Esperienza preliminare con 18F-Florbetapir nella valutazione PET/TC del paziente con deficit cognitivo

BACKGROUND: Pathologic deposition of amyloid β (Aβ) protein is a fundamental component in the pathogenesis of Alzheimer’s disease (AD). PET ligands for Aβ protein are increasingly used in diagnosis and research of dementia syndromes. Here, we report a preliminary experience about PET study using 18F-florbetapir in patients with AD and Mild Cognitive Impairment (MCI) . METHODS: Twenty cognitively impaired patients (mean age ± SD, 72 ± 7.5) were recruited for the study. At the enrolment and after a year of follow-up, all patients underwent detailed clinical and neuropsychologic assessment using Alzheimer’s Disease Assessment Scale-Subscale Cognitive (ADAS- Cog) and Mini Mental State Examination (MMSE). All participants underwent dynamic 18F-florbetapir PET on a high-resolution research tomography. Static PET images were dichotomically (positive or negative ) evaluated by four trained raters masked to clinical status. The “majority” interpretation was made. The concordance among the four different interpretations was performed using Fleiss’s Kappa. Also concordances between the “majority” interpretation (MI) and cognitive tests, and MI and final clinical diagnosis were performed applying Cohen’s Kappa. Finally paired t test and Wilcoxon signed rank test were applied to estimate the statistic difference between initial and final ADAS-Cog and initial and final MMSE. RESULTS A statistic difference between initial and final MMSE (95% CI: 1,16 – 6,24, t(19) = 3,05, p-value = 0,003274; Wilcoxon signed rank: p-value = 0,0004529) and initial and final ADAS-Cog (paired t test: 95% CI: 0,06 – 7,24, t(19) = 2,13, p-value = 0,02344; Wilcoxon signed rank: p-value = 0,03173) was found. Among raters Fleiss’s Kappa value was 0.583, Cohen’s Kappa was good both between the MI and cognitive tests (MI/ADAS-Cog Cohen’s Kappa=0,737 and MI/MMSE Cohen’s Kappa=0,615) and with final clinical diagnosis (Cohen’s Kappa= 0,737) CONCLUSIONS: 18F-florbetapir seems to be a safe and useful radiotracer to detect cerebral Aβ deposits, with a good concordance among trained raters and between PET’s results and clinical data

Studio pilota per un nuovo protocollo combinato di terapia in paziente con adenocarcinoma prostatico ormonorefrattario metastatico: docetaxel e 153 Sm-EDTMP.

Background Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). 153Sm-EDTMP has been approved for palliation of painful skeletal metastases. We investigated the possible synergistic effect on tumor response and survival of 153Sm-EDTMP and a taxane-based chemotherapy regimen, that represents the standard of care for this stage of disease. Methods Thirty HRPC patients were enrolled, with a mean age of 70 years. All patients had metastatic bone disease; the extent of bone involvement was evaluated by means of a new bone scan scoring system. All patients received 153Sm-EDTMP (37 MBq/kg i.v.) first; Docetaxel (75 mg/sqm i.v. every 21 days) was administered after recovery of marrow toxicity. Results More than 70% of patients showed some response to treatment (complete response+partial response+stable disease). Mean time-to-progression was 8 months, while overall survival had a median of 18 months, and until 30th May 2009 five patients are still alive. Haematological toxicity observed both after 153Sm-EDTMP and Docetaxel was acceptable: only one patient showed G4 leucopoenia, one patient presented a G4 neutropoenia, and five G3 neutropoenia, all of them after 153Sm-EDTMP; after Docetaxel only one patient showed G3 anemia. We did not find a statistically significant correlation between bone lesions (using bone scan scoring system) and clinical results. The mild increase of the mean scan score after treatment most likely reflects the state of increased bone remodelling, in the perspective of a global stability of illness. Conclusion The results of this study confirm that 153Sm-EDTMP and Docetaxel in combination are effective on tumor response and overall survival, although inducing moderate haemopoytic toxicity. This work provides the rationale for further investigations regarding the combined therapeutic strategies

Sentinel lymph node mapping in breast cancer: a critical reappraisal of the internal mammary chain issue

