Ultrasound screening for thyroid nodules and cancer in individuals with family history of thyroid cancer: a micro-costing approach.

PURPOSE: Screening programs that target healthy populations are an important tool for identifying unrecognized, asymptomatic disease. However, ultrasound screening for thyroid cancer has no obvious advantage in terms of cost-effectiveness in asymptomatic adults. There is far less consensus (and data) on the indications for screening in high-risk individuals. The aim of the study was to estimate the costs of ultrasound screening for individuals with first-degree family history of thyroid cancer. METHODS: We conducted a prospective cross-sectional study from January 1, 2009 through December 31, 2018 in the Thyroid Cancer Outpatient Clinic of a large teaching hospital in Rome, Italy. We estimated the costs of an ultrasound screening protocol using the micro-costing bottom-up method. RESULTS: For individuals without thyroid nodules, the screening examination had an estimated cost of €66.21 per screenee. For those found to have unsuspicious nodules, the estimated cost rose to €119.52 per screenee, owing to the addition of thyroid function tests. The estimated cost of screening for a subject with newly diagnosed nodules that were submitted to cytology was €259.89. The total cost of screening for the entire population of 1176 individuals was € 118,133.85. The total expenditure to confirm a single thyroid cancer diagnosis was €10,598.71. CONCLUSION: A sonographic screening implies a significant direct expenditure and is likely to detect a very large number of individuals with benign nodules (more than 45 asymptomatic individuals are diagnosed with a thyroid nodule for each newly detected cancer case), whose long-term follow-up will further increase healthcare costs.

Lack of association between obesity and aggressiveness of differentiated thyroid cancer.

PURPOSE: Aim of this study was to evaluate the association between body mass index (BMI) and aggressive features of differentiated thyroid cancer (DTC) in a prospective cohort. METHODS: Patients with DTC were prospectively enrolled at a tertiary referral center and grouped according to their BMI. Aggressive clinic-pathological features were analyzed following the American Thyroid Association Initial Risk Stratification System score. RESULTS: The cohort was composed of 432 patients: 5 (1.2%) were underweight, 187 (43.3%) normal weight, 154 (35.6%) overweight, 68 (15.7%) grade 1 obese, 11 (2.5%) grade 2 obese and 7 (1.6%) grade 3 obese. No single feature of advanced thyroid cancer was more frequent in obese patients than in others. No significant correlation was found between BMI, primary tumor size (Spearman's ρ - 0.02; p = 0.71) and ATA Initial Risk Stratification System score (ρ 0.03; p = 0.49), after adjustment for age. According to the multivariate logistic regression analysis, male gender and pre-surgical diagnosis of cancer were significant predictors of cancer with high or intermediate-high recurrence risk according to the ATA system (OR 2.06 and 2.51, respectively), while older age at diagnosis was a protective factor (OR 0.98), and BMI was not a predictor. BMI was a predictor of microscopic extrathyroidal extension only (OR 1.06). CONCLUSIONS: Obesity was not associated with aggressive features in this prospective, European cohort of patients with DTC.

131I therapy and Graves' disease in a long term observation: euthyroidism is a suitable goal. Our experience.

OBJECTIVE: The aim of the study was to verify early and definitive outcome of radioiodine therapy in patients with Graves' disease, administering 131I calculated dose to pursue euthyroidism. PATIENTS AND METHODS: We retrospectively analyzed 639 patients affected by Graves' disease and treated by one or more 131I calculated doses. Results dose by dose are reported. As to the first administration, outcome is related to parameters used to calculate dose and to patients' available features. Failures and hypothyroidism onset are evaluated. RESULTS: A mean dose of 10 mCi shows great effectiveness: 75% of patients were cured after one administration, 88% after two. Of the failures, 84.1% occurred in a mean time of 0.34±0.23 years and were more frequent for larger glands, accelerated intra-gland radioiodine turnover, ophtalmopathy, administration of antithyroid drugs until 131I therapy. Of hypothyroid patients, 39.8% were diagnosed within the first year. After a sharp initial rise, hypothyroidism occurred at a slower rate, with estimated yearly increases of 3.8% until 10 years and of 1.8% later. In still followed up patients, euthyroidism was observed in about half the population after 10 years and in a third after 25 years. CONCLUSIONS: 131I can be the first line treatment for Graves' disease in small-medium thyroids. Calculated doses can achieve a high amount of long term euthyroid patients. Similar results could be expected by fixed doses of 10 mCi.

