficacy are also reviewed.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 08/2011; 55(4):431-47. · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Resumen.Los informes de autopsia relatan la ocurrencia de metástasis óseas hasta en el 70% de los pacientes con cáncer de mama o de próstata. La localización preferencial de metástasis óseas en el esqueleto axial es probablemente debida al flujo sanguíneo en la médula ósea (especialmente abundante en el esqueleto axial) y al hecho de que la sangre venosa de la pelvis o mama a través del plexo venoso vertebral (circulación de Batson) representan factores de riesgo predisponentes para la siembra del tumorAbstract.Autopsy-based studies report the occurrence of skeletal metastases in up to 70% of the patients with breast or prostate cancer. Common localization of bone metastases in the axial skeleton is probably due to sluggish blood flow in the red marrow (which is particularly abundant in the axial skeleton) and to the fact that venous blood from the pelvis or breast flows through the vertebral-venous plexus (Batson circulation); both these occurrences represent predisposing conditions for tumor seeding
[Show abstract][Hide abstract] ABSTRACT: The early diagnosis of non-palpable breast cancer is the object of recent developments in the imaging procedures employed for screening purposes. In some patients, the presence of microcalcifications (MC) is the only indication of tumor. Although X-ray mammography (MRx) has high sensitivity in detecting MC, its specificity is however too low for diagnostic purposes. The aim of this study was to compare (99m)Tc-sestamibi scintimammography (SMM) and MRx in the differential diagnosis between benign and malignant clusters of MC and to assess the possible incremental value of SMM on specificity.
A total of 283 consecutive women (mean age 53+/-8 years) with MC identified on X-ray mammograms underwent SMM. Scintigraphic images were acquired 10 minutes after the i.v. injection of (99m)Tc-sestamibi (740 MBq). Planar images of both breasts were simultaneously obtained in the lateral prone position and in the anterior and oblique projections using a dual head camera. Sixty-nine women underwent surgery, whereas the remaining 214 patients had completely negative follow-up for 5 years (a 5-year follow-up period is considered the "gold standard" for diagnosing benign lesions).
Histology demonstrated 32/69 primary breast carcinomas (prevalence of disease: 11% of all the 283 patients) and 37/69 benign lesions. The receiver operating characteristic (ROC) statistical technique was employed to compare the diagnostic value of Mrx alone to that of combined MRx and SMM. The detected difference between the areas under the MRx ROC curve (area=0.72, standard error 0.052) and the MRX and SMM ROC curve (area=0.86, standard error 0.039) was statistically significant (p<0.01). Moreover, the combination of MRx and SMM provided a significant improvement of the negative predictive value (NPV=98%) for MC with low-suspicion of malignancy at MRx.
SMM can be considered as a complementary tool in the pre-operative work-up of patients with breast lesions. Furthermore, the high negative predictive value of this technique, makes it especially valuable in the perspective of reducing the number of negative breast biopsies or unnecessary surgical interventions.
Anticancer research 10/2009; 29(10):4251-7. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anaplastic thyroid cancer (ATC) is a rare aggressive tumor arising from the follicular cells of the thyroid gland (as does well differentiated thyroid cancer, WDTC), but ATC cells do not retain any of the biological features of the original follicular cells, such as uptake of iodine and synthesis of thyroglobulin. Prognosis is almost invariably fatal. In this article the Authors review the pathology, epidemiology, clinical presentation, diagnosis and treatment options of ATC. ATC incidence typically peaks at the 6-7th decade of life (mean age at diagnosis 55-65 years), women representing 55-77% of all patients. ATC represents 2-5% of all thyroid tumors, with a decreasing trend with respect to the incidence of WDTC. The histologic patterns of ATC include giant-cell, spindle-cell and squamoid-cell tumors; these subtypes frequently coexist and are not predictive of patients' outcome. Immuno-cyto-chemistry for thyroglobulin is usually negative or weakly positive and some cases are also negative for keratin, particularly in the spindle-cell areas. ATC may arise de novo, but in most cases it develops from a pre-existing WDTC, especially the follicular subtype. Most ATC patients complain of local compressive symptoms, such as dysphagia, dysphonia, stridor and dyspnea in addition to neck pain and tenderness; in over 70% of the patients the tumor infiltrates surrounding tissues, such as fat, trachea, muscle, esophagus, and larynx. The clinical course of a rapidly enlarging mass that is firm and fixed to surrounding structures in an elderly patient is quite suggestive for ATC. Diagnosis can be confirmed by fine needle aspiration cytology or, in doubtful cases, by histology on core biopsy. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are useful for defining the local extent of disease and for identifying distant metastases, as is also positron-emission tomography (PET) with [(18)F]FDG. Tracheoscopy and esophagoscopy should be performed every two months, or whenever patients refer the appearance or worsening of local symptoms. Bone scintigraphy may be included in the follow-up of patients with a longer survival and relatively good health. Because of its aggressive behavior, the latest American Joint Committee on Cancer Staging Manual classifies all ATCs as T4 and Stage IV tumors, regardless of their actual overall tumor burden. Treatment of ATC has not been standardized because it is not clear whether or not therapy is effective in prolonging survival; most patients die within six momths from diagnosis, primarily because of asphyxiation caused by local tumor invasion. When employed alone, surgery, radiotherapy, or chemotherapy are seldom adequate to achieve overall control of the disease, but a combination of these treatments may improve local control. Surgical treatment of local disease offers the best opportunity for prolonged survival if the tumor is intrathyroidal. When the tumor is extrathyroidal, the surgical approach to ATC is controversial. Some favourable results have recently been reported with newly developed chemotherapy agents and hyper-fractioned radiation therapy. Tracheostomy should be performed in patients with impending airway obstruction when death is not imminent from other sites of disease, and if patients are not candidates for local resection or chemoradiation. Interventional bronchoscopy, including Nd-YAG laser and airways stenting are alternatives to surgery in inoperable ATC-induced tracheal obstruction. Gene therapy is under investigation. Although very rare, ATC is a highly aggressive tumor that belongs to the group of killer tumors with median survival time not longer than 6-8 months. Surgery, chemotherapy and radiotherapy are the conventional therapeutic strategies performed in the attempt to improve survival. Unfortunately, very often they do not succeed any clinical benefit but only palliative RESULTS: New therapeutic strategies based on molecular approaches are desirable.
[Show abstract][Hide abstract] ABSTRACT: Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of 153Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy.
Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was <or=10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with 153Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after 153Sm-EDTMP (14 patients, group B) or within 1 month after 153Sm-EDTMP (16 patients, group C).
Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either 153Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both 153Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by 153Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of 153Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008).
The results of this study confirm that 153Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies.
European journal of nuclear medicine and molecular imaging 08/2007; 34(7):1023-30. · 5.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite vast worldwide experience in the use of 131I for treating Graves' disease (GD), no consensus of opinion exists concerning the optimal method of dose calculation. In one of the most popular equations, the administered (131)I dose is directly proportional to the estimated thyroid gland volume and inversely proportional to the measured 24-hour radioiodine uptake. In this study, we compared the efficiency of different tissue-absorbed doses to induce euthyroidism or hypothyroidism within 1 year after radioiodine therapy in GD patients. The study was carried out in 134 GD patients (age, 53 +/- 14 year; range, 16-82 year; thyroid volume, 28 +/- 18 mL; range, 6-95 mL; average 24-hour thyroid uptake, 72%) treated with (131)I therapy. The average radioiodine activity administered to patients was 518 +/- 226 MBq (range, 111-1110). The corresponding average thyroid absorbed dose, calculated by a modified Medical Internal Radiation Dose (MIRD) equation was 376 +/- 258 Gy (range, 99-1683). One year after treatment, 58 patients (43%) were hypothyroid, 57 patients (43%) were euthyroid, and 19 patients (14%) remained hyperthyroid. The patients were divided into 3 groups: 150 Gy (n = 32), 300 Gy (n = 58) and >300 Gy (n = 44). No significant difference in the rate of recurrent hyperthyroidism was found among the 3 groups (150 Gy: 15%; 300 Gy: 14%; and > or =300 Gy: 14%; chi-square test, p = 0.72). Whereas, the rate of hypothyroidism in the 3 groups was significantly correlated with the dose (150 Gy: 30%; 300 Gy: 46%; >300 Gy: 71%; chi-square test, p = 0.0003). The results obtained in this study show no correlation between dose and outcome of radioiodine therapy (in terms of persistent hyperthyroidism) for thyroid absorbed doses > or =150 Gy, while confirming the relation between the thyroid absorbed dose and the incidence of hypothyroidism in GD patients.
