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Although the role of the thyroid ultrasound is well established in the initial thyroid nodule work up, it is still equivocal whether the thyroid ultrasound pattern could have an impact on refining malignancy risk after an indeterminate cytopathology result. We aim to assess the possible supportive role of the thyroid nodule ultrasound malignancy risk features listed in the Polish guidelines when a biopsy result is indeterminate.We retrospectively reviewed thyroid ultrasound scans from 175 adult patients with thyroid nodules and indeterminate cytopathology results, who underwent thyroid surgery. Sonographic malignancy risk features were reported in accordance with the guidelines of the Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma and included the following: solid structure, hypoechogenicity, microcalcifications, taller than wide shape, irregular margins, features of extrathyroidal expansion, suspicious cervical lymph nodes.The malignancy risk in relevant cytological categories, estimated on the basis of histological verification, was 10.9% for Bethesda III category, 12.1% for Bethesda IV, and 71.4% for Bethesda V. The predominant type of thyroid malignancy was papillary thyroid carcinoma (79%). Thyroid nodules sonographic malignancy risk features provided high specificity but low sensitivity in selected groups of indeterminate thyroid nodules. Microcalcifications was the only characteristic that solely had a clinically relevant positive likelihood ratio (10) to suggest malignancy in the analysed cohort, but it was not observed in thyroid nodules eventually verified as follicular thyroid carcinoma. An accumulation of more than one sonographic risk feature yielded significant increase in malignancy risk only in Bethesda V category thyroid nodules.The impact of sonographic malignancy risk features on refining post-biopsy probability of thyroid cancer in thyroid nodule with indeterminate cytopathology, may be inadequate to sort patients (without any doubt) between those who require thyroid surgery and those who only require surveillance. There is an urgent need to search for new tools in the diagnostics of indeterminate thyroid nodules and to standardize thyroid ultrasound reports.

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

Graves’ disease (GD) is the most common cause of pediatric hyperthyroidism. In children and adolescents the clinical GD course is different from this seen in adults, due to low remission rate and high prevalence of adverse events related to treatment with antithyroid drugs (ATDs). The majority of patients in this group require definitive therapy. As in adults, there are two treatment options – thyroid ablation with radioactive iodine (RAI) or surgery with preferred procedure of total thyroidectomy (TT). The choice of definitive therapy depends on many important factors such as children‘s age, effectiveness of the first- line ATD treatment, presence of ATDs side effects, presence of large goiter or thyroid nodules and concomitant diseases. The following paper provides the current guidelines on GD management in children and compares the efficacy of both definitive treatment methods as well as the acute and long-term complication rates, which must be taken into account to choose the optimal therapeutic option.

Background Renin-angiotensin system inhibitors (RASIs) are widely used in the treatment of hypertension. However, their impact on the outcome of the combined treatment of rectal cancer is poorly understood. The aim of this study was to assess the effect of RASIs on the survival of rectal cancer patients with associated hypertension after neoadjuvant treatment and radical resection. Methods Between 2008 and 2016, 242 radical (R0) rectal resections for cancer were performed after neoadjuvant treatment in patients with associated hypertension. At the time of treatment, 158 patients were on RASIs, including 35 angiotensin-receptor antagonists (ARB) users and 123 angiotensin-converting enzyme inhibitors (ACEI) users. Eighty-four patients were on drugs other than RASIs (non-RASI users). The survival analysis was performed using the Kaplan–Meier estimator with the log-rank test and the Cox proportional hazards model. Results The log-rank test showed a significantly worse overall survival (OS) in the group of ACEI users compared to ARB users (p = 0.009) and non-RASI users (p = 0.013). Disease-free survival (DFS) was better in the group of ARB users compared to ACEI users. However, the difference was not statistically significant (p = 0.064). The Multivariate Cox analysis showed a significant beneficial effect of ARBs on OS (HR: 0.326, 95% CI: 0.147–0.724, p = 0.006) and ARBs on DFS (HR: 0.339, 95% CI: 0.135–0.850, p = 0.021) compared to ACEIs. Other factors affecting OS included age (HR: 1.044, 95% CI: 1.016–1.073, p = 0.002), regional lymph node metastasis (ypN +) (HR: 2.157, 95% CI: 1.395–3.334, p = 0.001) and perineural invasion (PNI) (HR: 3.864, 95% CI: 1.799–8.301, p = 0.001). Additional factors affecting DFS included ypN + (HR: 2.310, 95% CI: 1.374–3.883, p = 0.002) and PNI (HR: 4.351, 95% CI: 1.584–11.954, p = 0.004). Conclusions The use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.

Introduction A crucial issue in the management of thyroid nodules is to estimate, as accurately as possible, the malignancy risk in thyroid lesions. The key tool for risk stratification is fine needle aspiration biopsy. Unfortunately, approximately 20 % of biopsy results are indeterminate. The malignancy risk assigned to these categories does not allow unequivocal further management. Objectives We aimed to assess the malignancy risk in indeterminate thyroid nodules in the Polish population, and to analyze the effectiveness of clinical decisions after an indeterminate cytological diagnosis in Polish clinical practice. Patients and methods The retrospective analysis included 222 indeterminate thyroid nodules in 222 patients. The ultrasound features were assessed from scans preceding a thyroid biopsy. Cytology results were classified according to the Bethesda system. The nature of the thyroid nodule was determined on the basis of a histopathological analysis or follow up. Results The analyzed cohort included 82 lesions in Bethesda category III, 75 in Bethesda category IV and 65 in Bethesda category V. The malignancy risk, estimated on the basis of histological verification and surveillance was 6.7% for Bethesda III, 11.3% for Bethesda IV and 70.3%for Bethesda V category. An ultrasound pattern was not effective enough for refining the malignancy risk after obtaining an indeterminate cytopathology result. In the case of surgery, postoperative hypoparathyroidism was significantly more frequent following more extensive surgical procedures. Conclusions Majority of Polish patients with thyroid nodules assigned to cytological categories Bethesda III and IV is overtreated using diagnostic tools currently available in Poland.