Lymph node metastases from differentiated thyroid carcinoma: does radioiodine still play a role?

OBJECTIVES: Ultrasonography and surgery have now become the elective diagnostic and therapeutic tools for neck lymph node (LN) metastases from differentiated thyroid carcinoma (DTC), reserving radioiodine therapy (RAI) for surgery failures. Aim of the present retrospective study was to evaluate results of RAI in cases of LN metastases displaying (131)I uptake over a long-term observation period and its possible role today. MATERIALS AND METHODS: From a series of 1276 patients who had undergone surgery for DTC, 130 cases were selected showing (131)I uptaking LN metastases, detected during follow-up scans and who were then submitted to surgery and/or RAI. Patients were divided into groups according both to extent of surgery, with/without lymphectomy, and to following treatment and outcome. RESULTS: The initial surgical approach does not seem to significantly influence the outcome. (131)I therapy alone, sometimes at low doses, can be very effective in the management of LN metastases detected at Whole Body Scan, but multiple doses are often needed. The age at diagnosis is confirmed as a negative prognostic factor. CONCLUSIONS: Considered radioprotection questions, RAI may solve (131)I uptaking LN metastases, above all if < 10 mm. For larger LN metastases and in the case of failure of RAI surgical excision is mandatory, while a subsequent therapeutic dose of (131)I could be useful to reveal incomplete excision.

Our experience on pain palliation of bone metastasis with Sr-89 or Sm-153 in cancer patients resistant to a conventional analgesic therapy. A retrospective study.

OBJECTIVES: These retrospective study is aimed to evaluate the efficacy of therapy with Stronthium-chloride 89 (89SrCl) and Samarium 153 conjugated with ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) in the palliation of bone pain due to metastatic malignancy. MATERIALS AND METHODS: The study refers to a presentation sample of 27 patients with bone metastases caused by different cancers (16 prostate, 5 breast, 6 lung) who were enrolled and followed-up for 11.5 +/- 6.3 months. 89SrCl (150MBq) was administered in 17 pts, 153Sm-EDTMP (37 MBq/Kg) in 10 pts. All patients showed multiple metastatic sites of 99Tc-HDP uptake documented by a standard bone scintigraphy. Effectiveness of treatment was evaluated by questionnaires about pain and quality of life, Karnofsky index, specific cancer markers, a post-treatment bone scintigraphy. Presence of flare reaction and haematological toxicity were evaluated too. RESULTS: Questionnaire scores decreased both in patients treated with 89SrCl and in those given 153Sm-EDTM, without significant difference. Karnofsky index significantly increased only in patients with prostate cancer. After therapy, there were no significant changes of tumor marker levels, neither in bone scintigraphic pattern. Flare reaction occurred in 44% of the cases within 2 weeks from the therapy. Remarkable variations of platelets and leukocytes occurred in 33.3% and 18.5% of patients, respectively, independently of the radiopharmaceutical used, but reversed within 6 weeks after therapy. CONCLUSIONS: Radionuclide therapy with bone-seeker agents 89Sr and 153Sm in the palliation of painful bone metastases allows a partial/total relief of pain with an improvement of quality of life. No tumoricid effect was found. Haematological toxicity was limited and reversible. Patients with prostate cancer seem to have a higher response rate.

Thyroid stunning in clinical practice: is it a real problem?

Stunning is a phenomenon of reducing (131)I uptaking activity by residual or metastatic tissue during the follow-up of patients after total thyroidectomy for differentiated thyroid carcinoma. It was observed at whole body scintigraphy performed after therapeutic dose, administered for remnant ablation, in patients who were previously given a (131)I dose for diagnostic purpose. This phenomenon could influence the efficacy of radioisotopic therapy, making it unsuccessful. Stunning was observed also in case of hyperthyroidism treated by fractionated doses of (131)I. After a careful revision of literature, Authors report their last 10 years-experience about very few cases of supposed stunning, observed in oncological and hyperthyroidal patients who underwent diagnostic scan and radioiodine therapy. In case of differentiated thyroid carcinoma, we recommended a careful selection of patients who will be given ablative therapy using very low diagnostic doses and administering further therapeutic dose in a short time. In case of hyperthyroidism treatment, it is confirmed the opportunity of a single therapeutic dose with TSH value within the normal range. Because it was found out a very small number of cases in our wide population, we conclude that stunning is not influent in clinical practice, above all if ''well-practice'' diagnostic-therapeutical procedures are strictly observed.

