Dietary selenium intake and thyroid cancer risk in postmenopausal women.

OBJECTIVE: It has been suggested that higher selenium intake and consumption of supplements protect against several cancers. To our knowledge, epidemiologic evidence is rare and inconsistent on the association of selenium level and the risk for thyroid cancer. Therefore, the aim of this study was to examine the association between selenium intake and thyroid cancer risk in postmenopausal women using the Women's Health Initiative (WHI) database. METHODS: The WHI recruited 161 808 postmenopausal women 50 to 79 y of age between September 1, 1993 and December 31, 1998. The present study included 147 348 women 63.15 y of age (SD = 7.21) at baseline. The main exposure was baseline total selenium intake including dietary selenium measured by food frequency questionnaire (FFQ) and supplemental selenium. The outcome was thyroid cancer, which was adjudicated by trained physicians. Cox proportional hazard models were used to analyze the association. RESULTS: During a mean follow-up of 16.4 y until September 30, 2020, 442 thyroid cancer cases were identified. There was no significant association between total selenium intake and thyroid cancer risk after adjusting for multiple covariates (highest versus lowest quartile: hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.60-1.29). Association between total selenium intake and the risk for papillary thyroid cancer was also not significant (highest versus lowest quartile: HR, 1.02; 95% CI, 0.66-1.52). CONCLUSIONS: The present data did not support that either total or dietary selenium intake was associated with the risk for thyroid cancer or the papillary subtype in postmenopausal women ages 50 to 79 y in the United States.

The Iodine Rush: Over- or Under-Iodination Risk in the Prophylactic Use of Iodine for Thyroid Blocking in the Event of a Nuclear Disaster.

Iodine is an essential element for the production of thyroid hormones (THs). Both deficient and excess iodine intakes may precipitate in adverse thyroidal events. Radioactive iodine (RI) is a common byproduct of nuclear fission processes. During nuclear emergencies RI may be released in a plume, or cloud, contaminating the environment. If inhaled or ingested, it may lead to internal radiation exposure and the uptake of RI mainly by the thyroid gland that absorbs stable iodine (SI) and RI in the same way. A dose of radiation delivered to the thyroid gland is a main risk factor for the thyroid cancer development. The SI prophylaxis helps prevent childhood thyroid cancer. The thyroid gland saturation with prophylactic SI ingestion, reduces the internal exposure of the thyroid by blocking the uptake of RI and inhibiting iodide organification. However, negative impact of inadequate SI intake must be considered. We provide an overview on the recommended iodine intake and the impact of SI and RI on thyroid in children and adolescents, discussing the benefits and adverse effects of the prophylactic SI for thyroid blocking during a nuclear accident. The use of SI for protection against RI may be recommended in cases of radiological or nuclear emergencies, moreover the administration of iodine for prophylactic purposes should be cautious. Benefits and risks should also be considered according to age. Adverse effects from iodine administration cannot be excluded. Precise indications are mandatory to use the iodine for thyroid blocking. Due to this natural adaption mechanism it's possible to tolerate large doses of iodine without clinical effects, however, a prolonged assumption of the iodine when not needed can be dangerous and may precipitate in severe thyroidal and non-thyroidal negative effects.

A comparison of thyroidal protection by iodine and perchlorate against radioiodine exposure in Caucasians and Japanese.

