Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

Invited review: Iodine level in dairy products-A feed-to-fork overview.

The theme of iodine in the dairy sector is of particular interest due to the involvement and the interconnection of several stakeholders along the dairy food chain. Iodine plays a fundamental role in animal nutrition and physiology, and in cattle it is an essential micronutrient during lactation and for fetal development and the calf's growth. Its correct use in food supplementation is crucial to guarantee the animal's recommended daily requirement to avoid excess intake and long-term toxicity. Milk iodine is fundamental for public health, being one of the major sources of iodine in Mediterranean and Western diets. Public authorities and the scientific community have made great efforts to address how and to what extent different drivers may affect milk iodine concentration. The scientific literature concurs that the amount of iodine administered through animal feed and mineral supplements is the most important factor affecting its concentration in milk of most common dairy species. Additionally, farming practices related to milking (e.g., use of iodized teat sanitizers), herd management (e.g., pasture vs. confinement), and other environmental factors (e.g., seasonality) have been identified as sources of variation of milk iodine concentration. Overall, the aim of this review is to provide a multilevel overview on the mechanisms that contribute to the iodine concentration of milk and dairy products.

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment.

PURPOSE: Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). PATIENTS AND METHODS: Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. RESULTS: In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P < 0.001). The receiver operating characteristic plot analyses showed that, for bCT, the new cut-off points able to separate non-MTC from MTC patients were > 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test. CONCLUSIONS: Refined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease.

Tele-medicine versus face-to-face consultation in Endocrine Outpatients Clinic during COVID-19 outbreak: a single-center experience during the lockdown period.

CONTEXT: The COVID-19 outbreak in Italy is the major concern of Public Health in 2020: measures of containment were progressively expanded, limiting Outpatients' visit. OBJECTIVE: We have developed and applied an emergency plan, tailored for Outpatients with endocrine diseases. DESIGN: Cross-sectional study from March to May 2020. SETTING: Referral University-Hospital center. PATIENTS: 1262 patients in 8 weeks. INTERVENTIONS: The emergency plan is based upon the endocrine triage, the stay-safe procedures and the tele-Endo. During endocrine triage every patient was contacted by phone to assess health status and define if the visit will be performed face-to-face (F2F) or by tele-Medicine (tele-Endo). In case of F2F, targeted stay-safe procedures have been adopted. Tele-Endo, performed by phone and email, is dedicated to COVID-19-infected patients, to elderly or frail people, or to those with a stable disease. MAIN OUTCOME MEASURE: To assess efficacy of the emergency plan to continue the follow-up of Outpatients. RESULTS: The number of visits cancelled after endocrine triage (9%) is lower than that cancelled independently by the patients (37%, p < 0.001); the latter reduced from 47 to 19% during the weeks of lockdown (p = 0.032). 86% of patients contacted by endocrine-triage received a clinical response (F2F and tele-Endo visits). F2F visit was offered especially to young patients; tele-Endo was applied to 63% of geriatric patients (p < 0.001), visits' outcome was similar between young and aged patients. CONCLUSIONS: The emergency plan respects the WHO recommendations to limit viral spread and is useful to continue follow-up for outpatients with endocrine diseases.

Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases.

BACKGROUND: Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood. METHODS: To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA). RESULTS: We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells. CONCLUSIONS: Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC.

Bone turnover markers, BMD and TBS after short-term, high-dose glucocorticoid therapy in patients with Graves' orbitopathy: a small prospective pilot study.

PURPOSE: Chronic GC administration has numerous side effects, but little is known about the side effects of their short-term use (< 3 months)-particularly, when high doses are involved, as in the treatment of Graves' orbitopathy (GO). We investigated the effects of short-term, high-dose GC on bone turnover markers, bone mineral density (BMD), and trabecular bone scores (TBS). METHODS: Eleven patients (10 females and 1 male; median age 56 years) with active GO who were candidates for treatment with intravenous (iv) methylprednisone were consecutively enrolled. All patients were pretreated with a loading dose of 300,000 units of cholecalciferol, then given a median cumulative dose of 4.5 g (range 1.5-5.25 g) iv methylprednisone. Biochemical parameters of bone metabolism (25OHD3, PTH, P1NP, CTX and bALP) were measured at the baseline, and then 1 week and 1, 3, 6 and 12 months. BMD and TBS were obtained by X-ray absorptiometry (DXA) at the baseline and at 6 and 12 months. On DXA image, morphometric vertebral fracture assessment (VFA) was done. RESULTS: There were no significant changes in PTH, bALP or P1NP. A significant drop in CTX was seen at 1 month (down Δ49.31% from the baseline, p = 0.02), with a return to the baseline at the 3-month measurement. There was a moderate (not significant), but persistent reduction in P1NP. No changes in BMD or TBS came to light. No vertebral fractures were documented. CONCLUSIONS: Short-term, high-dose GC treatment caused a rapid, transient suppression of bone resorption, with no effects on BMD or bone micro-architecture (TBS).

PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.

Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.

Selective inhibitors of aurora kinases inhibit proliferation, reduce cell viability and impair cell cycle progression in papillary thyroid carcinoma cells.

The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC50 comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC.

The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma.

BACKGROUND: BRAF(V600E) mutation, which represents the most frequent genetic mutation in papillary thyroid carcinoma (PTC), is widely considered to have an adverse outcome on PTC outcome, however its real predictive value is not still well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation could be useful to identify within patients with intrathyroid ultrasound-N0 PTC those who require more aggressive treatment, by central neck node dissection (CLND) or subsequent postoperative (131)I treatment. METHODS: Among the whole series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of University of Padova and at General Surgery Department of University of Trieste during a period from January 2007 to December 2012, we selected 226 patients with an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0). BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. We analyzed the correlation between the presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA) and the clinical-pathological features: age, gender, extension of surgery, node dissection, rate of cervical lymph node involvement, tumor size, TNM stage, variant of histotype, mono/plurifocality, association with lymphocitary chronic thyroiditis, radioactive iodine ablation doses, and outcome. RESULTS: The BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E) mutation correlated with multifocality, more aggressive variants, infiltration of the tumoral capsule, and greater tumor's diameter. BRAF(V600E) mutation was the only poor prognostic factor in these patients. DISCUSSION: In our series, BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of disease and it could be useful in the management of low-risk PTC patients, as supplementary prognostic factor to assess the preoperative risk stratification with the aim to avoid unnecessary central neck node dissection (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.).

Functional significance of the novel H-RAS gene mutation M72I in a patient with medullary thyroid cancer.

Medullary thyroid cancer (MTC) accounts for around 5-10% of all thyroid cancers. Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones.This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance.Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS, 1 with the Q61R mutation in H-RAS, 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I.Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding. Results of molecular dynamics were consistent with Western blot experiments.The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. This work underscores the importance of studying genetic alterations that may lead to carcinogenesis.

Validation of RiskCheck Bladder Cancer ©, version 5.0 for risk-adapted screening of bladder cancer.

INTRODUCTION: The aim of the study was to assess the strength of the online tool RiskCheck Bladder Cancer©, version 5.0 (RCBC) for early detection of bladder cancer (BC). MATERIALS AND METHODS: RCBC was evaluated retrospectively based on the data of 241 patients, of which 141 were suffering from BC. Statistical analysis was performed by descriptive statistics, nonparametric group comparison, classification tree analysis and ROC analysis. RESULTS: ROC analysis of the risk classification showed a sensitivity of 71.6%, a specificity of 56.5%, a positive predictive value of 67.8%, a negative predictive value of 52% and an accuracy of 63.5%. BC risk factors ranked by importance are time of smoking (p < 0.0001), gender (within the nonsmoking group: p < 0.009), occupational toxin exposure (within the group <35 years of smoking: p < 0.048) and amount of consumed cigarettes resulting in a 95% association with BC (within the group >35 years of smoking: p < 0.0001). CONCLUSIONS: The high predictive power of RCBC for the identification of asymptomatic patients living under risk could be demonstrated.

Iodine status in schoolchildren living in northeast Italy: the importance of iodized-salt use and milk consumption.

BACKGROUND: The aims of the study were: (i) to determine iodine status of schoolchildren living in northeast Italy; (ii) to assess dietary habits and iodine status and (iii) to investigate the level of knowledge concerning iodine sufficiency and ways to ameliorate iodine status. METHODS: One thousand three hundred seventy-five consecutive 12-13 year-old completed questionnaires collecting demographic data and information about the use of iodized salt and food frequency habits. Iodine concentration in urine samples (UIC) and in commercially available milk samples has been measured. RESULTS: The median UIC was found to be 81 µg/l (95% confidence interval (CI) 74-87); 40% of the subjects had an UIC of ≥ 100 µg/l. Iodine deficiency was prevalent in subjects living in hilly areas. Median iodine concentration in milk was 264 µg/l. Only the combined use of iodized salt plus daily milk normalized UIC, resulting into a median value of 108 µg/l. A logistic regression model confirmed independent associations between low UIC and low intake of milk, use of non-iodized salt and geographical location (P<0.0001). Only 45% of the subjects were aware of the importance of iodine. CONCLUSIONS: Northeast Italy is still characterized by mild iodine deficiency. An adequate iodine status was achieved only when iodized salt was combined with daily milk intake. The national iodine prophylaxis program has led to greater consumption of iodized salt and, it is now used in 60-70% of the Italian households. The low level of awareness highlights the need for public programs to promote knowledge and efforts to improve iodine status.

