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This observational study aims to evaluate the efficacy of naloxegol therapy in resolving opioid-induced constipation (OIC) and in improving the quality of life in a home palliative care cancer setting. Advanced cancer patients with OIC (Rome IV criteria) not relieved by laxatives started a naloxegol therapy 25 mg/day for 4 weeks. Quality of life was evaluated by Patient Assessment of Constipation Quality-of-Life (PAC-QoL) at day 0 and day 28; background pain by Numerical Rating Scale, number of weekly spontaneous bowel movements and Bowel Function Index (BFI) were evaluated at day 0 and every week. Seventy-eight patients who completed the 4-week study improved all four PAC-QoL dimensions (physical and psychological discomfort, worries/concerns and satisfaction level). Weekly spontaneous bowel movements increased and BFI improved. Background pain reduced after seven days and remained lower during the following weeks. Seventy-two patients dropped out the study before day 28 with a reduced survival compared to patients completing the study. Even in these patients, an improvement of bowel function was observed after two weeks. Naloxegol was effective in improving the quality of life, resolving OIC and reducing overall pain in patients with advanced cancer.

The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells' inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy., Competing Interests: The authors declare no conflict of interest.

The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.

Objective: Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment., Methods: A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 4 >2 μUI/mL., Results: This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups., Conclusion: TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment., Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography.

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.

Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg ≥1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels ≤1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (<10 ng/mL). In unselected PTC cohorts with incomplete/indeterminate biochemical responses to thyroidectomy and RRA, periodic remeasurement of stimulated Tg allows most patients to be classified as disease-free.

Studies from single institutions have analyzed BRAF in papillary microcarcinomas, sometimes with contradictory results. Most of them have provided limited integration of histological and clinical data. To obtain a comprehensive picture of BRAF V600E-mutated microcarcinomas and to evaluate the role of BRAF testing in risk stratification we performed a retrospective multicenter analysis integrating microscopical, pathological, and clinical information. Three hundred and sixty-five samples from 300 patients treated at six medical institutions covering different geographical regions of Italy were analyzed with central review of all cases. BRAF V600E statistical analysis was conducted on 298 microcarcinomas from 264 patients after exclusion of those that did not meet the required criteria. BRAF V600E was identified in 145/298 tumors (49%) including the following subtypes: 35/37 (95%, P<0.0001) tall cell and 72/114 (64%, P<0.0001) classic; conversely 94/129 follicular variant papillary microcarcinomas (73%, P<0.0001) were BRAF wild type. BRAF V600E-mutated microcarcinomas were characterized by markedly infiltrative contours (P<0.0001) with elongated strings of neoplastic cells departing from the tumor, and by intraglandular tumor spread (P<0.0001), typically within 5 mm of the tumor border. Multivariate analysis correlated BRAF V600E with specific microscopic features (nuclear grooves, optically clear nuclei, tall cells within the tumor, and tumor fibrosis), aggressive growth pattern (infiltrative tumor border, extension into extrathyroidal tissues, and intraglandular tumor spread), higher American Thyroid Association recurrence risk group, and non-incidental tumor discovery. The following showed the strongest link to BRAF V600E: tall cell subtype, many neoplastic cells with nuclear grooves or with optically clear nuclei, infiltrative growth, intraglandular tumor spread, and a tumor discovery that was non-incidental. BRAF V600E-mutated microcarcinomas represent a distinct biological subtype. The mutation is associated with conventional clinico-pathological features considered to be adverse prognostic factors for papillary microcarcinoma, for which it could be regarded as a surrogate marker. BRAF analysis may be useful to identify tumors (BRAF wild type) that have negligible clinical risk.