Radioactive iodine released in nuclear accidents may accumulate in the thyroid and by irradiation enhances the risk of cancer. Radioiodine uptake into the gland can be inhibited by large doses of stable iodine or perchlorate. Nutritional iodine daily intake may impact thyroid physiology, so that radiological doses absorbed by the thyroid as well as thyroid blocking efficacy may differ in Japanese with a very rich iodine diet compared to Caucasians. Based on established biokinetic-dosimetric models for the thyroid, we derived the parameters for Caucasians and Japanese to quantitatively compare the effects of radioiodine exposure and the protective efficacy of thyroid blocking by stable iodine at the officially recommended dosages (100 mg in Germany, 76 mg in Japan) or perchlorate. The maximum transport capacity for iodine uptake into the thyroid is lower in Japanese compared to Caucasians. For the same radioiodine exposure pattern, the radiological equivalent thyroid dose is substantially lower in Japanese in the absence of thyroid blocking treatments. In the case of acute radioiodine exposure, stable iodine is less potent in Japanese (ED50 = 41.6 mg) than in Caucasians (ED50 = 2.7 mg) and confers less thyroid protection at the recommended dosages because of a delayed responsiveness to iodine saturation of the gland (Wolff-Chaikoff effect). Perchlorate (ED50 = 10 mg in Caucasians) at a dose of 1000 mg has roughly the same thyroid blocking effect as 100 mg iodine in Caucasians, whereas it confers a much better protection than 76 mg iodine in Japanese. For prolonged exposures, a single dose of iodine offer substantially lower protection than after acute radioiodine exposure in both groups. Repetitive daily iodine administrations improve efficacy without reaching levels after acute radioiodine exposure and achieve only slightly better protection in Japanese than in Caucasians. However, in the case of continuous radioiodine exposure, daily doses of 1000 mg perchlorate achieve a high protective efficacy in Caucasians as well as Japanese (> 0.98). In Caucasians, iodine (100 mg) and perchlorate (1000 mg) at the recommended dosages seem alternatives in case of acute radioiodine exposure, whereas perchlorate has a higher protective efficacy in the case of longer lasting radioiodine exposures. In Japanese, considering protective efficacy, preference should be given to perchlorate in acute as well as prolonged radioiodine exposure scenarios.

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common subtype of differentiated thyroid cancers in Asian coastal cities, where the patients have increased risk of potentially high or excessive iodine intake. Given the high metastasis and recurrence of patients with BRAFV600E mutation, the mortality rate of thyroid cancer has recently shown an upward trend. A variety of therapies, including surgery, radiotherapy, and chemotherapy, have been used to treat thyroid cancer, but these therapies still have limitations, including postoperative complications, drug resistance, poor efficacy, or serious side effects. Recent studies have shown the potential of active ingredients derived from herbal medicine in inhibiting PTC via various cell signaling pathways. Some plant-derived compounds, such as apigenin, genistein, and curcumin, are also known to prevent and treat PTC. This article summarizes the recent advances in the structure-functional impact of anti-PTC active ingredients and their effects on PTC cells and tumor microenvironments with an emphasis on their challenges from basic research to clinical practice.

Phytoestrogens and Thyroid Cancer Risk: A Population-Based Case-Control Study in Connecticut.

BACKGROUND: Very few previous studies have examined the relationship between thyroid cancer risk and intake of phytoestrogens (PE); furthermore, these studies have reached inconsistent results. METHODS: We analyzed data from a population-based case-control study in Connecticut from 2010 to 2011, including 387 histologically confirmed thyroid cancer cases and 433 population-based controls, with compound data available concerning specific PEs. Multivariate unconditional logistic regression models were used to estimate the associations between specific PEs and the risk of thyroid cancer, adjusting for potential confounders. RESULTS: An elevated risk of thyroid cancer was associated with moderate to high levels of coumestrol intake [OR = 2.48, 95% confidence interval (CI), 1.39-4.43 for 40-80 µg/day; OR = 2.41, 95% CI, 1.32-4.40 for 80-130 µg/day; and OR = 2.38, 95% CI, 1.26-4.50 for >200 µg/day compared with <40 µg/day], and the main elevation in risk appeared among microcarcinomas (≤1 cm). A decreased risk of papillary macrocarcinomas (>1 cm; OR = 0.26, 95% CI, 0.08-0.85 for 1,860-3,110 µg/day compared with <760 µg/day) was associated with moderate genistein intake among women. CONCLUSIONS: Our study suggests that high coumestrol intake increases the risk of thyroid cancer, especially microcarcinomas, whereas moderate amounts of genistein intake appear to be protective for females with thyroid macrocarcinomas. IMPACT: The study highlights the importance of distinguishing between microcarcinomas and macrocarcinomas in future research on the etiology of thyroid cancer.