A finding of myocardial uptake at a bone scintigraphy with Tc-99m HDP.

We present a patient admitted to our Department for a Tc-99m HDP three-phase bone scintigraphy to evaluate a hip prosthesis. Delayed images showed diffuse myocardial uptake at whole body scan. In such cases, several diseases should be considered in the differential diagnosis.

Sensitivity of [99mTc]methoxyisobutylisonitrile scan in patients with metastatic differentiated thyroid cancer.

AIM: The aim of the present study was to evaluate the diagnostic sensitivity of [(99m)Tc]methoxyisobutylisonitrile ([(99m)Tc]MIBI) in a large series of patients with metastatic differentiated thyroid carcinoma (DTC), as compared with (131)I-whole body scan (WBS) and other diagnostic imaging techniques. METHODS: Eighty-four patients with known metastases from DTC where recruited during the course of replacement thyroxine therapy and undergone [(99m)Tc]MIBI scan. All patients previously performed a (131)I-WBS with thyroglobulin (Tg) measurement and neck ultrasound or computerized tomography, or magnetic resonance imaging, or bone scan or positron emission tomography (PET) scan. RESULTS: Patients were divided in two groups: group A (n=50) with known metastases and positive at a previous (131)I-WBS and group B (n=34) with known metastases, but negative at (131)I-WBS. All patients had elevated serum Tg level in absence of replacement therapy. Technetium-99m-MIBI scan showed 76.2% sensitivity in detecting metastases, Tg during opotherapy 64.3%, and the other imaging techniques combined 86.9%. Sensitivity of [(99m)Tc]MIBI was greater in metastases without (131)I uptake than in metastases with (131)I uptake, although the difference was not statistically significant. CONCLUSION: Technetium-99m-MIBI scan improves sensitivity of Tg measurement in patients with suspected metastases from DTC during the course of opotherapy and is a useful alternative to fluorodeoxyglucose-PET or other imaging techniques in patients with elevated serum Tg and negative (131)I-WBS.

Lung metastases from differentiated thyroid carcinoma. A 40 years' experience.

AIM: Retrospective studies have been carried out to estimate the survival of 96 patients with lung metastases from differentiated thyroid carcinoma, observed from 1958 to 2000. METHODS: All patients had undergone total thyroidectomy. Case histories were analysed with respect to age at diagnosis, sex, histology, local lymph node involvement, size of lung metastases and 131I uptake by metastases. Survival functions were calculated. Cox regression was performed. RESULTS: There was no statistically significant difference in histological type and lymph node involvement, whereas a significantly longer survival time was observed in patients under 45 years of age at diagnosis (p= or <0.0001), in those with metastases concentrating 131I (p= or <0.0001) and in those with fine miliaric metastases (p=0.0037). Multi-variate analysis revealed that the risk of death increases about 5.4-fold in patients over 45 years old, whereas 131I treatment is likely to reduce this risk to nearly 1/6. Conclusion. In conclusion, in patients with lung metastases from differentiated thyroid carcinoma, young age at diagnosis and 131I uptake by metastases are the most important factors positively affecting survival time. Radioiodine therapy, also with high cumulative 131I activity, can lead to longer survival time or complete recovery.

Micronucleus yield and colorimetric test as indicators of damage in patients' lymphocytes after 131I therapy.