Objective: The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis is widely recognized, but less is known about the possible link between circulating anti-thyroglobulin antibody (TgAb) titers and PTC aggressiveness. To shed light on this issue, we retrospectively examined a large series of PTC patients with and without positive TgAb., Methods: Data on 220 TgAb-positive PTC patients (study cohort) were retrospectively collected in 10 hospital-based referral centers. All the patients had undergone near-total thyroidectomy with or without radioiodine remnant ablation. Tumor characteristics and long-term outcomes (follow-up range: 2.5-24.8 years) were compared with those recently reported in 1020 TgAb-negative PTC patients with similar demographic characteristics. We also assessed the impact on clinical outcome of early titer disappearance in the TgAb-positive group., Results: At baseline, the study cohort (mean age 45.9 years, range 12.5-84.1 years; 85% female) had a significantly higher prevalence of high-risk patients (6.9% vs. 3.2%, p<0.05) and extrathyroidal tumor extension (28.2% vs. 24%; p<0.0001) than TgAb-negative controls. Study cohort patients were also more likely than controls to have persistent disease at the 1-year visit (13.6% vs. 7.0%, p=0.001) or recurrence during subsequent follow-up (5.8% vs. 1.4%, p=0.0001). At the final follow-up visit, the percentage of patients with either persistent or recurrent disease in the two cohorts was significantly different (6.4% of TgAb-positive patients vs. 1.7% in the TgAb-negative group, p<0.0001). At the 1-year visit, titer normalization was observed in 85 of the 220 TgAb-positive individuals. These patients had a significantly lower rate of persistent disease than those who were still TgAb positive (8.2% vs. 17.3%. p=0.05), and no relapses were observed among patients with no evidence of disease during subsequent follow-up., Conclusions: PTC patients with positive serum TgAb titer during the first year after primary treatment were more likely to have persistent/recurrent disease than those who were consistently TgAb-negative. Negative titers at 1 year may be associated with more favorable outcomes.

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.

Purpose of the Report: Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures., Patients and Methods: Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered., Results: A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months., Conclusions: 131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.

Context: The current use of life-long follow-up in patients with papillary thyroid cancer (PTC) is based largely on the study of individuals diagnosed and treated in the latter half of the 20th century when recurrence rates were approximately 20% and relapses detected up to 20-30 years after surgery. Since then, however, diagnosis, treatment, and postoperative monitoring of PTC patients have evolved significantly., Objectives: The objective of the study was to identify times to PTC recurrence and rates by which these relapses occurred in a more recent patient cohort., Patients and Design: We retrospectively analyzed follow-up data for 1020 PTC patients consecutively diagnosed in 1990-2008 in 8 Italian hospital centers for thyroid disease. Patients underwent thyroidectomy, with or without radioiodine ablation of residual thyroid tissue and were followed up with periodic serum thyroglobulin assays and neck sonography., Results: At the initial posttreatment (≤ 12 months) examination, 948 patients had no structural/functional evidence of disease. During follow-up (5.1-20.4 years; median 10.4 years), recurrence (cervical lymph nodes, thyroid bed) was diagnosed in 13 (1.4%) of these patients. All relapses occurred 8 or fewer years after treatment (10 within the first 5 years, 6 within the first 3 years). Recurrence was unrelated to the use/omission of postoperative radioiodine ablation., Conclusion: In PTC patients whose initial treatment produces disease remission (no structural evidence of disease), recurrent disease is rare, and it usually occurs during the early postoperative period. The picture of recurrence timing during the follow-up provides a foundation for the design of more cost-effective surveillance protocols for PTC patients.

Context: Serum thyroglobulin (Tg) assays are considered fundamental in postoperative surveillance of differentiated thyroid cancer (DTC) patients. However, the postsurgical profile of Tg levels has never been specifically investigated in patients who do not undergo radioiodine remnant ablation (RRA)., Objectives: Our objective was to explore the evolution of Tg levels over time in DTC patients treated with total or near-total thyroidectomy without RRA., Design: We retrospectively analyzed 290 consecutively diagnosed cases of low-risk (American Thyroid Association criteria) DTC treated with thyroidectomy alone and followed yearly with neck ultrasonography and serum Tg assays. We compared final Tg values in this group and a matched group of 495 RRA-positive patients. Temporal trends of serial Tg levels were also analyzed in 78 of the RRA-negative patients monitored with a high-sensitivity immunoradiometric assay., Results: After follow-up of 2.5-22 yr (median 5 yr), final Tg levels were undetectable (<1 ng/ml) in 274 of 290 RRA-negative patients (95%) and 492 of 495 RRA-positive controls (99%). In the subset of 78 RRA-negative patients, undetectable Tg levels (<0.2 ng/ml) were recorded in 60% at the first postoperative evaluation (3-12 months) and in 79% after 5 yr. Tg levels increased in the single patient who experienced disease recurrence during the observation period., Conclusion: In most RRA-negative patients, postoperative serum Tg values spontaneously drop to undetectable levels within 5-7 yr after thyroidectomy. Thus, in later phases, Tg assays may be a valuable tool for follow-up even in patients who do not undergo RRA.

