Extra Virgin Olive Oil Secoiridoids Modulate the Metabolic Activity of Dacarbazine Pre-Treated and Treatment-Naive Melanoma Cells.

Nowadays, many individuals, whether healthy or diagnosed with disease, tend to expose themselves to various easily accessible natural products in hopes of benefiting their health and well-being. Mediterranean populations have traditionally used olive oil not only in nutrition but also in cosmetics, including skincare. In this study, the phenolic profile-composed of twelve compounds altogether, including the secoiridoids oleocanthal (OCAL) and oleacein (OCEIN)-of extra virgin olive oil (EVOO) from autochthonous cultivars from Croatia was determined using 1H qNMR spectroscopy and HPLC-DAD analysis, and its biological activity was investigated in melanoma cell lines. The EVOO with the highest OCEIN content had the strongest anti-cancer activity in A375 melanoma cells and the least toxic effect on the non-cancerous keratocyte cell line (HaCaT). On the other hand, pure OCAL was shown to be more effective and safer than pure OCEIN. Post-treatment with any of the EVOO phenolic extracts (EVOO-PEs) enhanced the anti-cancer effect of the anti-cancerous drug dacarbazine (DTIC) applied in pre-treatment, while they did not compromise the viability of non-cancerous cells. The metastatic melanoma A375M cell line was almost unresponsive to the EVOO-PEs themselves, as well as to pure OCEIN and OCAL. Our results demonstrate that olive oils and/or their compounds may have a potentially beneficial effect on melanoma treatment. However, their usage can be detrimental or futile, especially in healthy cells, due to inadequately applied concentrations/combinations or the presence of resistant cells.

Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer.

The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD+) level. This enzyme catalyzes methylation of nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further metabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H2O2. Enzymatic activity of NNMT is important for the prevention of NAM-mediated inhibition of NAD+-consuming enzymes poly-adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriately high expression and activity of NNMT, commonly present in various types of cancer, has the potential to disrupt NAD+ homeostasis and cellular methylation potential. Largely overlooked, in the context of cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT's positive effect on cellular NAD+ flux by stalling liberation of NAM and reducing NAD+ synthesis in the salvage pathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD+ depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasion of a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties. All these phenomena are related to therapy resistance and worse clinical outcomes.

Medullary Thyroid Cancer - Feature Review and Update on Systemic Treatment.

Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies. MTC may be sporadic or inherited, the latter as part of the MEN 2 syndromes. Germline mutations in the RET proto-oncogene (REarranged during Transfection) are driver mutations in hereditary MTC, whereas somatic RET mutations and, less frequently, RAS mutations, have been described in tumor tissues of sporadic MTC. Genetic screening for germline mutations in RET proto-oncogene identifies gene carriers of germline mutations. That enables primary prevention (the avoidance of disease onset by total prophylactic thyroidectomy), or at least secondary prevention (early detection) of the disease. Radical surgery with complete tumor resection is still pivotal in attaining cure for MTC. Despite recent advances, the treatment of advanced, metastatic, and progressive MTC remains challenging. Metastatic MTC can have an indolent clinical course; therefore, it is necessary to assess which patient to cure and when to initiate the treatment. Multidisciplinary boards of various specialists involved in the diagnostics and therapy of the patients with MTC in highly specialized centers with a high volume of patients provide optimal patient management. Multikinase inhibitors (MKI) vandetanib and cabozantinib were approved for the treatment of progressive or symptomatic metastatic/unresectable MTC. Although these treatments have been shown to improve progression-free survival (PFS) with higher overall response rates (ORR) compared with placebo, no MKI has been shown to increase the overall survival (OS) yet, except in the subgroup of patients with RETM918T-mutations on cabozantinib therapy. As these drugs are nonselective, significant off-target toxicities may occur. Recently, next-generation small-molecule tyrosine kinase inhibitors (TKIs) have been developed. These highly selective RET-inhibitors are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. The selective RET-inhibitor selpercatinib has been very recently registered for the treatment of RET-mutated thyroid cancer.

DIFFERENTIATED THYROID CANCER IN PEDIATRIC POPULATION (≤18 YEARS): POSTOPERATIVE TREATMENT WITH RADIOACTIVE IODINE (I-131).

