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Biomedical subjects

G Paganelli

Publications and source records attributed to G Paganelli.

At least 19 recordsLinked to original sources

A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases.

BACKGROUND: Sentinel node biopsy (SNB) has become a standard treatment in staging axillary lymph nodes in early breast cancer. SNB, however, is an invasive procedure and is time-consuming when the sentinel node is analysed intra-operatively. Breast cancer is frequently characterised by increased 2-fluoro-2-deoxy-D-glucose uptake and many studies have shown encouraging results in detecting axillary lymph node metastases. The aim of this study was to compare SNB and -positron emission tomography (-PET) imaging, to assess their values in detecting occult axillary metastases. PATIENTS AND METHODS: In all, 236 patients with breast cancer and clinically negative axilla were enrolled in the study. 18-FDG-PET was carried out before surgery, using a positron emission tomography (PET)/computed tomography scanner. In all patients, SNB was carried out after identification through lymphoscintigraphy. Patients underwent axillary lymph nodes dissection (ALND) in cases of positive FDG-PET or positive SNB. The results of PET scan were compared with histopathology of SNB and ALND. RESULTS: In all, 103 out of the 236 patients (44%) had metastases in axillary nodes. Sensitivity of FDG-PET scan for detection of axillary lymph node metastases in this series was low (37%); however, specificity and positive predictive values were acceptable (96% and 88%, respectively). CONCLUSIONS: The high specificity of PET imaging indicates that patients who have a PET-positive axilla should have an ALND rather than an SNB for axillary staging. In contrast, FDG-PET showed poor sensitivity in the detection of axillary metastases, confirming the need for SNB in cases where PET is negative in the axilla.

Adult↗

Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept.

PURPOSE: Cervical lymph node status is the most important pathological determinant of prognosis and decision making in head and neck squamous cell carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy (LS) can supply a complete map of the lymphatic drainage before surgery, allowing planning of the type of intervention and serving to guide lymphadenectomy. METHODS: The study population comprised 14 patients with T2-4 SCCs of the tongue and clinically negative lymph nodes in the neck (cN0) who were scheduled to undergo tumour resection and selective level I-IV neck dissection extended to level V. LS was performed in all patients following the injection of (99m)Tc-colloidal sulphide in three aliquots around the primary lesion. Dynamic, static and tomographic images of the head and neck were acquired. The operative specimens were subjected to lymphoscintigraphic evaluation. Preoperative and postoperative imaging results were compared with the pathological findings. All nodes were examined using haematoxylin-eosin staining. RESULTS: Preoperative LS was successful in all patients. Preferential pathways of lymphatic drainage were identified: level II of the neck was the most common lymphatic drainage pattern, followed by levels IV and III. Contralateral drainage occurred in 11 patients and in two of them metastatic nodes were found on the contralateral side. Metastases were observed only in radioactive lymph nodes. CONCLUSION: LS is able to supply a complete map of the lymphatic drainage before surgery, making it possible to tailor selective neck dissection to each individual patient based on the results of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing surgery-related morbidity.

Adult↗

Sentinel lymph node biopsy in multicentric breast cancer. The experience of the European Institute of Oncology.

AIM: To present our experience with sentinel lymph node biopsy (SLNB) performed in patients with multicentric breast cancer. METHODS: Between May 2001 and May 2004, 42 patients with multicentric breast cancer and a clinically negative axilla underwent lymphatic mapping either by a single subareolar (n = 25) or a double peritumoral/subdermal injection (n = 17) of 99Tc-HSA nanocolloids. The sentinel lymph node (SLN) was evaluated by intraoperative frozen section and axillary dissection was performed only in case of positive SLN. RESULTS: Mean age was 49 years (range 25-78). Mean number of SLNs identified by lymphoscintigraphy was 1.36 (range 1-5) and mean number of SLNs removed at surgery was 1.55 (range 1-5), with an identification rate of 100%. The mean number of hot spots identified by lymphoscintigraphy was similar in patients who underwent single or double injections (1.36 and 1.35, respectively). In 21 of 42 patients the SLN was positive, and in seven of these 21 patients the SLN was the only positive node. After a median follow-up of 24 months no overt axillary metastases occurred in patients with negative SLN. CONCLUSIONS: The number of SLNs is not dependent on the number and site of injections. SLNB is our standard procedure for nodal staging in patients with multicentric breast cancer and a clinically negative axilla.