Optimal therapeutic strategy in low advanced papillary thyroid carcinoma (PTC) is still a matter of debate. The management differs depending on the country.A prospective non-randomized study was performed to evaluate whether less extensive surgery could be a safe, acceptable, and sufficient therapeutic option in PTC cT1N0M0 patients. The present paper summarizes the results of over a 5-year follow-upMaterialOur prospective group (PG) treated between 2011 and 2015 consisted of 139 patients with cT1aN0M0 PTC who underwent lobectomy (LT) as initial surgical treatment (PGcT1aN0M0 group) and 102 cT1bN0M0 patients in whom total thyroidectomy (TT) with unilateral central neck dissection (CND) was performed (PGcT1bN0M0). PG was compared with the retrospective group (RG) of patients who underwent TT with bilateral CND between 2004 and 2006: 103 cT1aN0M0 patients (RGcT1aN0M0) and 91cT1bN0M0 (RGcT1bN0M0). The risks of reoperation, cancer relapse and postoperative complications were analyzed.ResultsOnly 12 cT1aN0M0 patients (7.6%) withdrew from the trial and underwent TT with bilateral CND. Over 90% of patients accepted less extensive surgery. In 4 cT1aN0M0 cases, TT with CND was performed due to lymph node metastases found intraoperatively. The initial clinical stage according to the TNM/AJCC 7th edition was confirmed histologically in 77% of cases in PGT1aN0M0 and in 72% in PGT1bN0M0, respectively. 24 PGcT1aN0M0 patients were reoperated on. In this group, cancer lesions in the postoperative histological specimens were found in 8 cases (32%). Five-year disease-free survival (DFS) was excellent. However, no statistically significant differences were found between PG and RG groups (99.3% in PGcT1aN0M0 and 99.0%, in RGcT1aN0M0; p = 0.41 and 98%, in PGcT1bN0M0 and 94.4% in RGcT1bN0M0; p=0.19). No significant differences were observed in the incidence of early paresis of the recurrent laryngeal nerves between PG and RG. However, as predicted, LT completely eliminated the risk of postoperative hypoparathyroidism.SummaryThe results of the prospective clinical trial confirm that less extensive surgery in adequately selected low-advanced PTC patients is both safe and sufficient.

Background Regional lymph node metastases are the main adverse prognostic factor in patients with rectal cancer without distant metastases. There are discrepancies, however, regarding additional risk factors in the group of ypN + M0 patients. The purpose of the study was to assess clinical and pathological factors affecting long-term oncological outcomes in the group of ypN + M0 patients after radical rectal anterior resection. Methods 112 patients with ypN + M0 rectal cancer after neoadjuvant therapy and radical anterior resection were subject to a retrospective analysis. The effect of potential factors on survival was assessed with the use of Kaplan–Meier curves together with a log-rank test and multiple factor Cox proportional hazards model. Results In the multiple factor Cox analysis, adverse factors affecting disease-free survival (DFS) were: the use of angiotensin-converting enzyme inhibitors (ACEIs) (hazard ratio HR: 3.11, 95% CI 1.01–9.56, p = 0.047), presence of perineural invasion (HR: 7.27, 95% CI 2.74–19.3, p p = 0.001), while a positive factor was the negative lymph node (NLN) count > 7 (HR: 0.33, 95% CI 0.12–0.88, p = 0.026). In the disease-specific survival (DSS) analysis, an adverse factor was the use of ACEIs (HR: 4.275, 95% CI 1.44–12.694, p = 0.009), while a positive effect was caused by NLN > 5 (HR: 0.22, 95% CI 0.082–0.586, p = 0.002). Conclusions The use of ACEIs may have a negative effect on long-term treatment outcomes in patients with ypN + M0 rectal cancer. In this group of patients, the NLN count seems to be an important prognostic factor, as well.