The aim is to present data on the treatment and follow-up in a cohort of patients with pediatric thyroid cancer who underwent total thyroidectomy and received postoperative radioactive iodine (I-131) therapy. The study was conducted in a tertiary high-volume thyroid center, in pediatric patients with differentiated thyroid cancer who were consecutively treated during the 1965-2015 period. A total of 45 patients aged ≤18 years having undergone total thyroidectomy with or without selective neck dissection were included in the study. Decision on postoperative I-131 ablation was based on tumor characteristics, postoperative thyroglobulin level, preablative whole body scintigraphy, and/or neck ultrasound. Median age at diagnosis was 15 years. The presence of cervical lymph node metastases was significantly associated with papillary thyroid cancer, larger tumor size, involvement of two thyroid lobes, and multifocal disease. The presence of distant metastases was significantly associated with larger tumor size. None of the patients died during follow-up period, and the 5-year and 10-year overall survival rates were 100%. The 5-year and 10-year progression-free survival (PFS) rates were 87% and 73%, respectively. Male gender (p=0.046), age ≤15 years (p=0.029) and tumor size >15 mm (p=0.042) were significantly associated with inferior PFS. A significant positive trend of increase in the number of newly diagnosed patients was observed over time (p=0.011). Clinical management of pediatric thyroid cancer is challenging, especially in the light of increasing incidence in this population. Male patients younger than 15 years and with tumors of more than 15 mm in size require additional caution due to lower PFS observed.

The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. METHODS: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. RESULTS: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. CONCLUSIONS: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

Current status of iodine intake in Croatia--the results of 2009 survey.

In 1996, due to persistence of mild to moderate iodine deficiency, new law on obligatory salt iodination with 25 mg of potassium iodide (KI) per kg of salt was implemented in Croatia. Along with a new law, a new program for monitoring of iodine prophylaxis was implemented. Investigations of goiter and iodine intake performed in 2002, demonstrated sufficient iodine intake in Croatia with overall median of urinary iodine concentration (UIC) for schoolchildren in Croatia of 140 microg/L. In 2002, thyroid volumes (TV) measured by ultrasound in schoolchildren from all four geographic regions of Croatia were for the first time within the normal range according to ICCIDD reference values. Nowadays, Croatia is internationally recognized as iodine sufficient country. The aim of the present study was to assess current status of iodine intake in Croatia. The investigation was carried out in 2009. A total of 386 schoolchildren aged 7-10 years from all four major geographic regions of Croatia, 103 euthyroid pregnant women and 36 women of child-bearing age from Zagreb, the capital, were included in the survey. Urinary iodine concentration (UIC) was measured in all participants. Thyroid volumes were measured by ultrasound in schoolchildren from the capital of Zagreb (N = 101) and the village of Rude (N = 56). In the time period 2002-2009, the content of KI was analyzed in 384 salt samples from Croatian salt plants and samples of imported salt. An overall median UIC for schoolchildren in Croatia was 248 microg/L. Median UIC in pregnant women was 159 microg/L, with 50% of samples below and under 150 microg/L. Median UIC in women of child-bearing age was 136 microg/L. Thyroid volumes in schoolchildren were within the normal range according to the new reference values. Mean value of KI/kg of salt in samples from Croatian salt plants was 25.5 mg/kg and 24.9 mg/kg in samples of imported salt. A total of 72/384 (18.8%) of salt samples didn't corresponded to the Croatian law on obligatory salt iodination. Presented data indicate sufficient iodine intake of the Croatian population. Current medians of UIC in schoolchildren in Croatia are significantly higher than medians measured in 2002. This indicates that other potential sources of iodine are present in Croatian diet that may contribute to overall iodine intake. Due to rising medians of UIC in schoolchildren in Croatia, it is important to conduct nutrition studies to identify potential sources of "silent prophylaxis" in order to avoid iodine excess.

Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

Radiation therapy in treatment of fibrodysplasia ossificans progressiva: a case report and review of the literature.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic disorder with diffuse extra-skeletal bone formation. The genetic mutation responsible for FOP has recently been discovered and is connected with excessive activation of bone morphogenetic protein receptor. This disease usually begins with typical ossification pattern in early childhood, causing increasing disability and making patients totally disabled by the age of 30. Ectopic ossification develops spontaneously and can be triggered by any trauma and even intramuscular injections. The symptoms of FOP are often misdiagnosed as cancer, causing unnecessary biopsies, which can precipitate further progressive heterotopic ossification. There is no effective treatment for this severe condition. Radiotherapy can be helpful in impeding ossification, although the strict evidence for that is lacking. There are only two reports in the literature referring to the use of radiotherapy in treatment of FOP. Herein, we present a 35-year-old patient successfully treated with small doses of fractionated radiotherapy in several courses. This case indicates that radiotherapy can be useful in treating patients with FOP.