MiR-141-3p Suppresses Tumor Growth and Metastasis in Papillary Thyroid Cancer via Targeting Yin Yang 1.

MicroR-141-3p has been found to be downregulated in papillary thyroid carcinoma (PTC), while little is known about the cellular functions and precise signals elicited by miR-141-3p in PTC. The results of this study indicated that the expression of miR-141-3p was aberrantly down-regulated in PTC tissues and cell lines, compared with the adjacent normal tissues and normal thyroid epithelial cells. Furthermore, the miR-141-3p expression level was negatively associated with TNM stage and lymph node metastasis in PTC. Expression of miR-141-3p effectively inhibited cell growth, promoted apoptosis, and suppressed invasion in PTC cells. Meanwhile, miR-141-3p knockdown with miR-141-3p inhibitor reversed these effects. Consistent with the in vitro study, miR-141-3p also exhibited anti-neoplastic activity in vivo. Moreover, the results revealed that miR-141-3p directly recognized the 3' untranslated region (3'UTR) of Yin Yang 1 (YY1) and negatively regulated the expression of YY1 at both protein and mRNA levels. Ectopic expression of YY1 could effectively abrogate the anti-metastatic and proapoptotic effects of miR-141-3p. In summary, the findings suggested that miR-141-3p can act as a tumor suppressor in PTC and may be a potential therapeutic target for PTC treatment. Anat Rec, 302:258-268, 2019. © 2018 Wiley Periodicals, Inc.

Iodine Prophylaxis in the Case of Nuclear Accident.

BACKGROUND: On 26th April, 1986 the greatest accident of nuclear plant in Czernobyl occured and isotopes with high percentage of release were erupted: 33-Xe, 131-I, 132-Te, 134-Cs and 137-Cs. The radioactivity of the isotopes was very high - for instance: 33-Xe 6500 PBq, 131-I 1760 PBq. Rest of the 15 isotopes represented similar radioactivity with shorter percentage of release. The most exposed group of people were 237 liquidators, and 11600 people living around had to be evacuated when the limit dose for a person (5mSv) was crossed. Ionizing radiation on the molecular level produces high energy radicals, water radiolysis and ionization of the atoms leading to damage of the enzymes activity centers and receptors, cell membranes DNA, intracellular lysosomes, and especially important for ATP synthesis - mitochondria. These destructions lead to tissue and organs damage. OBJECTIVE: The aim of this article is the presentation of the protective property of iodine application in the case of nuclear accident. METHODS: In Poland at that time, effective iodine prophylaxis did not exist. In the face of such exposition, a special Governement Commission was appointed. When permissioned maximal dose for children and adolescents 50mSv appeared in some areas of the country, the Commission made a decision about obligatory administration of a single pharmacological dose of potassium iodide for all children and adolescents till age 16. No relevant recent patents were available for this WHO report. RESULTS: In this way, the dose of 131-I to thyroid for inhabitants in high, moderated, and low contaminated regions were reduced by about 45%. However, from 1987 to 1997 increase in prevalence of the differentiated thyroid cancer in adults in Polish population especially in women over 40 years old in the southern part of Poland was observed. CONCLUSION: Actually in European countries work 185 nuclear power plants and to 2045 another 100 is planned. In 1999, WHO issued recommendations on iodine prophylaxis in the case of nuclear accident.

Coffee Consumption and the Risk of Thyroid Cancer: A Systematic Review and Meta-Analysis.