[Context]: How lymph node metastasis (LNM)-associated mortality risk is affected by BRAF V600E in papillary thyroid cancer (PTC) remains undefined. [Objective]: To study whether BRAF V600E affected LNM-associated mortality in PTC. [Design, Setting, and Participants]: We retrospectively analyzed the effect of LNM on PTC-specific mortality with respect to BRAF status in 2638 patients (2015 females and 623 males) from 11 centers in 6 countries, with median age of 46 [interquartile range (IQR) 35-58] years and median follow-up time of 58 (IQR 26-107) months. [Results]: Overall, LNM showed a modest mortality risk in wild-type BRAF patients but a strong one in BRAF V600E patients. In conventional PTC (CPTC), LNM showed no increased mortality risk in wild-type BRAF patients but a robustly increased one in BRAF V600E patients; mortality rates were 2/659 (0.3%) vs 4/321 (1.2%) in non-LNM vs LNM patients (P = 0.094) with wild-type BRAF, corresponding to a hazard ratio (HR) (95% CI) of 4.37 (0.80-23.89), which remained insignificant at 3.32 (0.52-21.14) after multivariate adjustment. In BRAF V600E CPTC, morality rates were 7/515 (1.4%) vs 28/363 (7.7%) in non-LNM vs LNM patients (P < 0.001), corresponding to an HR of 4.90 (2.12-11.29) or, after multivariate adjustment, 5.76 (2.19-15.11). Adjusted mortality HR of coexisting LNM and BRAF V600E vs absence of both was 27.39 (5.15-145.80), with Kaplan-Meier analyses showing a similar synergism. [Conclusions]: LNM-associated mortality risk is sharply differentiated by the BRAF status in PTC; in CPTC, LNM showed no increased mortality risk with wild-type BRAF but a robust one with BRAF mutation. These results have strong clinical relevance., This work was supported partly by the following funding at the individual participating centers: Polish National Center of Research and Development MILESTONE Project—molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant No. STRATEGMED2/267398/4/ NCBR/2015 (Poland, AC, BJ); Grants No. PID2019-105303RB-I00 (AEI from MICINN), GCB14142311CRES (AECC Foundation), and B2017/BMD-3724 TIRONET2-CM (Spain; PS and GR-E); Grant No. AZV 16-32665A and MH CZ-DRO (Institute of Endocrinology-EU, 00023761) (Czech Republic; BB, VS); NIH/ National Institute on Aging Grant No. 5R03AG042334-02 (LY); and grants from the Qingdao Science and Technology Project for People’s Livelihood No.13-1-3-58-nsh (China; FW) and the Innovative Platform Project of Qingdao No.12-1-2-15-jch (China; YW).

Papillary thyroid carcinoma (PTC) is most common among all thyroid cancers. Multiple genomic alterations occur in PTC, and gene rearrangements are one of them. Here we screened 14 tumors for novel fusion transcripts by RNA-Seq. Two samples harboring RET/PTC1 and RET/PTC3 rearrangements were positive controls whereas the remaining ones were negative regarding the common PTC alterations. We used Sanger sequencing to validate potential fusions. We detected 2 novel potentially oncogenic transcript fusions: TG-FGFR1 and TRIM33-NTRK1. We detected 4 novel fusion transcripts of unknown significance accompanying the TRIM33-NTRK1 fusion: ZSWIM5-TP53BP2, TAF4B-WDR1, ABI2-MTA3, and ARID1B-PSMA1. Apart from confirming the presence of RET/PTC1 and RET/PTC3 in positive control samples, we also detected known oncogenic fusion transcripts in remaining samples: TFG-NTRK1, ETV6-NTRK3, MKRN1-BRAF, EML4-ALK, and novel isoform of CCDC6-RET.

Patient: Female, 51-year-old (was first diagnosed as 23-year-old) Final Diagnosis: Parathyroid carcinoma Symptoms: Hypercalcemia • hypercalcemic shock • nephrolithiasis Medication: — Clinical Procedure: Pharmacological treatment • surgery and radiotherapy Specialty: Endocrinology and Metabolic • Oncology Objective: Rare disease Background: Parathyroid carcinoma (PC), accounting for 0.005% of all cancers, is responsible for less than 1% of all cases of primary hyperparathyroidism, and equally affects males and females, usually in 4th or 5th decades of life. PC can occur sporadically and can be associated with congenital genetic syndromes such as hyperparathyroidism-jaw tumor syndrome (HPT-JT), isolated familial hyperparathyroidism, or multiple endocrine neoplasia 1 and 2 syndromes. Surgery is the main treatment, with a limited role of radio- and chemotherapy, which allows 49–77% of patients to survive 10 years. In this work we report the case of a patient with parathyroid carcinoma, whose treatment required 13 surgeries over a period of 27 years, together with radiotherapy and pharmacological treatment. Case Report: A 51-year-old woman was first diagnosed with primary hyperparathyroidism in 1993 at the age of 23. From 1993 to present, she underwent 13 surgeries and 33 courses of radiotherapy due to recurrent lesions, which initially had a character of parathyroid adenomas, then parathyromatosis, and finally were diagnosed as parathyroid carcinoma. The patient also required and currently requires complex pharmacological treatment to control the calcemia and manage the complications of the primary disease. Supervision by the multidisciplinary professional medical team allows the patient to lead a normal life with good control of the disease. Conclusions: Parathyroid carcinoma is a rare disease with a number of complications; however, obtaining satisfactory long-term survival with acceptable quality of life is achievable.

Background The main negative prognostic factors in patients with rectal cancer after radical treatment include regional lymph node involvement, lymphovascular invasion, and perineural invasion. However, some patients still develop cancer recurrence despite the absence of the above risk factors. The aim of the study was to assess clinicopathological factors influencing long-term oncologic outcomes in ypN0M0 rectal cancer patients after neoadjuvant therapy and radical anterior resection. Methods A retrospective survival analysis was performed on a group of 195 patients. We assessed clinicopathological factors which included tumor regression grade, number of lymph nodes in the specimen, Charlson comorbidity index (CCI), and colorectal anastomotic leakage (AL). Results In the univariate analysis, AL and CCI > 3 had a significant negative impact on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). After the division of ALs into early and late ALs, it was found that only patients with late ALs had a significantly worse survival. The multivariate Cox regression analysis showed that CCI > 3 was a significant adverse risk factor for DFS (HR 5.78, 95% CI 2.15–15.51, p < 0.001), DSS (HR 7.25, 95% CI 2.25–23.39, p < 0.001), and OS (HR 3.9, 95% CI 1.72–8.85, p = 0.001). Similarly, late ALs had a significant negative impact on the risk of DFS (HR 5.05, 95% CI 1.97–12.93, p < 0.001), DSS (HR 10.84, 95% CI 3.44–34.18, p < 0.001), and OS (HR 4.3, 95% CI 1.94–9.53, p < 0.001). Conclusions Late AL and CCI > 3 are the factors that may have an impact on long-term oncologic outcomes. The impact of lymph node yield on understaging was not demonstrated.