Malignancy risk assessment in adenomatoid nodules and suspicious follicular lesions of the thyroid obtained by fine needle aspiration cytology.

Our aim was to assess malignancy risk in adenomatoid nodules and suspicious follicular lesions of the thyroid obtained by fine needle aspiration (FNA) cytology. Retrospective research was performed of 276 patients who underwent thyroid surgery after preoperative ultrasound-guided FNA diagnosis of either adenomatoid nodule, cellular follicular lesion, "suspicious for follicular neoplasm" or follicular neoplasm. Out of 276 patients, FNA reports showed 15 diagnoses (5%) of adenomatoid nodules, 73 (26%) cellular follicular lesions, 76 (28%) "suspicious for follicular neoplasm", and 112 diagnoses (41%) of follicular neoplasm. FNA reports were compared with pathohistological findings. In FNA reports of adenomatoid nodule (N = 15), there were seven (47%) pathohistological diagnoses (PHDs) of nodular goiter, and eight (53%) PHDs of follicular adenoma. In FNA reports of cellular follicular lesion (N = 73), there were 2 (3%) PHDs of thyroiditis, 32 (44%) PHDs of nodular goiter, 38 (52%) PHDs of follicular adenoma, and one (1%) PHD of papillary carcinoma. In FNA reports of "suspicious for follicular neoplasm" (N = 76), there was one (1%) PHD of thyroiditis, 24 (32%) PHDs of nodular goiter, 47 (62%) PHDs of follicular adenoma and four (5%) diagnoses of papillary carcinoma. In FNA reports of follicular neoplasm (N = 112), there were 25 (22%) PHDs of nodular goiter, 72 (64%) PHDs of follicular adenoma, and 15 (14%) PHDs of thyroid carcinoma. We found significant difference (p < 0.01) between investigated FNA report groups according to malignancy risk. Stratification of cytologic diagnoses of follicular thyroid lesions into different subcategories with various probabilities of malignancy allows more accurate estimation of malignancy risk and individualized patient treatment, when deciding between immediate operation and close follow-ups with repeat FNA.

[Croatian Thyroid Society guidelines for rational detection of thyroid dysfunction]. / Smjernice hrvatskog drustva za stitnjacu za racionalnu dijagnostiku poremecaja funkcije stitnjace.

Thyroid dysfunction is common in the population, especially in women, and thyroid diagnostic tests are among the most often used diagnostic procedures nowadays. Many thyroid societies developed guidelines for the detection of thyroid dysfunction. An interdisciplinary team of experts from the Croatian Thyroid Society studied guidelines of other thyroid societies and international publications, and according to our tradition and clinical practice developed guidelines for rational detection of thyroid dysfunction; hypothyroidism and hyperthyroidism. The aim of these guidelines is to recommend evidence-based and rational approach to the detection of thyroid dysfunction.

The story of the Croatian village of Rude after fifty years of compulsory salt iodination in Croatia.

