Radioguided occult lesion localization of cervical recurrences from differentiated thyroid cancer: technical feasibility and clinical results.

AIM: We explored the feasibility of radioguided occult lesion localization (ROLL) for radioiodine-negative cervical recurrences from differentiated thyroid cancer (DTC). METHODS: The procedure was performed in 32 patients (3 patients being operated twice); 15/32 patients had had multiple prior lymph node dissections ("hostile" anatomy). 99mTc-albumin macro-aggregates (99mTc-MAA) were injected intra-lesionally under ultrasound guidance; 2 to 18 hours later, a hand-held gamma-probe helped to localize the lesions intraoperatively and to ascertain removal of the radiolabeled lesions. Mini-invasive excision of the radiolabelled lesions was performed in 12 cases (m-ROLL), while a modified radical neck dissection was performed in 23 cases after radioguided lymphadenectomy (d-ROLL). Fifty-nine lesions were radiolabelled (mean size 11±4.5 mm). RESULTS: Radioguidance allowed to identify/remove 56/59 lesions (95%). Some leakage of 99mTc-MAA in the surrounding tissues hampered detection of 3 lesions, which were removed anyway (100% overall localization). Histopathology confirmed metastatic involvement of the radiolabeled lesions and some additional metastases in other nodes. Neither nerve injury nor hypoparathyroidism occurred. After a median follow-up of 29 months, 19 patients were disease-free, 12 patients developed loco-regional recurrences, 1 patient had distant metastases and 1 patient had both loco-regional and distant metastases. Recurrences rates were 33% for m-ROLL and 40% for d-ROLL. CONCLUSIONS: The ROLL technique is feasible in selected patients with loco-regional recurrence from DTC, proving to be particularly useful also in patients already submitted to cervical dissections and/or with small lesions located in surgically difficult sites. It can therefore have a clinical role in the management of cervical DTC recurrences.

Radionuclide therapy and integrated protocols for bone metastases.

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.

Comparative performance of two inhaler systems to assess distribution of convective ventilation by 99mTc-labeled aerosol scintigraphy in patients with airway obstruction.

AIM: Redistribution of convective ventilation, the leading disorder in airway obstruction, is a target of pharmacological and mechanical ventilation treatments for patients with chronic obstructive pulmonary disease (COPD). Convective ventilation is visualized by ventilation scintigraphy using radiolabeled aerosol particles that should ideally deposit in the terminal airspaces, but not in the conducting airways, and have no Brownian motion (which characterizes diffusive ventilation). Currently available commercial systems do not meet these requirements as they do not ensure an optimal size of aerosol droplets delivered at the mouthpiece. METHODS: A new inhaling system (FAI) was developed and designed so as to yield radioaerosol droplets with smaller particle size and to ensure more efficient aerosol delivery to the terminal airways than that obtained with a widely available commercial system (MMI). A cascade impactor was employed to measure the size of the radioactive droplets at the mouthpiece. Preliminary comparative validation was based on ventilation scintigraphy using the two systems (both followed by a standard lung perfusion scan) in control subjects and in patients with airway obstruction. The time required to reach a certain count rate in the lung fields (1 kc/s) was recorded by means of dynamic g camera acquisition during breathing. Subsequent static images allowed assessment of intrapulmonary distribution of ventilation (by both visual and quantitative evaluation) and of the ventilation/perfusion (V/Q) ratios relative to the upper, middle, and lower thirds of the lung fields. RESULTS. FAI yielded 99mTc-labeled droplets with a count median diameter of 1.4 microm and a geometric standard deviation of 2 microm , versus 3 microm and 2, respectively, produced by the commercial inhaler (MMI). The mean time to reach the 1 kc/s count rate was significantly shorter with the FAI than with the MMI both in control subjects (4.7+/-1.7 min versus 8.2+/-2 min, P<0.04) and in airway-obstructed patients (3.4+/-0.8 min versus 8.4+/-2 min, P<0.001). With the MMI, appreciable radioaerosol deposition in the large bronchi prevented reliable quantitative assessment of ventilation, even in the control subjects. With the FAI, radioaerosol deposition in the central large airways was never observed in the controls and was only sporadically or occasionally observed in patients with COPD or asthma, respectively. This feature allowed quantitative ventilation assessment. The FAI-generated radioaerosol particles reached the peripheral respiratory spaces more efficiently than those generated by MMI; on the ventilation scans, the FAI allowed better discrimination than the MMI of the different pathophysiologic conditions. CONCLUSION: These findings consistently indicate that the smaller-sized radiolabeled droplets generated by FAI, combined with the better breathing dynamics of the inhaler device, result in better overall performance as compared to the commercial system. This makes scintigraphic images obtained with the new device especially suitable for assessing convective ventilation in COPD patients, a particularly helpful feature for analytically describing the distribution patterns observed in airway-obstructed patients and for evaluating the effects of drugs, mechanical ventilation, and other interventions in such patients.