The purpose of this work was to investigate the distinct and common metabolic features of the malignant and benign thyroid lesions in reference to the non-transformed tissue from the contralateral gland (chronic thyroiditis and colloid goiter). 1H HR MAS NMR spectra of 38 malignant lesions, 32 benign lesions and 112 samples from the non-tumoral tissue (32 from chronic thyroiditis and 80 samples from colloid goiter) were subjected both to multivariate and univariate analysis. The increased succinate, glutamine, glutathione, serine/cysteine, ascorbate, lactate, taurine, threonine, glycine, phosphocholine/glycerophosphocholine and decreased lipids were found in both lesion types in comparison to either colloid goiter or chronic thyroiditis. The elevated glutamate and choline, and reduced citrate and glucose were additionally evident in these lesions in reference to goiter, while the increased myo-inositol—in comparison to thyroiditis. The malignant lesions were characterized by the higher alanine and lysine levels than colloid goiter and thyroiditis, while scyllo-inositol was uniquely increased in the benign lesions (not in cancer) in comparison to both non-tumoral tissue types. Moreover, the benign lesions presented with the unique increase of choline in reference to thyroiditis (not observed in the cancerous tissue). The metabolic heterogeneity of the non-tumoral tissue should be considered in the analysis of metabolic reprogramming in the thyroid lesions.

lt;bgt;Introduction:lt;/bgt; The complications of surgical treatment for rectal cancer, particularly anastomotic leaks after anterior resection, are a significant clinical problem. We retrospectively analysed preoperative factors that may affect the occurrence of complications.lt;brgt;lt;bgt;Meterial and Methods:lt;/bgt; A total of 392 rectal cancer patients were included in a retrospective analysis. A total of 257 anterior resections (AR) and 135 abdominoperineal resections (APR) were performed. The risk factors for early postoperative complications were analysed by logistic regression and receiver operating characteristic curves.lt;brgt;lt;bgt;Results:lt;/bgt; The significant risk factors for severe complications (grade 3B and higher on the Clavien-Dindo scale) in the multivariate analysis were neutrophil to lymphocyte ratiogt; 5 (P = 0.047) in the AR group, age of the patients (P = 0.031) in the APR group, and coronary artery disease in both groups (P = 0.03, P = 0.011, respectively). There were no risk factors for anastomotic leaks in the AR group before the analysis was divided into early and late leaks. In the univariate analysis, the statistically significant risk factors for early leaks were preoperative neutrophil to lymphocyte ratiogt; 5 and peripheral blood platelet count, while late leaks were associated with coronary artery disease; however, in the multivariate analysis, these factors were not statistically significant.lt;brgt;lt;bgt;Conclusions:lt;/bgt; The risk factors for severe postoperative complications were neutrophil to lymphocyte ratiogt; 5, advanced age of the patients and coronary artery disease. The different risk factors for early and late anastomotic leaks after anterior resection may indicate their different aetiologies.

Background One of the most severe complications of low anterior rectal resection is anastomotic leakage (AL). The creation of a loop ileostomy (LI) reduces the prevalence of AL requiring surgical intervention. However, up to one-third of temporary stomas may never be closed. The first aim of the study was to perform a retrospective assessment of the impact of LI on the risk of permanent stoma (PS) and symptomatic AL. The second aim of the study was to assess preoperative PS risk factors in patients with LI. Methods A total of 286 consecutive patients who underwent low anterior rectal resection were subjected to retrospective analysis. In 101 (35.3%) patients, diverting LI was performed due to low anastomosis, while in the remaining 185 (64.7%) patients, no ileostomy was performed. LIs were reversed after adjuvant treatment. Analyses of the effect of LI on symptomatic AL and PS were performed. Among the potential risk factors for PS, clinical factors and the values of selected peripheral blood parameters were analysed. Results PS occurred in 37.6% and 21.1% of the patients with LI and without LI, respectively (p < 0.01). Symptomatic ALs were significantly more common in patients without LI. In this group, symptomatic ALs occurred in 23.8% of patients, while in the LI group, they occurred in 5% of patients (p < 0.001). In the LI group, the only significant risk factor for PS in the multivariate analysis was preoperative plasma fibrinogen concentration (OR = 1.007, 97.5% CI 1.002–1.013, p = 0.013). Conclusions Although protective LI may reduce the incidence of symptomatic AL, it can be related to a higher risk of PS in this group of patients. The preoperative plasma fibrinogen concentration can be a risk factor for PS in LI patients and may be a useful variable in decision-making models.