The village of Rude is situated near Zagreb, the capital of Croatia in the last Alpine valley on Balkan. In the past, the village was well-known area of severe iodine deficiency disorders (IDD). In 1952', distinguished Croatian endocrinologist Professor Josip Matovinovic carried out detailed village survey. Goiter prevalence in school-age children was 85.0% (with 2.3% of cretins in the village). In 1953, the first regulation on compulsory salt iodination with 10 mg of KI/kg of salt was established in former Yugoslavia. Ten years later a dramatic decrease in goiter prevalence was recorded in all endangered areas of the country and no new cretins appeared. However, at the beginning of 1990' mild to moderate iodine deficiency still persisted in Croatia. In 1991, the village of Rude survey demonstrated goiter prevalence in school-age children of 35.0% and median of urinary iodine excretion (UIE) of 7.4 microg/dL. In 1996, the new obligatory regulation with 25 mg of KI/kg of salt was established in Croatia. The study aim was to monitor IDD status in the village after the new law on compulsory salt iodination. Measurements of UIE and thyroid volumes (Tvol) by ultrasound were performed in 7-11-y-old schoolchildren living in the village of Rude. Medians of UIE and body surface area (BSA)-adjusted Tvol in boys and girls were calculated. The study included 84 children in 1997, 132 in 2000, 72 in 2002, 85 in 2003 and 46 in 2004 for UIE measurement. Thyroid volumes were measured in 1999 (43 boys and 26 girls) and in 2005 (22 boys and 26 girls). Data were compared with the new WHO/ICCIDD reference values. Medians of UIE in schoolchildren from the village of Rude demonstrated rising values in microg/dL: 11.4 in 1997, 14.3 in 2000, 17.3 in 2002, 15.4 in 2003 and 19.0 in 2004. Significant decrease in BSA-adjusted Tvol was recorded from 1999-2005 in boys and girls from the village of Rude and in 2005 Tvol were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren. As a result of increased iodine prophylaxis, IDD no longer exist in Croatia. Monitoring of IDD status in the village of Rude after new law on compulsory salt iodination in Croatia demonstrated rising medians of UIE together with significant reduction of Tvol. In 2005, Tvol in schoolchildren from the village of Rude were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren.

[Croatian Thyroid Society guidelines for the management of patients with differentiated thyroid cancer]. / Dijagnosticke i terapijske smjernice za diferencirani karcinom stitnjace Hrvatskog drustva za stitnjacu.

With the introduction of ultrasound and fine-needle aspiration biopsy at the beginning of 1980s, dramatic changes in the clinical perception of thyroid diseases happened, especially thyroid nodules and thyroid cancer. The prevalence of thyroid nodules in the population according to ultrasound findings ranges from 20-50%, while around 5% of thyroid nodules harbour cancer. During the past decades significant increase in the incidence of thyroid cancer was recorded worldwide, mainly due to increase in the incidence of papillary thyroid cancer, probably due to improved diagnostics. Many thyroid societies developed guidelines for the management of patients with differentiated thyroid cancer. An interdisciplinary team of experts of the Croatian Thyroid Society studied guidelines of other thyroid societies and international publications, and according to our tradition and clinical practice developed the Guidelines for the Management of Patients with Differentiated Thyroid Cancer. The guidelines were published at Croatian Thyroid Society web page--www.stitnjaca.org, for open discussion and recommendations. Finally, the guidelines were accepted.

Prediction of radioactive iodine remnant ablation failure in patients with differentiated thyroid cancer: A cohort study of 740 patients.

BACKGROUND: The purpose of this study was to detect parameters that could serve as predictors of radioactive iodine (I-131) ablation failure in patients with low-risk and intermediate-risk differentiated thyroid carcinoma (DTC). METHODS: Our cohort study included 740 patients with DTC who received postoperative I-131 remnant ablation. Anthropometric, biochemical, and pathohistological parameters were analyzed and correlated with ablation outcome using multivariable logistic regression models. RESULTS: Treatment failure rates were higher in patients <53 years, with N1a classification, and lymph node capsular invasion. In patients with N1a disease, thyroglobulin (Tg) > 2.4 ng/mL predicted treatment failure with 93.8% sensitivity and 52.5% specificity, and in patients with N1b disease, Tg > 14.9 ng/mL with 77.8% sensitivity and 92.9% specificity. I-131 activity was not associated with treatment outcome. CONCLUSION: Patients < 53 years old, with higher Tg levels, N1a classification, and lymph node capsular invasion have a higher risk of ablation failure. Stimulated Tg is an excellent predictor of treatment failure in patients with N1 disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 109-115, 2017.

Bone health and adherence to vitamin D and calcium therapy in early breast cancer patients on endocrine therapy with aromatase inhibitors.