An inverse association has been reported between coffee consumption and the risk of several cancers. However, the association between coffee and thyroid cancer is controversial. Thus, this study aimed to evaluate the association between coffee consumption and the risk of thyroid cancer through a systematic review and meta-analysis. Published studies were examined from PubMed, Embase, Cochrane Central, and the reference lists of the retrieved articles. The summary odds ratio (OR) for the association between coffee consumption was categorized as highest versus lowest consumption, and thyroid cancer risk was calculated using a fixed effects model. Subgroup analyses by study design, geographic location, source of controls, and adjusted variables were performed. A total of 1039 thyroid cancer cases and 220,816 controls were identified from five case-control studies and two cohort studies. The summary OR for the association between coffee consumption and thyroid cancer risk was 0.88 (95% confidence interval (CI) = 0.71-1.07). There was no significant heterogeneity among the study results (I² = 0%, p = 0.79). However, the beneficial effect of coffee consumption on thyroid cancer was found only in hospital-based case-control studies (OR= 0.59, 95% CI= 0.37-0.93). There was no significant association between coffee consumption and thyroid cancer risk according to our meta-analysis results. These findings should be interpreted with caution because of potential biases and confounding variables. Further prospective studies with a larger number of cases are encouraged to confirm these results.

The effect of Greek herbal tea consumption on thyroid cancer: a case-control study.

BACKGROUND: Although in the last decade several studies have addressed the protective role of black and green tea on several diseases, including cancer, there are only few and controversial studies on the effect of tea on benign and malignant thyroid diseases. METHODS: An age and gender group matched case-control study conducted in Athens, Greece, was designed. 113 Greek patients with histologically confirmed thyroid cancer and 286 patients with benign thyroid diseases along with 138 healthy controls were interviewed with a pre-structured questionnaire in person by trained interviewers. RESULTS: An inverse association between chamomile tea consumption and benign/malignant thyroid diseases was found (P < 0.001). The odds of chamomile tea consumption, two to six times a week, after controlling for age, gender and BMI, were 0.30 (95% CI: 0.10-0.89) and 0.26 (95% CI: 0.12-0.5) for developing thyroid cancer and benign thyroid diseases, respectively when compared with not consumption. The duration of consumption was also inversely associated with the diseases. Thirty years of consumption significantly reduced the risk of thyroid cancer and benign thyroid diseases development by almost 80%. Similar, although weaker protective association, was found for sage and mountain tea. Adjustment for smoking, alcohol and coffee consumption did not alter the results. CONCLUSIONS: Our findings suggest for the first time that drinking herbal teas, especially chamomile, protects from thyroid cancer as well as other benign thyroid diseases.

Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells.

A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC50 values of 121-230 µg/ml (MCF-7), 121-184 µg/ml (MDA-MD-23), 175-309 µg/ml (HT29), 159-314 µg/ml (K1), 180-225 µg/ml (786-0) and 134->400 µg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.

Effects of low-dose and high-dose postoperative radioiodine therapy on the clinical outcome in patients with small differentiated thyroid cancer having microscopic extrathyroidal extension.

BACKGROUND: It is unclear whether differentiated thyroid cancer (DTC) patients classified as intermediate risk based on the presence of microscopic extrathyroidal extension (ETE) should be treated with low or high doses of radioiodine (RAI) after surgery. We evaluated success rates and long-term clinical outcomes of patients with DTC of small tumor size, microscopic ETE, and no cervical lymph node (LN) metastasis treated either with a low (1.1 GBq) or high RAI dose (5.5 GBq). METHODS: This is a retrospective analysis of a historical cohort from 2000 to 2010 in a tertiary referral hospital. A total of 176 patients with small (≤2 cm) DTC, microscopic ETE, and no cervical LN metastasis were included. Ninety-six patients were treated with 1.1 GBq (LO group) and 80 patients with 5.5 GBq (HI group). Successful RAI therapy was defined as (i) negative stimulated thyroglobulin (Tg) in the absence of Tg antibodies, and (ii) absence of remnant thyroid tissue and of abnormal cervical LNs on ultrasonography. Clinical recurrence was defined as the reappearance of disease after ablation, which was confirmed by cytologically or pathologically proven malignant tissue or of distant metastatic lesions. RESULTS: There was no significant difference in the rate of successful RAI therapy between the LO and HI groups (p=0.75). In a subgroup analysis based on tumor size, success rates were not different between the LO group (34/35, 97%) and the HI group (50/56, 89%) in patients with a tumor size of 1-2 cm (p=0.24). In patients with smaller tumor size (≤1 cm), there was no significant difference in success rates between the LO (59/61, 97%) and HI groups (22/24, 92%; p=0.30). No patient had clinical recurrences in either group during the median 7.2 years of follow-up. CONCLUSIONS: Low-dose RAI therapy is sufficient to treat DTC patients classified as intermediate risk just by the presence of microscopic ETE.