Introduction: Pheochromocytomas in hereditary syndromes tend to grow multifocal with adrenal involvement on both sides. Surgical treatment with bilateral adrenalectomy inevitably leads to life-long hormonal dependence, which significantly affects quality of life. The development of minimally invasive adrenal surgery has created a chance to preserve adrenal cortex function in these patients. The aim of the present study was to evaluate the safety of laparoscopic cortical-sparing adrenal surgeries and their efficacy in the prevention of postoperative adrenal insufficiency in patients with hereditary pheochromocytomas. Material and methods: We retrospectively analysed the medical histories of 10 patients, who underwent 10 laparoscopic cortical sparing adrenal surgeries from January 2015 to January 2019 in our centre. The decision to perform sparing surgery was based on preoperative diagnosis of hereditary syndrome in line with the result of DNA analysis or its diagnosis based on the clinical appearance. All surgeries were performed laparoscopically from transperitoneal access in the lateral decubitus position, with preserving 1/3–1/4 adrenal tissue. The sufficiency of remnant adrenal tissue was assessed in all patients. The median time of follow-up was three years (ranged 0.5–4 years). Results: No intraoperative complications were observed. One case of acute heart failure was the only early postoperative adverse event. There were no late postoperative complications and no local recurrences observed. In one out of three patients undergoing sparing surgery as a second procedure after former total adrenalectomy, adrenal cortex failure occurred. In all patients after unilateral surgery or after bilateral surgery performed simultaneously (total adrenalectomy at one side and sparing surgery contralaterally), function of remnant adrenal tissue was preserved. Conclusions: In hereditary pheochromocytomas, with minimal risk of malignant process, laparoscopic cortical sparing adrenal surgeries are the safe approach and provide the chance to preserve adrenal cortex function.

Transcriptome of papillary thyroid cancer (PTC) is well characterized and correlates with some prognostic and genotypic factors, but data addressing the interaction between PTC and tumor microenvironment (TME) are scarce. Therefore, in the present study, we aimed to assess the impact of TME on gene expression profile in PTC. We evaluated the gene expression profile in PTC and normal thyroid cells isolated by laser capture microdissection and in whole tissue slides corresponding to the entire tumor. We included 26 microdissected samples for gene expression analysis (HG-U133 PLUS 2.0, Affymetrix, currently Thermo Fisher Scientific USA): 15 PTC samples, 11 samples of normal thyrocytes, and 30 whole slides (15 PTC and 15 normal thyroid). Transcripts were divided into three groups: differentially expressed both in microdissected and whole slides, transcripts differently expressed in microdissected samples and not changed in whole slides, and transcripts differentially expressed in whole slides and not changed in microdissected samples. Eleven genes were selected for validation in an independent set of samples; among them, four genes differentiated only microdissected PTC and normal cells. Two genes (PTCSC and CTGF) were confirmed. One gene (FOS) was not confirmed by the validation, whereas EGR1 was also significant in whole slide analysis. The other seven genes (TFF3, FN1, MPPED2, MET, KCNJ2, TACSTD2, and GALE) showed differentiated expression in microdissected thyrocytes and in whole tumor slides. Most of identified genes were related to the tumor-microenvironment interaction and confirmed the crosstalk between TME and cancer cells.

[Introduction]: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management., [Methods]: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months)., [Results]: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC., [Conclusions]: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC., This study was supported partly by US National Institutes of Health (NIH) Grant Nos. R01CA215142 and R01CA189224 (M.X.) and by the following additional funding at the individual participating centres: Polish National Center of Research and Development MILESTONE (Molecular Diagnostics and Imaging in Individualized Therapy for Breast, Thyroid and Prostate Cancer) Project Grant No. STRATEGMED2/267398/4/NCBR/2015 (A.C., B.J.); grants from the Menzies Health Institute, Griffith University, Queensland Cancer Council, and Queensland Smart State Fellowship in Australia (A.K.L.); Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) Grant No. SAF2016-75531-R, Instituto de Salud Carlos III Grant No. PI14/01980, Asociación Española Contra el Cáncer Foundation Grant No. GCB14142311CRES, and TIRONET2-CM Grant No. B2017/BMD-3724 TIRONET2-CM in Spain (P.S., G.R.-E.); Institute of Endocrinology Grant Nos. AZV 16-32665A and MH CZ-DRO 00023761 in the Czech Republic (B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (R.C.-B.) in Australia; National Institute on Aging, NIH, Grant No. 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute in Italy (D.V. and R.E.).

There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example. All these factors contribute to the great complexity in the development of a tumour from cancer cells. In the present review, we summarise the knowledge accumulated about the heterogeneity of TCs. Further research in this direction should help to gain a better understanding of the underlying mechanisms contributing to the development and diversity of TCs, paving the way toward more effective treatment strategies.

Medullary thyroid carcinoma (MTC) still remains a rare endocrine tumor. 20-25% of MTC cases are genetically determined. The detection of the RET proto-oncogene mutation in 1993 allowed to understand the unique genotype-phenotype relationships in hereditary medullary thyroid carcinoma (HMTC) and formed the basis for therapeutic decisions based on the molecular results. Currently, prophylactic thyroidectomy is a commonly adopted and accepted therapeutic method. The decision on the time and extent of surgery should be made based on the results of molecular examination, the assessment of calcitonin (Ct) concentration and family history. Treatment of patients with HMTC requires the cooperation of a multidisciplinary team of experts and should be done in specialized centers only. The study is a review of the current guidelines for surgical management in the MEN2 syndrome.

The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity.

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A&mdash, U133, set B&mdash, HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.

TERT promoter (TERTp) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of TERTp mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the BRAF V600E mutation. A total of 189 consecutive PTC specimens with known BRAF mutational status were evaluated. TERTp mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional TERTp alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the TERTp hotspot mutations were highly correlated with the presence of the BRAF V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of TERTp mutations being key molecular modulators responsible for PTC aggressiveness requires further studies.