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.

Context: Most papillary thyroid microcarcinomas (PTMCs; ≤ 1 cm diameter) are indolent low-risk tumors, but some cases behave more aggressively. Controversies have thus arisen over the optimum postoperative surveillance of PTMC patients., Objectives: We tested the hypothesis that clinical criteria could be used to identify PTMC patients with very low mortality/recurrence risks and attempted to define the best strategy for their management and long-term surveillance., Design: We retrospectively analyzed data from 312 consecutively diagnosed PTMC patients with T1N0M0 stage disease, no family history of thyroid cancer, no history of head-neck irradiation, unifocal PTMC, no extracapsular involvement, and classic papillary histotypes. Additional inclusion criteria were complete follow-up data from surgery to at least 5 yr after diagnosis. All 312 had undergone (near) total thyroidectomy [with radioactive iodine (RAI) remnant ablation in 137 (44%) - RAI group] and were followed up yearly with cervical ultrasonography and serum thyroglobulin, TSH, and thyroglobulin antibody assays., Results: During follow-up (5-23 yr, median 6.7 yr), there were no deaths due to thyroid cancer or reoperations. The first (6-12 months after surgery) and last postoperative cervical sonograms were negative in all cases. Final serum thyroglobulin levels were undetectable (<1 ng/ml) in all RAI patients and almost all (93%) of non-RAI patients., Conclusion: Accurate risk stratification can allow safe follow-up of most PTMC patients with a less intensive, more cost-effective protocol. Cervical ultrasonography is the mainstay of this protocol, and negative findings at the first postoperative examination are highly predictive of positive outcomes.

Objective: To evaluate the role of 24 h/4 h uptake ratio (UR) in response to radioiodine-131 ((131)I) therapy in patients with autonomously functioning thyroid nodules (AFTN)., Methods: A total of 1402 consecutive hyperthyroid patients were treated with (131)I, between 1958 and 2005. Therapeutic doses (D) were calculated according to the formula: D = weight of nodule x dose per gram of nodular tissue (q)/24 h (131)I uptake. The ratios of the 24 and 4 h uptake were retrospectively calculated and the patients were grouped according to outcome and q into three groups of UR (< or =1.25; 1.26-1.68; > or =1.69) by means of terziles., Results: Of the 1402 patients, 95 did not respond to (131)I treatment while 93/1307 developed hypothyroidism. Most non-responders (55.8%) had UR < or =1.25, while many hypothyroid patients (66.7%) had UR > or =1.69 (chi (2): P < 0.001). As q increased, the proportion of successfully treated patients increased (level of significance) only in the group with UR < or =1.25; while in the other two terziles, with increasing dose per gram of nodular tissue, the number of successfully treated patients did not increase (level of significance). The cumulative incidence of hypothyroidism was 2.2% at the 1st year after (131)I treatment, increasing to 13.9% at 5 years and 26.2% at 10 years., Conclusions: The (131)I UR can predict the outcome of (131)I treatment in AFTN and may have utility in modifying treatment in some patients to limit post-radioiodine induced hypothyroidism and treatment failures in order to achieve euthyroidism.

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.

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.

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.