Thyroid ablation with 1.1 GBq (30 mCi) iodine-131 in patients with papillary thyroid carcinoma at intermediate risk for recurrence.

BACKGROUND: Little is known about the medium- and long-term outcomes of thyroid ablation with 1.1 GBq (30 mCi) ¹³¹I in patients with papillary thyroid carcinoma who have a tumor >4 cm or accompanied by extrathyroid invasion or clinically detected lymph node metastases (cN1). The objective of this study was to evaluate the efficacy of ablation with 30 mCi ¹³¹I in this subgroup of patients and to report the medium-term outcomes. METHODS: We studied 152 patients with papillary thyroid carcinoma submitted to total thyroidectomy with apparently complete tumor resection, who had a tumor >4 cm or 2-4 cm accompanied by extrathyroid invasion or lymph node metastases, or ≤2 cm accompanied by both extrathyroid invasion and lymph node metastases. Patients with extensive extrathyroid invasion by the primary tumor were excluded. Lymph node involvement was detected by ultrasonography or palpation (cN1). RESULTS: Forty-two patients were prepared by administration of recombinant human thyrotropin and 110 by levothyroxine withdrawal. Posttherapy whole-body scanning revealed unequivocal ectopic uptake in three patients. When evaluated 9-12 months after ablation, 123 patients had achieved complete ablation (stimulated thyroglobulin [Tg] <1 ng/mL, negative anti-Tg antibodies, and neck ultrasonography); a new posttherapy whole-body scanning revealed persistent disease in 2 patients whose initial posttherapy whole-body scanning (obtained at the time of ablation) had already shown ectopic uptake; 12 patients presented with a Tg >1 ng/mL and 14 had positive anti-Tg antibodies without apparent metastases; 1 patient had metastases not detected at the time of ablation. Recurrence was observed in an additional 6 patients during follow-up (median 76 months). There was no case of death related to the disease. Therefore, an activity of 30 mCi failed in only 9 (6%) patients with persistent disease or recurrence after ablation. None of the variables analyzed (sex, age, tumor size, multicentricity, extrathyroid invasion, lymph node metastases, preparation [recombinant human thyrotropin or levothyroxine withdrawal]) was a predictor of ablation failure. CONCLUSIONS: An activity of 30 mCi ¹³¹I is effective in thyroid ablation in patients with stage T3 and/or N1 papillary thyroid carcinoma.

Modified dynamic risk stratification for predicting recurrence using the response to initial therapy in patients with differentiated thyroid carcinoma.