[Purpose]: For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor., [Patients and Methods]: We conducted a comparative study of the relationship between patient age at diagnosis and PTC-specific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study., [Results]: There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed., [Conclusion]: The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC., Supported by National Institutes of Health (NIH) Grants No. R01CA113507 and R01CA189224 (M.X.); Polish National Center of Research and Development MILESTONE Project Grant No. STRATEGMED2/267398/4/NCBR/2015 (Poland, A.C., B.J.); grants from Menzies Health Institute, Griffith University, Queensland Cancer Council and Queensland Smart State Fellowship (Australia; A.K.L.); Grants No. SAF2013-44709-R and SAF2016-75531-R (MINECO and FEDER), RD12/0036/0030, PI14/01980 (ISCIII), and GCB14142311CRES (AECC Foundation) (Spain; P.S. and G.R-E); Grants No. AZV 16-32665A and MH CZ-DRO (Institute of Endocrinology-EU, 00023761; Czech Republic; B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (Australia; R.C.-B.); NIH/National Institute on Aging Grant No. 5R03AG042334-02 (L.Y.); and grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute (Italy; D.V., R.E.).

[Purpose]: To test whether the prognostic risk of male sex in papillary thyroid cancer (PTC) is determined by BRAF V600E and can thus be stratified by BRAF status. [Patients and Methods]: We retrospectively investigated the relationship between male sex and clinicopathologic outcomes in PTC, particularly mortality, with respect to BRAF status in 2,638 patients (male, n = 623; female, n = 2,015) from 11 centers in six countries, with median age of 46 years (interquartile range, 35-58 years) at diagnosis and median follow-up time of 58 months (interquartile range, 26-107 months). [Results]: Distant metastasis rates in men and women were not different in wild-type BRAF PTC but were different in BRAF V600E PTC: 8.9% (24 of 270) and 3.7% (30 of 817; P = .001), respectively. In wild-type BRAF PTC, mortality rates were 1.4% (five of 349) versus 0.9% (11 of 1175) in men versus women (P = .384), with a hazard ratio (HR) of 1.59 (95% CI, 0.55 to 4.57), which remained insignificant at 0.70 (95% CI, 0.23 to 2.09) after clinicopathologic multivariable adjustment. In BRAF V600E PTC, mortality rates were 6.6% (18 of 272) versus 2.9% (24 of 822) in men versus women (P = .006), with an HR of 2.43 (95% CI, 1.30 to 4.53), which remained significant at 2.74 (95% CI, 1.38 to 5.43) after multivariable adjustment. In conventional-variant PTC, male sex similarly had no effect in wild-type BRAF patients; mortality rates in BRAF V600E patients were 7.2% (16 of 221) versus 2.9% (19 of 662) in men versus women (P = .004), with an HR of 2.86 (95% CI, 1.45 to 5.67), which remained significant at 3.51 (95% CI, 1.62 to 7.63) after multivariable adjustment. [Conclusion]: Male sex is a robust independent risk factor for PTC-specific mortality in BRAF V600E patients but not in wild-type BRAF patients. The prognostic risk of male sex in PTC can thus be stratified by BRAF status in clinical application., Supported by US National Institutes of Health (NIH) Grants No. R01CA215142 and R01CA189224 (M.X.) and by the following additional funding at the individual participating centers: Polish National Center of Research and Development MILESTONE (Molecular Diagnostics and Imaging in Individualized Therapy for Breast, Thyroid and Prostate Cancer) Project Grant No. STRATEGMED2/267398/4/NCBR/2015 (A.C., B.J.); grants from the Menzies Health Institute, Griffith University, Queensland Cancer Council, and Queensland Smart State Fellowship in Australia (A.K.L.); Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) Grant No. SAF2016- 75531-R, Instituto de Salud Carlos III Grant No. PI14/01980, Asociación Española Contra el Cáncer Foundation Grant No. GCB14142311CRES, and TIRONET2-CM Grant No. B2017/BMD-3724 TIRONET2-CM in Spain (P.S., G.R.-E.); Institute of Endocrinology Grants No. AZV 16-32665A and MH CZ-DRO in the Czech Republic (B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (R.C.-B.) in Australia; National Institute on Aging, NIH, Grant No. 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute in Italy (D.V., R.E.); and Grant No. 13-1-3-58-nsh from the Qingdao Science and Technology Project for People’s Livelihood (F.W., S.Z.), Shandong Outstanding Young Scientist Award Grant No. BS2009YY030 (F.W.), Grant No. 2013 WS0266 from the Health Department of Shandong Province (S.Z., F.W.), and Grant No. 12-1-2-15-jch from the Innovative Platform Project of Qingdao (S.Z., Y.W.) in the People’s Republic of China.

Significant advances have been made in thyroid can-cer research in recent years, therefore relevant clinical guidelines need to be updated. The current Polish guidelines "Diagnostics and Treatment of Thyroid Carcinoma" have been formulated at the "Thyroid Cancer and Other Malignancies of Endocrine Glands" conference held in Wisła in November 2015 [1].