OBJECTIVES: Randomized trials involving aromatase inhibitors (AIs) in the adjuvant treatment of breast cancer patients have reported increased osteoporosis risk. Bone loss can be reduced with appropriate life style, vitamin D and calcium supplements, and with bisphosphonate therapy. The aim of this analysis was to investigate adherence to vitamin D and calcium in postmenopausal breast cancer patients receiving adjuvant non-steroidal AIs, and oncologists' adherence to the bone health guidelines. MATERIAL AND METHODS: This prospective study included 438 newly diagnosed patients and those who have already been receiving non-steroidal AIs for up to 3.5 years. Median endocrine therapy duration before recruitment in the study was 10.5 months (interquartile 4.8-26.6). RESULTS: Densitometry was performed on 142 patients (32.4%) before initiation of endocrine therapy, and on additional 38 (8.6%) patients at second study visit. Densitometry was not performed on 258 (59%) patients. Vitamin D and calcium were prescribed to 329/438 (75.1%) patients at some point during the study. Patients who took more than 80% of the prescribed dose were considered adherent. Self-reported adherence was 88.4%. Osteoporosis was diagnosed in 24 patients (5.5%) of the total study population, bearing in mind that 258/438 (59%) patients did not have densitometry. Bisphosphonates were prescribed to 54/438 (12.3%) patients, whilst only 19 (35.2%) of those had osteoporosis. CONCLUSION: In this analysis, lack of oncologists' adherence to the bone health guidelines was observed. In addition, a significant proportion of the patients did not adhere to the vitamin D and calcium.

Re-ablation I-131 activity does not predict treatment success in low- and intermediate-risk patients with differentiated thyroid carcinoma.

The aim of this study was to evaluate the efficacy of different radioactive iodine (I-131) activities used for re-ablation, to compare various combinations of treatment activities, and to identify predictors of re-ablation failure in low- and intermediate-risk differentiated thyroid carcinoma (DTC) patients. The study included 128 consecutive low- and intermediate-risk patients with DTC with ablation failure after total thyroidectomy. Patient characteristics, T status, tumor size, lymph node involvement, postoperative remnant size on whole-body scintigraphy, serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-Tg antibody (TgAb), and Tg/TSH ratio were analyzed as potential predictors of the re-ablation success. Re-ablation was successful in 113 out of 128 patients (88.3 %). Mean first I-131 activity was 2868 ± 914 MBq (77.5 ± 24.7 mCi) and mean second I-131 activity 3004 ± 699 MBq (81.2 ± 18.9 mCi). There was no association between the first, second, and cumulative activity with re-ablation treatment outcome. Treatment failure was associated with higher Tg levels prior to re-ablation (Tg2) (OR 1.16, 95 % CI 1.05-1.29, P = 0.003) and N1a status (OR 3.89, 95 % CI 1.13-13.41, P = 0.032). After excluding patients with positive-to-negative TgAb conversion, Tg2 level of 3.7 ng/mL predicted treatment failure with a sensitivity of 75.0 %, specificity of 80.5 %, and a negative predictive value of 97.1 %. Patients with positive-to-negative TgAb conversion had higher failure rates (OR 2.96, 95 % CI 0.94-9.29). Re-ablation success was high in all subgroups of patients and I-131 activity did not influence treatment outcome. Tg may serve as a good predictor of re-ablation failure. Patients with positive-to-negative TgAb conversion represent a specific group, in whom Tg level should not be used as a predictive marker of treatment outcome.

PRIMARY FIBROSARCOMA OF THE THYROID GLAND: CASE REPORT.

Due to progressive dyspnea, a male patient aged 59 underwent medical examination in 2003 in a local hospital. Neck ultrasound and fine-needle aspiration biopsy (FNAB) of a suspect lesion in the thyroid gland revealed the presence of a malignant neoplasm, i.e. mesenchymal tumor. Immunocytochemistry for epithelial membrane antigen, chromogranin A and leukocyte common antigen (CD45) was negative, while vimentin and S-100 were positive. The patient was referred to a university hospital center, where further oncologic work-up was done. Neck ultrasound revealed a tumor in the left lobe of the thyroid, with extension to the aortic arch. After repeated FNAB, cytologic diagnosis of primary thyroid fibrosarcoma was established. Due to the locally advanced and consequently inoperable disease, primary radiotherapy to the neck region (64 Gy in 32 fractions) was applied, followed by 6 cycles of chemotherapy with doxorubicin. After completion of therapy, computed tomography scan demonstrated significant regression of primary disease, but it was still not amenable to surgical treatment. Thus, the decision of the oncology board was active surveillance of the patient. During 9-year follow up, no signs of progression or activity of the disease were found.

Adjuvant thyroid remnant ablation in patients with differentiated thyroid carcinoma confined to the thyroid: a comparison of ablation success with different activities of radioiodine (I-131).