OBJECTIVE: A new risk stratification system was proposed to estimate the risk of recurrence in patients with differentiated thyroid carcinoma (DTC) using the response to initial therapy. Here, we describe the modified dynamic risk stratification system, which takes into consideration the status of serum anti-Tg antibody (TgAb), and validate this system for assessing the risk of recurrence in patients with DTC. PATIENTS AND METHODS: Patients who underwent total thyroidectomy with radioiodine remnant ablation due to DTC between 2000 and 2005 were included. We classified patients into four groups based on the response to the initial therapy ('excellent', 'acceptable', 'biochemical incomplete', and 'structural incomplete' response). RESULTS: The median follow-up period of 715 patients with DTC was 8 years. The response to initial therapy was an important risk predictor for recurrent/persistent DTC. The relative risks (95% CI) of recurrence were 16.5 (6.3-43.0) in the 'acceptable response' group, 41.3 (15.4-110.8) in the 'biochemical incomplete response' group, and 281.2 (112.9-700.5) in the 'structural incomplete response' group compared with the 'excellent response' group (P<0.001, P<0.001, and P<0.001 respectively). The disease-free survival rate of the 'excellent response' group to initial therapy was 98.3% whereas that of the 'structural incomplete response' group was only 6.8%. CONCLUSIONS: Our study validates the usefulness of the modified dynamic risk stratification system including the status of serum TgAb for predicting recurrent/persistent disease in patients with DTC. Personalized risk assessment using the response to initial therapy could be useful for the follow-up and management of patients with DTC.

Prognostic nomograms to predict oncological outcome of thyroid cancers.

CONTEXT: Thyroid cancers represent a conglomerate of diverse histological types with equally variable prognosis. There is no reliable prognostic model to predict the risks of relapse and death for different types of thyroid cancers. OBJECTIVE: The purpose of this study was to build prognostic nomograms to predict individualized risks of relapse and death of thyroid cancer within 10 years of diagnosis based on patients' prognostic factors. DESIGN: Competing risk subhazard models were used to develop prognostic nomograms based on the information on individual patients in a population-based thyroid cancer cohort followed up for a median period of 126 months. Analyses were conducted using R version 2.13.2. The R packages cmprsk10, Design, and QHScrnomo were used for modeling, developing, and validating the nomograms for prediction of patients' individualized risks of relapse and death of thyroid cancer. SETTING: This study was performed at CancerCare Manitoba, the sole comprehensive cancer center for a population of 1.2 million. PATIENTS: Participants were a population-based cohort of 2306 consecutive thyroid cancers observed in 2296 patients in the province of Manitoba, Canada, during 1970 to 2010. MAIN OUTCOME MEASURES: Outcomes were discrimination (concordance index) and calibration curves of nomograms. RESULTS: Our cohort of 570 men and 1726 women included 2155 (93.4%) differentiated thyroid cancers. On multivariable analysis, patient's age, sex, tumor histology, T, N, and M stages, and clinically or radiologically detectable posttreatment gross residual disease were independent determinants of risk of relapse and/or death. The individualized 10-year risks of relapse and death of thyroid cancer in the nomogram were predicted by the total of the weighted scores of these determinants. The concordance indices for prediction of thyroid cancer-related deaths and relapses were 0.92 and 0.76, respectively. The calibration curves were very close to the diagonals. CONCLUSIONS: We have successfully developed prognostic nomograms for thyroid cancer with excellent discrimination (concordance indices) and calibration.

The results of selective use of radioactive iodine on survival and on recurrence in the management of papillary thyroid cancer, based on Memorial Sloan-Kettering Cancer Center risk group stratification.

BACKGROUND: The American Thyroid Association guidelines recommend the routine use of radioactive iodine for remnant ablation (RRA) in all T3 or greater primary tumors, and selective use in patients with intrathyroidal disease >1 cm, or evidence of nodal metastases. The guidelines recognize that there is conflicting and inadequate data to make firm recommendations for most patients. The aim of this study was to analyze our institutional experience of the use of RRA in the management of papillary thyroid cancer, with a particular focus on outcomes for those patients selected not to receive RRA. METHODS: We retrospectively reviewed 1129 consecutive patients who underwent total thyroidectomy at the Memorial Sloan-Kettering Cancer Center between 1986 and 2005. Of these, 490 were pT1-2 N0, 193 pT1-2 N1, and 444 pT3-4. Details on recurrence and disease-specific survival were recorded by the Kaplan-Meier method and compared using the log-rank test. RESULTS: The five-year disease-specific survival and recurrence-free survival in the pT1/T2 N0, pT1-2 N1, and pT3-4 were 100% and 92%, 100% and 92%, and 98% and 87% respectively. Low-risk patients who were managed without RRA (who tended to have limited primary disease, pT1-2, and low-volume metastatic disease in the neck, pT1-2 N1-fewer than five nodes, all <1 cm greatest dimension) had five-year recurrence-free survival of >97%. In the group with advanced local tumors (pT3-4), those patients who did not receive RRA (who tended to have pT3 N0 disease) had five-year recurrence-free survival of >90%. CONCLUSION: Following appropriate surgical management, the majority of patients with low-risk local disease and even some patients with more advanced-stage (pT3) tumors or regional metastases have low rates of recurrence and high rates of survival when managed without RRA.