Adult↗

Carcinoid crisis induced by receptor radionuclide therapy with 90Y-DOTATOC in a case of liver metastases from bronchial neuroendocrine tumor (atypical carcinoid).

SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.

Aged↗

Vascular tumor targeting.

The growth of solid tumors is dependent on their capacity to acquire blood supply. Therefore, much effort has been directed towards the development of anti-angiogenic agents which inhibit the process of neovascularization. More recently, it has become apparent that the targeted destruction of the established tumor vasculature represents a complementary avenue for growing therapeutic opportunities. This review provides evidence that vascular tumor targeting is an effective anti-tumor strategy in animal models. It further describes strategies for the identification of putative tumor vascular targets and discusses future prospects for vascular targeting applications in the clinical setting.

Drug Delivery Systems↗

Sentinel lymph node biopsy for localised ductal carcinoma in situ?

Intraductal carcinoma of the breast (DCIS), by definition, cannot give axillary metastases. Axillary dissection is therefore not indicated. The role of the sentinel lymph node (SLN) biopsy in the management of DCIS has not yet been established. A 6-13% risk of SLN involvement is reported in Literature. The aim of the present study is to assess the role of SLN biopsy in patients with pure DCIS and attempt to identify guidelines for routine practice in managing such patients. From March 1996 to December 2003, 508 consecutive patients with pure DCIS of the breast underwent SLN biopsy at the European Institute of Oncology in Milan. Clinical and pathological data were prospectively collected. In all cases of previous surgery or stereotactic biopsy performed elsewhere all pathological slides were reviewed. Cases with microinvasion were excluded from this investigation. Lymphatic mapping was performed using a radiocolloid technique. Most of the patients underwent conservative surgery and removal of the SLN which was sent for conclusive histology. SLN metastases were detected in 9 out of 508 (1.8%) patients. In five patients only micrometastasis (<2 mm) was detected. Eight patients underwent complete axillary dissection. In none of these patients did we find additional positive axillary lymph nodes. In conclusion, due to the low prevalence of metastatic involvement (1.8%), SLNB should not be considered a standard procedure in the treatment of all patients with DCIS. In pure non-comedo DCIS completely excised by radical surgery with free margins of resection SLNB should be avoided since not only it is unnecessary but could also jeopardize a successive re-SLNB in case of invasive recurrence. A very extensive and accurate histological examination of the tumour in DCIS is compulsory to exclude micro-invasive foci and, finally, to decrease the prevalence of unexpected SLN metastases. SLNB should be considered in case of DCIS where there exists a strong doubt of invasion at the definitive histology, such as large solid tumours or diffuse or pluricentric microcalcifications undergoing mastectomy. Moreover, if the trend is statistically confirmed with a wider population, large comedo-DCIS, presenting superior risk of SLNs metastasis, could be scheduled for SLNB. If the SLN is micrometastatic complete axillary dissection is not unavoidable.

Breast Neoplasms↗

Development of axillary surgery in breast cancer.

Axillary surgery is a critical part of the treatment of breast carcinoma: its importance is related to the staging of disease, prescription of adjuvant therapy and prognosis. For years, complete axillary dissection has remained the standard approach to breast cancer lymphatic staging; its value is still high, but the development of sentinel-node biopsy has significantly changed the indication of the procedure. We discuss the evolution of axillary surgery in breast cancer.

Axilla↗

Safety of sentinel node biopsy in pregnant patients with breast cancer.