OBJECTIVE: To assess efficiency of various I-131 activities on thyroid remnant ablation in thyroid cancer patients. The significance of patients' characteristics, pathologic features and levels of Tg were analyzed. PATIENTS AND METHODS: This study included 259 consecutive differentiated thyroid cancer patients, with disease confined to the thyroid, treated with I-131 after total thyroidectomy. Patients were divided into the three groups: 80 patients receiving low [1110-1850 MBq (30-50 mCi)], 121 intermediate [2775 MBq (75 mCi)] and 58 high [3700 MBq (100 mCi)] postoperative I-131 activities. Six to eight months after the application of radioiodine, measurements of TSH, Tg, anti-Tg antibodies (in hypothyroid state) together with ultrasound exam and whole-body scintigraphy were performed. RESULTS: The ablation was significantly more effective (after the first application) in patients receiving 100 mCi of I-131-89.7% than in patients receiving lower activities (P = 0.016). There was no significant difference in ablation rate between the 30-50 mCi (77.5%) and 75 mCi (70.2%) groups. In the group receiving 30-50 mCi, patients with solitary tumors had significantly higher ablation rate (P = 0.038). In patients receiving 75 mCi ablation rates were higher among older patients (P = 0.005), with infiltration of the single lobe (P = 0.005), and with solitary tumor (P = 0.012). The rates of successful ablation after the second application of I-131 (after 12-16 months) amounted to 96, 97 and 96% in the 30-50, 75 and 100 mCi groups, respectively. The activity of I-131 and age were independent factors for thyroid ablation failure after the first application of I-131 (model of binary logistic regression). CONCLUSION: The results of remnant ablation were satisfactory with all activities applied. Although after the first application of I-131 the activity of 100 mCi is significantly more effective in thyroid ablation than the administration of 30-50 mCi and 75 mCi, the ablation rates between all the three groups are similar (almost equal) after the second application. Thus, the activity to be administered may depend on patients' characteristics and a detailed consideration of the merits and demerits of each I-131 activity.

Iodine supplementation in pregnancy.

People of all ages can be affected by iodine deficiency, however, pregnant women and children are especially at a high risk. Because of changes that occur in maternal thyroid hormone economy during pregnancy and the potential unfavorable effects of iodine deficiency on the offspring, an adequate dietary iodine intake throughout the pregnancy is highly important. Therefore, the World Health Organization, United Nations Children's Fund and International Council for the Control of Iodine Deficiency Disorders have proposed that dietary intake of iodine during pregnancy should be 200-300 microg/day to compensate for the augmented T4 requirements in pregnant women. It has been shown that in countries with a longstanding and well-established universal salt iodination program where iodine sufficiency has been reached, there is a fraction of pregnant women that still have low median urinary iodine concentration, which indicates insufficient dietary iodine. Studies performed in such countries emphasize that pregnant women should use multivitamin and/ or mineral tablets specifically prepared for the needs of pregnancy and containing iodine supplements. Only the United States of America and Canada have official recommendations concerning iodine supplementation. In other countries, no such firm decisions have yet been made by medical community and public health authorities. In Croatia, an iodine sufficient country, the situation is the same. There is a need to collect adequate data on iodine supplementation and urinary iodine during pregnancy, along with the universal salt iodination program, so that definitive conclusions can be made.

Coexistence of papillary carcinoma and Hashimoto's thyroiditis.

The aim of the study was to determine the incidence of coexistence of papillary carcinoma and Hashimoto's thyroiditis in cytologic material. Cytologic findings were collected from 10508 patients that underwent ultrasound-guided fine needle aspiration cytology (FNAC) of the thyroid. Hashimoto's thyroiditis was found in 2156 (20.5%) and papillary carcinoma in 269 (2.6%) of 10508 patients with FNAC, whereas both Hashimoto's thyroiditis and papillary carcinoma were present in 42 (0.4%) patients. Among patients with FNAC diagnosis of Hashimoto's thyroiditis, the prevalence of papillary carcinoma was 1.9%. Among patients with FNAC diagnosis of papillary carcinoma, the prevalence of Hashimoto's thyroiditis was 15.6%. There was no statistically significant association between the presence of papillary carcinoma and Hashimoto's thyroiditis in patients undergoing FNAC (p=0.0522). In conclusion, in a large series of patients, the incidence of Hashimoto's thyroiditis and papillary carcinoma coexistence in cytologic material was 0.4%. There was no statistically significant relationship between Hashimoto's thyroiditis and papillary carcinoma in cytologic material.