Long-term outcomes following low-dose radioiodide ablation for differentiated thyroid cancer.

CONTEXT: Randomized trials show that low-dose (1.1 GBq [30 mCi]) radioiodide (RAI) has efficacy equivalent to high-dose RAI (3.7 GBq [100 mCi]) in thyroid remnant ablation (TRA) for differentiated thyroid cancer. Long-term follow-up is required to ensure detection of late recurrences and to confirm equivalence in terms of survival end points. However, median follow-up duration within randomized trials is currently limited. PATIENTS AND SETTING: We studied 53 patients undergoing TRA for differentiated thyroid cancer with long-term follow-up in the Thyroid Unit of The Royal Marsden Hospital (Sutton, United Kingdom). INTERVENTION: Patients were treated with TRA using low-dose (1.1 GBq) RAI. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, and the incidence of second malignancies were measured. Multivariable analysis was used to determine clinical risk factors for failure to achieve TRA after low-dose RAI. RESULTS: Median follow-up was 24 (range, 4-34) years. Low-dose RAI TRA was successful in 26 (49%) patients (successful ablation [SA] group), whereas 27 (51%) patients required further treatment (unsuccessful ablation [UA] group). Thirty-year disease-free survival was 92% in the SA group vs 87% in the UA group (P = .601). Thirty-year overall survival was 81% in the SA group vs 62% in the UA group (P = .154). Nine (17%) patients developed second malignancies (4 in the SA group and 5 in the UA group). Predictors of failure to achieve TRA with low-dose RAI were male sex and stage pT4 disease. CONCLUSIONS: There is no evidence from long-term follow-up of our cohort that treatment outcomes are compromised for patients that fail TRA with low-dose RAI and subsequently receive high-dose RAI.

Vitamin and mineral supplements and thyroid cancer: a systematic review.

The purpose of this study was to consolidate epidemiological evidence for the association between dietary supplements of vitamins and minerals and thyroid cancer development, as well as to contribute to evidence-based dietary recommendations for thyroid cancer primary prevention. We carried out a systematic literature review specifically for dietary supplement and thyroid cancer risk. MEDLINE, EMBASE, and Dissertations and Theses were systematically searched to identify original epidemiological studies with a comparison group that investigated vitamin or mineral supplementation as an etiological factor for thyroid cancer. In total, 11 independent studies were identified and reviewed. Our qualitative summary showed conflicting results for common antioxidants including vitamins A, C, and E and ß-carotene in relation to thyroid cancer. Similarly, results for dietary supplement combinations as well as other individual vitamins and minerals (vitamin B complex, vitamin D, iodine, calcium, zinc, magnesium, and iron) are largely inconsistent across studies. Overall, our review suggested that the current evidence to support any protective or hazardous effect of vitamin or mineral supplements on thyroid cancer development is inconclusive and additional studies addressing previous limitations are necessary to elucidate this possible association. In particular, reverse causality is of major concern and should be addressed by prospective studies with large and representative samples.

Prophylactic central neck dissection for papillary thyroid cancer.