Selenium and autoimmune thyroiditis.

Selenium (Se) takes part in the activation and deactivation of thyroid hormones as a component of the catalytic site of selenodeiodinases and plays an important role in thyroid protection against oxidative damage. Based on these assumptions, in the last 10 years, several clinical trials have evaluated the effects of Se supplementation in patients with autoimmune thyroid disease (AIT) with not conclusive results. This review aims to analyze the effects of Se supplementation in patients with AIT considering studies published on this subject, so far. The emphasis is especially given on the multifactorial genesis of Hashimoto's thyroiditis (HT), which can affect the action of selenoproteins, and on the poor correlation between thyroid structural damage in HT, measurable by ultrasound examination, and antibody titer, suggesting possible recommendations for future studies.

Galectin-3 expression in thyroid fine needle cytology (t-FNAC) uncertain cases: validation of molecular markers and technology innovation.

Thyroid cancer is not very common, accounting for 1-2% of all cancers, with a population incidence of about 0.004%. Currently, the ability to discriminate between follicular adenoma and carcinoma represents the major challenge in preclinical diagnosis of thyroid proliferative lesions. Better discrimination between the two would help avoid unnecessary thyroidectomy and save valuable resources. Over the years, galectin-3 (Gal-3) has been proposed as a diagnostic marker with varied success. In this paper, we used Environmental Scanning Electron Microscopy Immunogold Labelling (ESEM-IGL) to investigate the expression of Gal-3 on Thin-Prep fine needle aspiration cytology (FNAC). We optimized the ESEM-IGL method on thyroid cell lines (RO-82 and FTC-133) comparing our membrane Gal-3 labeling data with Western blot. We evaluated 183 thyroid FNAC from Italian patients with a uncertain pre-surgical diagnosis. ESEM-IGL method marker sensitivity is 71.2%, while specificity is 53.3% and diagnostic efficacy is 61.2%. Our results confirmed that Gal-3 expression is associated with situations of hypertrophy and/or cellular hyperproliferation, pathophysiological situations common both to adenomas and to thyroid carcinomas. The innovation of thyroid FNAC Thin-Prep ESEM-IGL shows the levels of Gal-3 immunolabeling clearly, even through the individual cells of a thyroid nodule. However, Gal-3 alone, as a molecular marker of thyroid cancer, can still have a limited application in pre-surgery diagnosis.

Positive urine cytology and carcinoma in situ prior to second transurethral resection of the bladder correlate with positive second resection histology and the need for subsequent cystectomy.

OBJECTIVE: A second transurethral resection of the bladder (TURB) is recommended for high-grade bladder cancer (BC) yet yields negative results in over half of the cases. Aim of this study was to identify prognostic indicators of a positive second TURB or the need for a subsequent cystectomy. MATERIALS AND METHODS: The study cohort consisted of 101 patients with high-risk BC (T1G2-3, TaG3, Carcinoma in situ) who underwent second TURB after complete first resection. Age, gender, stage, grade, carcinoma in situ (Cis), tumour number, size, localization, surgeon experience and bladder wash cytology before the second TURB were considered as potential prognostic factors of positive histology at second TURB or the need for subsequent cystectomy. RESULTS: The mean follow-up period was 23.8 months. The study cohort was comprised of 82 males and 17 females. Cytology on bladder wash urine was performed in 85/101 patients and in 39 was negative; 55.5 % of second TURB specimens were negative. The rate of upstaging to ≥T2 was 4.9 %. Cis (OR 8.4; 95 % CI 1.3-54.2; p = 0.03) and positive cytology (OR 6.8; 95 % CI 2.3-19.9; p = <0.01) were independent prognostic factors of a residual tumour in the second TURB. Cytology also correlated with clinical need for cystectomy in the follow-up (HR 6.5; 95 % CI 1.3-30.5; p = 0.02). CONCLUSIONS: CIS and positive cytology prior to second TURB increased the risk of a positive second TURB specimen. A positive cytology also increases the risk of the subsequent need for cystectomy.

Effects of selenium supplementation on the natural course of autoimmune thyroiditis: a short review.

Selenium (Se) is an important element that exerts its effects on the selenoproteins. It is an essential component of the glutathione peroxidase enzymes, which have anti-oxidant and anti-inflammatory properties, and a component of iodothyronine selenodeiodinases, which catalyze the extrathyroid production of T3 from T4. Se is important to several aspects of thyroid homeostasis and may influence the natural course of thyroid diseases such as autoimmune thyroiditis (AIT). This review analyzes the effects of Se supplementation in patients with AIT, based on the studies published on this issue to date.

Clinical outcome of low-risk differentiated thyroid cancer patients after radioiodine remnant ablation and recombinant human thyroid-stimulating hormone preparation.