Although, like the axilla, the internal mammary nodes (IMNs) are a first-echelon nodal drainage site in breast cancer, the importance of their treatment has long been debated. Seminal randomized trials have failed to demonstrate a survival benefit from surgical IMN dissection, and several retrospective studies have shown that IMNs are rarely the first site of recurrence. However, the recent widespread adoption of sentinel lymph node (SLN) biopsy has stimulated a critical reappraisal of such early results. Furthermore, the higher proportion of screening-detected cancers, improved imaging and techniques (i.e., lymphoscintigraphy for radioguided SLN biopsy) make it possible to visualize lymphatic drainage to the IMNs. The virtually systematic application of adjuvant systemic and/or loco-regional radiotherapy encourages re-examination of the significance of IMN metastases. Moreover, randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic chemotherapy, which was not routinely administered in the earlier studies. However, the contribution from IMN treatment is unclear. Lymphoscintigraphic studies have shown that a significant proportion of breast cancers have primary drainage to the IMNs, including approximately 30% of medial tumors and 15% of lateral tumors. In the few studies where IMN biopsy was performed, 20% of sentinel IMNs were metastatic. The risk of IMN involvement is higher in patients with medial tumors and positive axillary nodes. IMN metastasis has prognostic significance, as recognized by its inclusion in the American Joint Committee on Cancer staging criteria, and seems to have similar prognostic importance as axillary nodal involvement. Although routine IMN evaluation might be indicated, it has not been routinely performed, perhaps because IMN drainage with lymphoscintigraphy is more difficult to demonstrate than axillary drainage. This difference is due to technical reasons and not the absence of lymphatics to the IMN. Recent anatomical studies have confirmed a model of breast lymphatic drainage that comprises superficial, deep and perforating systems. The superficial system drains to the axilla, usually to a lymph node posterior to the pectoralis minor muscle. The deep system drains to the axilla and also anastomoses with the perforating system which drains to the IMNs. The perforating system does not connect with the superficial system. The prevalence of IMN drainage tends to reflect the method of lymphoscintigraphy, where peritumoral (deep lymphatic system) injections have a much higher likelihood of IMN drainage than subareolar or subdermal (superficial lymphatic system) injections. The fused SPECT/CT images represent a further technical solution to increase the identification of IMNs and consequently can significantly reduce the false negative rate of sentinel lymph node biopsy. Before mature results from current and future randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy and IMNs biopsy may be used to guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity

Sentinel lymph node biopsy of oral/oropharyngeal squamous cell carcinoma: Techniques, indications, advantages, and accuracy

No abstract availabl

Sentinel node mapping in melanoma of the back: SPECT/CT helps discriminate "True" and "False" in-transit lymph nodes

A 32-year-old man with melanoma on the right paramedian region of the lower back underwent lymphoscintigraphy for radioguided sentinel node (SN) biopsy. Planar imaging showed the presence of 2 sites of radioactivity accumulation corresponding to an axillary SN and to an "in-transit" SN, located on the right side of the upper trunk. A further "hot spot" placed on the left paramedian region of the lower back was identified by planar lymphoscintigraphy. This last finding could be mistaken for another "in-transit" SN, but SPECT/CT demonstrated it was actually a nonspecific radiopharmaceutical accumulation at the level of the right renal pelvis

Radium 223 dichloride: A multidisciplinary approach to metastatic castration-resistant prostate cancer

The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were β-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor type

Radioguided occult lesion localization technical procedures and clinical applications

Purpose: Regarding radioguided surgery, the concept of “radioguided occult lesion localization” (ROLL) is based on both preoperative interventional imaging and intraoperative radioguided detection of a clinically occult neoplastic lesion. Methods: This methodology consists in the direct administration into the lesion of99mTc–macroaggregated human albumin formed by relatively large particles retained at the injection site, which direct radioguided excisional biopsy. Results: This modality has expanded from the classic application of ROLL for nonpalpable breast lesions to other tumors, such as solitary pulmonary nodules or recurrences from differentiated thyroid carcinoma. In 2011, in order to improve the classification of different radioguided surgical procedures, ROLL applications were included in the more complete concept of GOSTT (Guided intraOperative Scintigraphic Tumor Targeting). This concept was introduced to include the entire range of basic and advanced radioguided procedures necessary to supply a “road map” for the surgeon. Conclusions: The terms ROLL and GOSTT have further developed by incorporating novel modalities such as hybrid tracers for simultaneous fluorescence and radioactive signal detection and innovative navigation systems based on mixed-reality protocols

Sentinel lymph node mapping in melanoma: The issue of false-negative findings

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

Novel Experience in Hybrid Tracers: Clinical Evaluation of Feasibility and Efficacy in Using ICG-99mTC Nanotop for Sentinel Node Procedure in Breast Cancer Patients

The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (Tc Nanotop) for SLN biopsy (SLNB) in breast cancer patients

Sentinel Lymph Node Biopsy in Breast Cancer: Indications, Contraindications, and Controversies

Axillary lymph node status, a major prognostic factor in early-stage breast cancer, provides information important for individualized surgical treatment. Because imaging techniques have limited sensitivity to detect metastasis in axillary lymph nodes, the axilla must be explored surgically. The histology of all resected nodes at the time of axillary lymph node dissection (ALND) has traditionally been regarded as the most accurate method for assessing metastatic spread of disease to the locoregional lymph nodes. However, ALND may result in lymphedema, nerve injury, shoulder dysfunction, and other short-term and long-term complications limiting functionality and reducing quality of life. Sentinel lymph node biopsy (SLNB) is a less invasive method of assessing nodal involvement. The concept of SLNB is based on the notion that tumors drain in an orderly manner through the lymphatic system. Therefore, the SLN is the first to be affected by metastasis if the tumor has spread, and a tumor-free SLN makes it highly unlikely for other nodes to be affected. Sentinel lymph node biopsy has become the standard of care for primary treatment of early breast cancer and has replaced ALND to stage clinically node-negative patients, thus reducing ALND-associated morbidity. More than 20 years after its introduction, there are still aspects concerning SLNB and ALND that are currently debated. Moreover, SLNB remains an unstandardized procedure surrounded by many unresolved controversies concerning the technique itself. In this article, we review the main indications, contraindications, and controversies of SLNB in breast cancer in the light of the most recent publications