BACKGROUND: Prophylactic central neck dissection (CND) for papillary thyroid cancer (PTC) remains controversial. The aim of this study was to examine whether prophylactic CND for PTC affected long-term survival and locoregional control. METHODS: This was a retrospective cohort study of patients who underwent total thyroidectomy (TT) with bilateral prophylactic CND. They were compared with patients who had TT without CND. Personalized adjuvant radioiodine treatment was used in both groups. Primary outcomes were overall and disease-specific survival, and locoregional control. Secondary outcomes were number of patients with negative serum thyroglobulin levels, and morbidity. RESULTS: Of 640 patients with PTC included in this study, 282 (treated in 1993-1997) had TT without CND and 358 (treated in 1998-2002) underwent TT with CND. The 10-year disease-specific survival rate for patients who had TT without CND was 92·5 per cent compared with 98·0 per cent in patients with CND (P = 0·034), and the locoregional control rate was 87·6 and 94·5 per cent respectively (P = 0·003). In multivariable analysis, extrathyroidal extension was an independent predictive factor for locoregional recurrence (odds ratio 12·47, 95 per cent confidence interval 6·74 to 23·06; P < 0·001), whereas CND was an independent predictive factor for improved locoregional control at 10 years after surgery (odds ratio 0·21, 0·11 to 0·41; P < 0·001). No differences were seen in the rates of permanent hypoparathyroidism or recurrent laryngeal nerve injury between the groups. CONCLUSION: Bilateral prophylactic CND for staging of the neck in PTC, followed by personalized adjuvant radioiodine treatment, improved both 10-year disease-specific survival and locoregional control, without increasing the risk of permanent morbidity. REGISTRATION NUMBER: NCT01510002 (http://www.clinicaltrials.gov).

Selenium and cancer prevention: observations and complexity.

Early case-control and intervention studies suggested that selenium (Se) species might reduce the risk of cancer and in a pre-diagnostic case-control study from 1986 [1] we found that the higher the serum Se concentration, the lower was the odds ratio of thyroid cancer. Our data showed, however, that this observation occurred late in the pre-diagnostic period indicating that low serum Se was simply a consequence of thyroid cancer. In 1986 we therefore concluded that the only way to get an indisputable and lasting answer to the question was to carry out properly designed intervention studies. Great was our frustration therefore when we in 2003 [2] discovered that thyroid cancer morbidity is a fractal variable powered by such complexity that we may never find a definite and enduring answer: Even the best, randomised, controlled trial comparing the incidence rate among exposed and controls can only produce temporary answers due to the complexity background. The only possible way to come up with a lasting solution seems to be by means of reductionist experiments, but they have to be tested on man and then one is back to square one.

The Japanese tsunami and resulting nuclear emergency at the Fukushima Daiichi power facility: technical, radiologic, and response perspectives.

The Fukushima Daiichi nuclear power facility, in the Futaba District of the Fukushima Prefecture in Japan, was severely damaged by the earthquake and ensuing tsunami that struck off the northern coast of the island of Honshu on March 11, 2011. The resulting structural damage to the plant disabled the reactor's cooling systems and led to significant, ongoing environmental releases of radioactivity, triggering a mandatory evacuation of a large area surrounding the plant. The status of the facility continues to change, and permanent control of its radioactive inventory has not yet been achieved. The purpose of this educational article is to summarize the short-term chronology, radiologic consequences, emergency responses, and long-term challenges associated with this event. Although there is ongoing debate on preparedness before the event and the candor of responsible entities in recognizing and disclosing its severity, it largely appears that appropriate key actions were taken by the Japanese authorities during the event that should mitigate any radiologic health impact. These actions include an organized evacuation of over 200,000 inhabitants from the vicinity of the site and areas early in the emergency; monitoring of food and water and placement of radiation limits on such foodstuffs; distribution of stable potassium iodide; and systematic scanning of evacuees. However, the risk of additional fuel damage and of further, perhaps substantial, releases persists. The situation at the Fukushima Daiichi nuclear facility remains fluid, and the long-term environmental and health impact will likely take years to fully delineate.