Distinguishing between follicular thyroid cancer (FTC) and follicular thyroid adenoma (FTA) constitutes a long-standing diagnostic problem resulting in equivocal histopathological diagnoses. There is therefore a need for additional molecular markers. To identify molecular differences between FTC and FTA, we analyzed the gene expression microarray data of 52 follicular neoplasms. We also performed a meta-analysis involving 14 studies employing high throughput methods (365 follicular neoplasms analyzed). Based on these two analyses, we selected 18 genes differentially expressed between FTA and FTC. We validated them by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent set of 71 follicular neoplasms from formaldehyde-fixed paraffin embedded (FFPE) tissue material. We confirmed differential expression for 7 genes (CPQ, PLVAP, TFF3, ACVRL1, ZFYVE21, FAM189A2, and CLEC3B). Finally, we created a classifier that distinguished between FTC and FTA with an accuracy of 78%, sensitivity of 76%, and specificity of 80%, based on the expression of 4 genes (CPQ, PLVAP, TFF3, ACVRL1). In our study, we have demonstrated that meta-analysis is a valuable method for selecting possible molecular markers. Based on our results, we conclude that there might exist a plausible limit of gene classifier accuracy of approximately 80%, when follicular tumors are discriminated based on formalin-fixed postoperative material.

Medullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs as a sporadic form. It is well known that RET mutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type of RET gene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of the RET gene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.

[Context]: Multifocality is often treated as a risk factor for papillary thyroid cancer (PTC), prompting aggressive treatments, but its prognostic value remains unestablished., [Objective]: To investigate the role of tumor multifocality in clinical outcomes of PTC., [Methods]: Multicenter study of the relationship between multifocality and clinical outcomes of PTC in 2638 patients (623 men and 2015 women) with median [interquartile range (IQR)] age of 46 (35 to 58) years and median (IQR) follow-up time of 58 (26 to 107) months at 11 medical centers in six countries. Surveillance, Epidemiology and End Results (SEER) data were used for validation., [Results]: Disease recurrence in multifocal and unifocal PTC was 198 of 1000 (19.8%) and 221 of 1624 (13.6%) (P < 0.001), with a hazard ratio of 1.55 [95% confidence interval (CI), 1.28 to 1.88], which became insignificant at 1.13 (95% CI, 0.93 to 1.37) on multivariate adjustment. Similar results were obtained in PTC variants: conventional PTC, follicular-variant PTC, tall-cell PTC, and papillary thyroid microcarcinoma. There was no association between multifocality and mortality in any of these PTC settings, whereas there was a strong association between classic risk factors and cancer recurrence or mortality, which remained significant after multivariate adjustment. In 1423 patients with intrathyroidal PTC, disease recurrence was 20 of 455 (4.4%) and 41 of 967 (4.2%) (P = 0.892) and mortality was 0 of 455 (0.0%) and 3 of 967 (0.3%) (P = 0.556) in multifocal and unifocal PTC, respectively. The results were reproduced in 89,680 patients with PTC in the SEER database., [Conclusions]: Tumor multifocality has no independent risk prognostic value in clinical outcomes of PTC; its indiscriminate use as an independent risk factor, prompting overtreatments of patients, should be avoided., This study was supported by U.S. National Institutes of Health (NIH) Grants R01CA113507 and R01CA189224 to M.X. Additional supports at the individual participating centers include the following: Polish National Center of Research and Development MILESTONE Project: Molecular Diagnostics and Imaging in Individualized Therapy for Breast, Thyroid, and Prostate Cancer, grant STRATEGMED2/267398/4/NCBR/2015 (Poland, A.C., B.J.); grants from Menzies Health Institute, Queensland and Queensland Smart State fellowship (Australia; A.K.L.); grants SAF2013-44709-R (MINECO and FEDER), RD12/0036/0030, PI14/01980 (ISCIII), and GCB14142311CRES (AECC Foundation) (Spain; P.S. and G.R.-E.); grant IG 9338 from the Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (Italy) and the Beadle Family Foundation (San Antonio, TX; E.P.); grants AZV 16-32665A and MH CZ-DRO (Institute of Endocrinology-EU, 00023761) (Czech Republic; B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (Australia; R.C.-B.); NIH/ National Institute on Aging grant 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute (Italy; D.V., R.E.); and the Health Department of Shandong Province, 2013 WS0266 and the Innovative Platform Project of Qingdao, 12-1-2-15-jch (China; S.Z.).

Wstep: Rak pecherzykowy tarczycy (FTC) jest nowotworem ktorego podloze molekularne jest malo zbadane. W podjetej analizie transkryptomu oceniono mozliwośc dyskryminacji raka i gruczolaka pecherzykowego tarczycy (FTA) na podstawie badan profilu ekspresji genow metodą tzw. nienadzorowaną (tzn. na podstawie dominujących źrodel zmienności). Analize te prowadzono by sprawdzic czy zlośliwośc guza jest rzeczywiście czynnikiem dominującym dla profilu ekspresji genow w nowotworach pecherzykowych. Material i metody: Podstawowy zbior guzow pecherzykowych obejmowal 52 probki (27 FTC i 25 FTA), z ktorych wyizolowano calkowity RNA i poddano badaniu na mikromacierzach HG-U133 Plus 2.0. Otrzymany zbior normalizowano za pomocą RMA i GC-RMA. Identyfikacji glownych źrodel zmienności dokonano metodą analizy glownych skladowych (PCA). Wyniki: Analize funkcji biologicznej genow przeprowadzono dla pierwszych 6 skladowych glownych. Geny skorelowane z pierwszą skladową pozwalaly wyodrebnic 2 klastry probek: jeden zlozony glownie z gruczolakow, z wysoką ekspresją miedzy innymi transkryptow tarczycowo-swoistych, drugi zaś, zawierający wiekszośc rakow, wykazywal zwiekszoną, ale heterogenną ekspresje genow związanych z odpowiedzią immunologiczną, a obnizoną ekspresje genow tarczycowych. Geny odpowiedzi immunologicznej stwierdzono wśrod transkryptow skorelowanych przebiegiem pierwszej, trzeciej i szostej glownej skladowej; w istotny sposob wplywaly one na rozroznienie miedzy FTC i FTA. Wnioski: W analizie nienadzorowanej stwierdzono, ze zlośliwośc (inwazyjnośc) nowotworu pecherzykowego moze byc jednym z glownych źrodel zmienności w transkryptomie tych guzow. Jednak, genomiczna odleglośc miedzy grupami FTC i FTA jest niewielka, a wyodrebnione w analizie nienadzorowanej klastry nakladają sie, stąd sama analiza nienadzorowana nie jest wystarczającym narzedziem do celow klasyfikacji tych guzow. (Endokrynol Pol 2013; 64 (5): 329–334)