UNLABELLED: To estimate the absorbed dose received by patients who underwent 131I therapy, a modified compartmental model of the International Commission on Radiological Protection (ICRP) was used. The activity in plasma and micronucleus (MN) frequency (MN test) were measured before and after therapy. To evaluate whether a correlation exists between lymphocytes and absorbed dose, a colorimetric test, based on the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT test), was used. METHODS: Twenty patients who underwent 131I therapy were studied. Activity was measured in plasma, and isolated lymphocytes were collected to perform the MN and MTT tests. RESULTS: The mean MN frequency observed in unexposed patient lymphocytes was comparable with that of healthy subjects. 131I therapy induces a small increase in MN, and a good correlation with the bone marrow absorbed dose was obtained (P = 0.040). A consistent decrease in phytostimulation observed after therapy (MTT test) correlated significantly with bone marrow absorbed dose (P = 0.0085). CONCLUSION: The MTT test appears to be more reliable than the MN test for evaluating lymphocyte damage induced by 131I therapy.

Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: role of magnetic resonance imaging.

Nineteen patients (16 men and 3 women, mean age 51 years) with previous anterior myocardial infarction and severe stenosis (> or = 90%) of the left anterior descending coronary artery were studied by magnetic resonance imaging (MRI) without and with contrast media to verify the capability of MRI in identifying viable myocardium in areas of severe systolic dysfunction. In corresponding left ventricular segments, a comparison was made between regional signal intensities (SI) determined on MRI images before and 4, 8, 12, and 30 minutes after administration of paramagnetic contrast media (gadolinium diethylenetriaminepentaacetic acid, 0.4 mmol/kg intravenously) and metabolic parameters determined by iodine 123 phenylpentadecanoic acid (IPPA) scintigraphy. The SI and the time of maximum postcontrast enhancement were analyzed by dividing the left ventricle into 11 segments. Each segment was classified as normal (group 1, n = 116), hibernating (group 2, n = 50), or necrotic (group 3, n = 43) on the basis of the IPPA washout rate (> 30%, 10% to 30%, and < 10%, respectively). Regional SI demonstrated significant differences in absolute values at 12 minutes (group 3: 1.62 +/- 0.58 vs group 1: 1.32 +/- 0.52, p < 0.01, and vs group 2: 1.34 +/- 0.48, p < 0.05) and at 30 minutes (group 3: 1.71 +/- 0.47 vs group 1: 1.21 +/- 0.55, p < 0.01, and vs group 2: 1.49 +/- 0.57, p < 0.05) and in temporal distribution. These results suggest that MRI has a potential role in differentiating viable from necrotic myocardium in patients with chronic severe systolic dysfunction.

Characterization of reversible myocardial dysfunction by magnetic resonance imaging.

Some recent cardiovascular applications of nuclear magnetic resonance imaging (MRI) are discussed, on the basis of both literature and personal data. Management of coronary patients has become directed to strategies aiming at salvaging the ischemic myocardium, and MRI can play an important role in providing the necessary data leading to an appropriate assessment. Due to its capability in showing morphofunctional information on wall thickness and thickening, cine-MRI technique can be used to detect myocardial ischemia and infarction, since it allows the acquisition of 16 or more frames of the cardiac cycle which can be displayed in a cine loop format. In an Italian Cooperative Study the role of MRI in discriminating stunned from necrotic areas has been investigated. Comparison of fractional area change by echo versus cine-MR turned out to be almost completely overlapping, but cine-MRI allowed a more accurate measurement of systolic wall thickening due to better visualization of endo- and epicardial borders (more sensitive marker of kinetic damage than wall motion). Other studies have also been performed in order to determine the capability of contrast agents of allowing differentiation between reperfused reversible and irreversible myocardial injury and allowing distinction between reperfused and occlusive myocardial infarction. In a recent study we investigated the MRI possibility of identifying viable myocardium in severely chronic systolic dysfunctioning areas by comparing, in corresponding left ventricular segments, regional perfusion and metabolism at IPPA scintigraphy and regional signal intensity at MR images obtained before and after paramagnetic contrast media administration. The potential role of MRI was shown in the identification of viable myocardium with the use of contrast medium, that is of crucial importance in this respect.

[Role of the endogenous opioid system in the modulation of anginal pain]. / Ruolo del sistema oppioide endogeno nella modulazione del dolore anginoso.

The Authors make an analysis of the complex interactions occurring between peripheral and central factors in the regulation of anginal pain. As for the role of the endogenous opioid system, results obtained in a study using a particular methodological approach have demonstrated that patients with asymptomatic ischemic heart disease have a higher endogenous opioid tone at the level of the central nervous system.