Background: Differentiated papillary thyroid cancer is mostly sporadic, but the recurrence of the familial form has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer., Objective: The aim of our work was to study the telomere-telomerase complex in the peripheral blood of patients with familial papillary thyroid cancer (FPTC), including the measurement of relative telomere length (RTL), telomerase reverse transcriptase (hTERT) gene amplification, hTERT mRNA expression, telomerase protein activity, and search of hTERT or telomerase RNA component gene mutations., Patients: Cumulating a series of patients seen at the University of Siena and a series at the University of Rome, the experiments were conducted in 47 FPTC patients, 75 sporadic papillary thyroid cancer (PTC) patients, 20 patients with nodular goiter, 19 healthy subjects, and 20 unaffected siblings of FPTC patients., Results: RTL, measured by quantitative PCR, was significantly (P < 0.0001) shorter in the blood of FPTC patients, compared with sporadic PTCs, healthy subjects, nodular goiter subjects, and unaffected siblings. Also by fluorescence in situ hybridization analysis, the results confirmed shorter telomere lengths in FPTC patients (P = 0.01). hTERT gene amplification was significantly (P < 0.0001) higher in FPTC patients, compared with the other groups, and in particular, it was significantly (P = 0.03) greater in offspring with respect to parents. hTERT mRNA expression, as well as telomerase activity, was significantly higher (P = 0.0003 and P < 0.0001, respectively) in FPTC patients, compared with sporadic PTCs. RTL, measured in cancer tissues, was shorter (P < 0.0001) in FPTC patients, compared with sporadic PTCs. No mutations of the telomerase RNA component and hTERT genes were found., Conclusion: Our study demonstrates that patients with FPTC display an imbalance of the telomere-telomerase complex in the peripheral blood, characterized by short telomeres, hTERT gene amplification, and expression. These features may be implicated in the inherited predisposition to develop FPTC.

Context: Type 2 deiodinase (D2) converts T4 in T3 in several human tissues, including hypothalamus and pituitary, and, therefore, plays a pivotal role in the negative feedback regulation of TSH secretion. A common variant of the gene, threonine (Thr) 92 alanine (Ala), has been identified and associated with decreased D2 enzymatic activity., Objective: Our objective was to investigate whether this polymorphism predicts the T4 dosage needed to obtain target TSH levels in thyroidectomized patients., Setting: Ambulatory patients were included in the study., Patients: A total of 191 consecutive thyroid cancer patients, previously treated by near total thyroidectomy and radioiodine ablation, were studied. They were on stable T4 dose treatment aimed at obtaining either suppressed (supp) (n=117, <0.1 mU/liter) or near-supp (n=74, >or=0.1<0.5 mU/liter) serum TSH levels., Main Outcome Measures: DNA genotyping for D2 Thr92Ala variant and evaluation of T4 dose (microg/kg) needed to obtain target TSH levels were determined., Results: Ala/Ala homozygous patients needed a higher T4 dose as compared with patients carrying the Thr92 variant (X/Thr patients) according to a recessive genetic model (2.08+/-0.43 vs. 1.90+/-0.35 microg/kg; P<0.05). This difference was observable in the near-supp group (P=0.002), but not in the supp group (P=0.4)., Conclusions: D2 Thr92Ala polymorphism seems to predict the need for higher T4 intake in thyroidectomized patients. If this finding is confirmed in additional studies, it may predict the T4 requirement to suppress TSH on the basis of the individual genetic background.

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.

Recombinant human TSH (rhTSH) has been recently suggested for radioiodine ablation in patients with differentiated thyroid cancer (DTC). To date, studies are still not available about the effectiveness of rhTSH stimulation depending on the age, since serum TSH clearance may be different in younger and in older patients. The aim of this study was to investigate the influence of age to serum TSH levels after rhTSH stimulation and thyroid hormone withdrawal (THW). We retrospectively evaluated two groups of consecutive DTC patients: group 1 (311 patients, age 49.0+/-13.6 years, ranging 15-86) underwent rhTSH stimulation 6-12 months after thyroid ablation (rhTSH-group); group 2 (84 patients, age 46.9+/-13.5 years, ranging 20-77) was followed by THW (THW-group). The influence of age, gender, body mass index and body surface area to serum TSH levels were evaluated in both groups. RhTSH-group: on day 5 (d5), TSH levels were 32.7+/-21.4 microU/ml (range 0.8-136.6). By univariate analysis, d5-TSH was positively related to age (r=0.27, p=0.0001) and no correlations were found with the other parameters. At multivariate analysis, both age and gender (female) were independently associated with d5-TSH levels. THW-group: after thyroid hormone withdrawal, TSH levels were 71.1+/-36.4 microU/ml (range 8.5-200). At univariate analysis, only age was significantly and negatively related to serum TSH levels (r=-0.31, p=0.004). Our data indicate that age and gender seem to positively influence serum TSH levels after rhTSH stimulation. An opposite effect of age on serum TSH levels has been observed after THW. Therapeutic implications ((131)I-treatment) of these findings have to be better investigated in prospective studies.