BACKGROUND: Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) have typically been contraindicated for pregnant patients diagnosed with breast cancer because they are considered unsafe. PATIENTS AND METHODS: Twenty-six premenopausal non-pregnant patients who were candidates for LS underwent peritumoral injection of approximately 12 MBq of 99mTc-HSA nanocolloids. Static [15 min and 16 h post-injection (p.i.)] and whole-body (16 h p.i.) scintigraphic images were acquired. Activity concentration in the urine (0-2, 2-4, 4-8, 8-16 h p.i.) was evaluated by a gamma-counter. Activity in the bloodstream was measured at 4 and 16 h p.i. Thermoluminescent dosimeters (TLD) were placed, before tracer injection, on the injection site, between injection site and epigastrium (two points), and on the epigastrium, umbilicus and hypogastrium, and were removed before surgery. RESULTS: Scintigraphic images showed no radiotracer concentration except in the injection site and in the sentinel node. In all patients, the total activity excreted within the first 16 h was <2% of the injected activity. Activity in the blood pool was, at each time point, <1% of the injected activity. In 23 of 26 patients, all absorbed dose measurements were lower than the sensitivity of the TLD (<10 microGy); in the remaining three patients, the absorbed doses at the level of epigastrium, umbilicus and hypogastrium were in the following ranges: 40-320, 120-250 and 30-140 microGy, respectively. CONCLUSIONS: According to our standard technique (12 MBq of 99mTc-HAS), LS and SLNB can be performed safely during pregnancy, since the very low prenatal doses from this diagnostic procedure, when properly performed, do not significantly increase the risk of prenatal death, malformation or mental impairment.

Adult↗

Thyroid disease in northern Italian children born around the time of the Chernobyl nuclear accident.

BACKGROUND: The Chernobyl nuclear accident of 1986 caused a dramatic increase in the incidence of thyroid cancers in exposed children in Belarus. Airborne radioactivity from the reactor spread over northern Italy, where rainout gave rise to low levels of radioactivity at ground level. PATIENTS AND METHODS: As the latency between exposure to ionising radiation and development of thyroid cancer is thought to be about 10 years, in 1996/1997 all children born in 1985 and 1986 and attending school in an area of Milan, Italy were examined for thyroid nodules. A total of 3949 children were examined by two physicians blinded to the examination and diagnosis of the other. The children were to be reassessed in 2001/2002. RESULTS: In total, 1% had palpable nodules. The nodule diagnoses were: Hurtle cell adenoma (one), thyroglossal duct cyst (one), thyroid cyst (four) and thyroiditis (four). The prevalence of thyroid disease in the cohort was indistinguishable from that of populations not exposed to radioactive pollution. Only 10 children re-presented for examination 5 years later; all were negative. The direct costs of the study were estimated at 21,200 Euros. CONCLUSION: The high cost of the study in relation to reassuring lack of increase in thyroid nodule prevalence suggests that further studies are not justified.

Chernobyl Nuclear Accident↗

The use of standardized uptake values for assessing FDG uptake with PET in oncology: a clinical perspective.

Among clinicians who use positron emission tomography (PET), the standardized uptake value (SUV) is a popular semi-quantitative value that can be easily assessed whenever a PET study is performed under physiological and pathological conditions. It provides an index of regional tracer uptake normalized to the administered dose of tracer. The simplicity of SUV assessment contrasts with the complexity of full quantitative procedures requiring blood sampling and possibly dynamic scanning, which limits patient throughput and significantly increases the workload of a PET centre. Two main clinical conditions/variables affect the significance and usefulness of the SUV: the type and stage of the disease being assessed. Diagnosis, prognosis and therapy monitoring represent the possible uses of SUV. In the above clinical conditions an SUV may provide information about the single lesion in which it is assessed, but the utility of such information depends largely on its integration with all the available clinical and instrumental data.

Algorithms↗

Combined treatment of glioblastoma patients with locoregional pre-targeted 90Y-biotin radioimmunotherapy and temozolomide.