AIM: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved in Europe as a preparation tool for radioiodine ablation of post-surgical thyroid remnants in patients with low-risk differentiated thyroid cancer (DTC). Published studies report that, both thyroid hormone withdrawal and rhTSH preparation result in similar rates of successful remnant ablation, but few studies have determined the effectiveness of rhTSH preparation on disease recurrence. We sought to determine the clinical outcome, considering both ablation success and disease recurrence, of low-risk DTC patients who underwent (131)I ablation. MATERIALS AND METHODS: This retrospective study describes the clinical outcome of 100 patients treated with (131)I remnant ablation after preparation with rhTSH. After ablation, patients were classified as in complete remission, as having no evidence of persistent disease, or as having clinical recurrence on the basis of a subsequent diagnostic whole body scan with (131)I, stimulated thyroglobulin and cross-sectional imaging studies. RESULTS: Overall assessment of ablation success was verified and obtained in 75% of patients (75/100). Considering only patients who underwent a diagnostic whole body scan and stimulated thyroglobulin without interfering anti-thyroglobulin antibody, complete ablation was obtained in 96% of patients (75/78). After a follow-up of about 4 years, 78 patients are in complete remission: 75 with initial ablation success and three who achieved a complete remission during subsequent follow-up. Among the remaining 22 patients, 21 have no clinical evidence of disease (NCED), indicating the inability to verify the complete remission or to detect residual disease, as in patients with positive thyroglobulin antibody, whereas one has persistent disease demonstrated only by stimulated thyroglobulin. No recurrences were observed. Of four patients initially classified as having persistent disease, one obtained a complete remission and two are now considered NCED. CONCLUSION: Our data confirm the favourable outcome, with low rates of recurrence and persistent disease, of patients with low-risk DTC who underwent (131)I ablation after rhTSH. Moreover, our results compare favourably with those reported in the literature in patients prepared with rhTSH, but also in patients prepared with hormone withdrawal.

Diagnosis, treatment, prognostic factors and long-term outcome in papillary thyroid carcinoma.

The papillary thyroid carcinoma (PTC) is the most frequent endocrine cancer and it is the most common thyroid cancer (85-95%). Potential risk factors for the incidence of the PTC include radiation exposure, iodine deficiency, family history of thyroid cancer. The PTC is usually indolent and the prognosis is favourable, with a 10 year survival generally reported to exceed 90%. The palpation and growth of thyroid nodules are the more frequent clinical manifestations of the PTC which can be evaluated by physical examination, neck ultrasound and fine needle aspiration cytology (FNAC). The therapeutic management of PTC includes surgical treatment combined with 131I therapy and life long TSH suppressive thyroid hormone replacement. The external beam radiation can be taken into account in select aggressive tumours. Nevertheless the good prognosis of the PTC, the prevalence of persistence or recurrent disease is not trans-curable. The biomolecular studies can permit to individuate the more aggressive PTC subtypes. A more significant attention of the clinical examination, US and FNAC to the thyroid nodular disease will be able to guarantee a more precocious diagnosis and a radical surgical treatment.

Multiprobe fluorescence in situ hybridisation: prognostic perspectives in superficial bladder cancer.

AIM: To establish independent prognostic factors on a chromosomal basis in superficial bladder cancer, using a multicolour fluorescence in situ hybridisation (FISH) probe mix. PATIENTS AND METHODS: In 2002, voided urine from 75 consecutive patients (mean age 71.7, range 52-93) years under follow-up for superficial urothelial cancer was studied prospectively. The patients were observed for a mean (standard deviation (SD)) period of 39.3 (6.8) months (range 27-58) until July 2005. A multicolour FISH on liquid-based voided urinary cytology was carried out on all patients. Univariate analysis, using a log rank test, was used to determine the prognostic relevance of a low-risk pattern and a high-risk pattern. Progression-free survival time was calculated from the date of first diagnosis to first recurrence or progression according to the Kaplan-Meier product-limit method. RESULTS: One patient was lost to follow-up. 27 of the 74 remaining (36.8%) patients showed recurrent disease. In 9 (33.3%) patients with a low-risk pattern disease recurred after a mean (SD) observation time of 29.7 (1.9) months (range 8.3-52.3, median 30.8 (12.4)). 18 (66.7%) patients with a high-risk pattern developed recurrence within a mean (SD) of 17.6 (2.0) months (range 4-38.8, median 16.7 (11.6)). The Kaplan-Meier curve for progression-free survival showed marked differences between the low-risk and the high-risk groups. CONCLUSION: Patients with a high-risk chromosomal pattern have a markedly shorter disease-free survival time and higher progression rate than patients with a low-risk pattern. High-risk patients can therefore be treated more aggressively to prevent tumour spreading.