Context: Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivo regulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes., Case Reports: We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed., Methods and Results: In both patients, elevated serum prolactin levels (123 ng/mL in patient 1 and 48 ng/mL in patient 2) were documented at the time when radioiodine uptake in the breast was observed. The hyperprolactinemia was due to prolonged treatment with the anti-dopaminergic neuroleptic risperidone in Case 1, and chronic renal failure in Case 2. When prolactin levels were normalized (by withdrawal of risperidone in Case 1 and with cabergoline in Case 2), breast tissue uptake was no longer evident on WBS., Conclusion: These cases provide the first documented correlation between serum levels of endogenous prolactin and radioiodine uptake by involuted breast tissue in humans.

Background: The purpose of the present study was to assess the accuracy of quantitative segmental analysis by strain rate imaging (SRI) technique during dobutamine test for detecting myocardial recovery after revascularization in patients with chronic ischemic regional left ventricular (LV) dysfunction and compare results with those of 2-dimensional echocardiography (2D) and tissue Doppler imaging (TDI) as well as rest-4 hours-24 hours redistribution thallium SPECT (Tl SPECT)., Methods and Results: Forty-one patients with chronic ischemic regional LV dysfunction (EF 29 +/- 8%) underwent dobutamine 2D/TDI/SRI and Tl SPECT before and after myocardial revascularization. The sensitivity, specificity, and accuracy for the recovery of regional LV function were 73%, 81%, and 77% for dobutamine 2D; 77%, 82%, and 80% for dobutamine TDI; 86%, 88%, and 85% for dobutamine SRI; and 94%, 76%, and 84% for Tl tomography. The area under the ROC curve (AUC), which reflects the overall performance for the prediction of recovery, was 0.79 for systolic-SR, 0.81 for Tl SPECT, 0.83 for postsystolic strain, and 0.87 for isovolumic-SR. If both systolic and postsystolic SRI indexes were combined with Tl SPECT, the AUC was improved to 0.94., Conclusions: Dobutamine SRI is more accurate than TDI in identifying hibernating myocardium. Systo-diastolic values obtained using dobutamine SRI echocardiography and values derived from nuclear perfusion techniques may be complementary in assessing myocardial viability.

Unlabelled: Hyperthyroidism in elderly patients is not to be under-evaluated, since it is characterized in such age range by particular clinical and prognostic features. Based upon literature survey and their clinical experience, the authors discuss in the present paper clinical, diagnostic and therapeutic problems of hyperthyroidism in geriatric patients., Material and Method: In the period between 1978-2003 out of 1804 patients surgically treated for thyroid disease (non neoplastic in 1470 pts.), 180 subjects presented hyperthyroidism (17%). 36 were in geriatric age-range (mean age 76 yr.; 29 females and 7 males). 26 presented a Multinodular Toxic Goiter (72.2%), whereas 9 patients complained of Plummer Adenoma (25%); only 1 patient showed Basedow disease (2.7%)., Results: As far as ASA classification, there were 7 ASA I, 27 ASA II and 2 ASA III. Compression of digestive tract and/or respiratory airway represented a surgical indication in 15 patients (41.6%). 12 (33.4%) were operated due to predominant cardiac symptoms (tachycardia, atrial fibrillation). The remaining 9 patients (25%) were treated for the concomitance of atypical symptoms of hyperthyroidism. We performed 15 total thyroidectomy, 7 "near totally", 8 sub-total, 6 hemithyroidectomy in case of Plummer adenoma. Postoperative mortality was nihil; p.o. morbidity was 5.5% for medical conditions (pneumonia) and surgery-related (1 laryngeal recurrent paralysis and 1 hypoparathyroidism) in 5.5%. Post-operative follow-up, conducted at 6 and 12 months from the operation, showed regression of hyperthyroidism and regression or improvement of all clinical symptoms complained by the patient., Conclusion: Surgical treatment seems to be the only immediate and definitive cure for hyperthyroidism. Geriatric age does not seem to be a surgical contraindication.