AIM: In a previous phase I-II study, the safety profile and anti-tumor efficacy of pre-targeting locoregional radioimmunotherapy (LR-RIT), based on the ''3 step'' method, was assessed in 24 high-grade glioma patients. The encouraging results in terms of low toxicity and objective response rate (25%) prompted us to continue our study. METHODS: An analysis of 73 patients with hystologically confirmed glioblastoma multiforme (GBM), treated with the ''3 step'' (90)Y-biotin based LR-RIT, is herein reported. All patients had a catheter implanted at 2(nd) surgery and underwent at least 2 cycles of LR-RIT (range 2-7) with 2 months interval. Thirty-five out of 73 patients were also treated with Temozolomide (TMZ). Two cycles of TMZ (200 mg/m(2)/day, for 5/28 days) were administered in between each course of LR-RIT. Overall survival (OS) and progression free survival (PFS) were retrospectively calculated. RESULTS: Stabilization of disease was achieved in 75% of patients, while 25% progressed. In the 38 patients treated with LR-RIT alone, median OS and PFS were respectively 17.5 months (95%CI=[17-20]) and 5 months (95%CI=[4-8]), while in the 35 treated with the combined treatment (LR-RIT+TMZ) respective values were 25 months (95%CI=[23-30]) and 10 months (95%CI=[9-18] (p<0.01). The addition of TMZ to LR-RIT did not increase neurological toxicity, and no major hematological toxicity was observed. CONCLUSION: These results confirm the safety and the efficacy of (90)Y LR-RIT in recurrent GBM patients; the addition of TMZ significantly improved the overall outcomes; a further controlled prospective, randomized study is fully justified.

Antineoplastic Agents, Alkylating↗

Optimised nuclear medicine method for tumour marking and sentinel node detection in occult primary breast lesions.

The aim of this study was to evaluate the feasibility of sentinel node (SN) biopsy in occult breast lesions with different radiopharmaceuticals and to establish the optimal lymphoscintigraphic method to detect both occult lesions and SNs (SNOLL: sentinel node and occult lesion localisation). Two hundred and twenty-seven consecutive patients suspected to have clinically occult breast carcinoma were enrolled in the study. In addition to the radioguided occult lesion localisation (ROLL) procedure, using macroaggregates of technetium-99m labelled human serum albumin (MAA) injected directly into the lesion, lymphoscintigraphy was performed with nanocolloids (NC) injected in a peritumoral (group I) or a subdermal site (group II). In group III, a sole injection of NC was done into the lesion in order to perform both ROLL and SNOLL. Overall, axillary SNs were identified in 205 of the 227 patients (90.3%). In 12/62 (19.4%) patients of group I and 9/79 (11.4%) patients of group III, radioactive nodes were not visualised, whereas SNs were successfully localised in 85 of 86 patients of group II ( P<0.001). Pathological findings revealed breast carcinoma in 148/227 patients (65.2%) and benign lesions in 79 (34.8%). A total of 131 axillary SNs were removed in 118 patients with breast carcinoma; intraoperative examination of the SNs revealed metastatic involvement in 16 out of 96 cases of invasive carcinoma (16.7%). It is concluded that the combination of the ROLL procedure with direct injection of MAA into the lesion and lymphoscintigraphy performed with subdermal injection of radiocolloids represents the method of choice for accurate localisation of both non-palpable lesions and SNs.

Adult↗

Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue.

Oxytocin receptors (OTR) have been described in a number of tumours of different origin, and represent a new target for specific radiolabelled oxytocin (OT) analogues in cancer diagnosis and therapy. By linking the DOTA chelating agent to position 8 of the deamino derivative of Lys(8)-vasotocin (dLVT), we obtained a new compound (DOTA-dLVT) with the following characteristics: (1) it forms a monomeric and stable compound that binds to OTR with an affinity comparable to that of the endogenous OT ligand; (2) it is characterised by a very good selectivity profile for the human OTR, with a low affinity binding to the closely related V1a, V1b and V2 vasopressin receptor subtypes; (3) it induces rapid and persistent receptor internalisation and (4) when radiolabelled, [(111)In]-DOTA-dLVT is efficiently and selectively taken up by OTR-positive tumours grown in mice. These features makes radiolabelled DOTA-dLVT a very good candidate for the radiotargeting of OTR-expressing tumours.

Animals↗