Cancer Biotherapy and Radiopharmaceuticals 04/2005; 20(2):218-23. · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Both clinical and subclinical thyrotoxicosis can result from a wide range of disorders. Establishing the correct etiology underlying thyrotoxicosis is essential to direct treatment towards its specific pathophysiologic process. Based on clinical experience and guideline recommendations, radioiodine iodine uptake (RAIU) measurement and scintigraphy are often requested as the first-line investigation in thyrotoxic patients; however, their specific individual contribution to the differential diagnosis of thyrotoxicosis has not been previously investigated. In our study we aimed at evaluating the diagnostic role of RAIU measurement and scintigraphy in the management of thyrotoxicosis. A total of 108 patients with clinical and 42 patients with subclinical thyrotoxicosis were included in this retrospective study. All patients had RAIU measured at 24 hours after (131)I-iodide administration, followed by thyroid scintigraphy. Based on the combination of RAIU and scintigraphy, patients were classified as having diffuse toxic goiter (DTG) in 44% (the most common diagnosis), toxic adenoma in 15.9%, thyroiditis in 14%, and toxic multinodular goiter in 2.7%, while the pattern was inconclusive in 22.7% of all patients. When considering only patients with clinical thyrotoxicosis, the scan was inconclusive in 12.9% of patients whereas it was inconclusive in 47.6% of patients with subclinical thyrotoxicosis. There was a highly significant association between thyrotoxic status and scan result, with a statistically significant better performance of RAIU and scintigraphy in patients with clinical thyrotoxicosis when compared to patients with subclinical thyrotoxicosis considered as a whole (P<0.001). Instead, no statistically significant difference was observed between patients with subclinical thyrotoxicosis and TSH <0.1 mU/L and patients with TSH between 0.1 mU/L and 0.4 mU/L (P=0.191). In conclusion, we confirm the key role of RAIU and scintigraphy in the management of thyrotoxicosis and document its better performance in patients with clinical thyrotoxic status.
Hellenic journal of nuclear medicine 13(2):132-7. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Il presente capitola riguarda alcuni dei parametri pratici più importanti che devono essere impostati quando si esegue un’acquisizione
con la gamma-camera. A causa delle differenze tra le varie ditte, non saranno trattati gli aspetti tecnici legati ai sistemi
di correzione per l’attenuazione mediante sorgente trasmissiva gamma o mediante TC. Per maggiori dettagli operativi sulle
modalità di verifica dei corretti parametri di acquisizione, si rimanda al successivo Capitolo 11.
[Show abstract][Hide abstract] ABSTRACT: I reni sono situati nello spazio retroperitoneale ai lati del muscolo psoas, all’altezza del tratto D11-L3 della colonna vertebrale,
a circa 7 cm di profondità dal piano posteriore. Hanno forma “a fagiolo”, con il lato concavo rivolto medialmente e anteriormente;
presentano un asse maggiore approssimativamente di 12 cm, e formano un angolo di circa 20 gradi aperto verso il basso, sul
piano frontale. L’ilo, attraverso il quale passano vasi, nervi, linfatici e bacinetto, si trova al centro del lato concavo.
Il parenchima renale presenta due distinte zone: la corticale, periferica, che contiene i glomeruli e i tubuli contorti prossimali
e distali e, con le colonne del Bertin, si approfonda nella midollare fino all’ilo; la midollare, interna, che contiene le
restanti parti del sistema tubulare, rappresentata dalle piramidi, le cui basi sono rivolte verso la corticale, mentre gli
apici guardano verso l’ilo formando le papille renali che aggettano nei calici. Ogni rene è costituito dai lobi renali, unità
funzionali anatomicamente distinte ma fuse tra loro; in ogni rene sono presenti da 5 a 14 lobi, ciascuno dei quali è formato
da una massa centrale conica di sostanza midollare (piramide) circondata, eccetto che a livello della papilla, da uno strato
di tessuto corticale (Fig. 22.1).
Fig. 22.1 Anatomia macroscopica del rene