Papillary thyroid cancer (PTC) shows familial occurrence, and some susceptibility single nucleotide polymorphisms (SNPs) have been identified in FOXE1 and near the NKX2-1 locus. The aim of our study was to analyse the association of PTC risk with SNPs in FOXE1 (rs965513, rs1867277, rs1443434) and near the NKX2-1 locus (rs944289) in a Polish population, and, in the second step, the interac-tion between SNPs and patient-related factors (age at diagnosis and gender).A total of 2243 DNA samples from PTC patients and 1160 controls were included in the study. The SNP analysis was performed with the allelic discrimination technique.There were significant associations of all SNPs with PTC (rs965513 odds ratio [OR] = 1.72, p = 8 × 10-7; rs1867277 OR = 1.59, p = 1 × 10-6; rs1443434 OR = 1.53, p = 1 × 10-5; rs944289 OR = 1.52, p = 4 × 10-5). Logistic regression analysis revealed an increased PTC risk in the interaction of rs944289 with age at diagnosis (OR = 1.01 per year, p = 6 × 10-4) and a decreased PTC risk in the interaction of male gender with the GGT FOXE1 protective haplotype (OR = 0.69, p = 0.01).the association between PTC and all analysed SNPs was confirmed. It was also shown that patient-related factors modify the predisposition to PTC by increasing the risk for rs944289 per year of age, and by enhancing the protective effect of the FOXE1 GGT haplotype in men.

et al., [Context]: Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. [Objective]: This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). [Methods]: This was a retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33-56 y) and median follow-up time of 37 months (interquartile range, 15-82 mo)., [Results]: The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P < .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC > CPTC ≫ FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66), and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07-11.11) and 14.96 (95% CI, 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old. [Conclusion]: This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC ≫ FVPTC, providing important clinical implications for specific variant-based management of PTC., This work was supported by the US National Institutes of Health (NIH) Grants No. RO1CA113507 and R01CA189224 (to M.X.). In addition, the studies at individual centers were supported as follows: National Science Centre Poland Grants No. N403 194340 and N N401 612440 to A.C. and B.J., respectively, and Milestone Grant No. 267398 to both (Poland); Grants from Queensland Government Smart State Fellowship and Griffith Health Institute to A.K.L. (Australia); Grants No. RD12/0036/0030 FIS-ISCIII, S2011/BMD-2328 TIRONET, and SAF2013-44709-R to P.So. (Spain); grants from Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (IG 9338) (Italy) and the Beadle Family Foundation (San Antonio, TX) to E.P.; Grant IGA MH CR NT 13901-4 to V.S. and B.B. (the Czech Republic); grants from the New South Wales Cancer Institute to C.J.O. and from Cancer Council of New South Wales to R.C.-B. (Australia); Italian Government-Ministero della Salute Grant No. RF-2011-02350857 to G.T. (Italy); Grant NIH/NIA 5R03AG042334-02 to L.Y. (United States); Grants from the Ministerodella Istruzione Universitaria e Ricerca Scientifica, the AssociazioneItaliana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute to D.V. and R.E (Italy); and Grant No. CB-2011-03-02 from the Korean Foundation for Cancer Research to Y.K.S. and T.Y.K. (South Korea); Research Grants 2012/02902-9 and 2013/03867-5 from The São Paulo State Research Foundation (FAPESP) to J.M.C. (G.O. is a FAPESP scholar and J.M.C. is a Brazilian Research Council investigator (Brazil); AIRC Grant No. IG 10316 to F.B. (Italy); Grant No. SHDC 12014229 from Shanghai Hospital Development Center to H.X. (China); Programa Operacional Regional do Norte (ON.2—O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the Fundo Europeu de Desenvolvimento Regional to M.S.-S. and P.So.

Gene expression profiling shows that, by gene signature, the difference between BRAF-positive and BRAF-negative PTC is so distinct that BRAF-positive cancer may be regarded as a molecular subtype of papillary thyroid cancer (PTC). Since much enthusiasm surrounds the BRAF-oncogene as a molecular prognostic factor, a central focus of our consideration is to weigh the current arguments for and against applying BRAF mutation status of the tumor in clinical practice. The frequency of BRAF mutation in PTC is high-45% on average, with values over 70-80% in some populations. This will mean that implementing BRAF mutation as a factor of poor prognosis will shift many PTC patients, considered up to now as low risk ones, to the more extensive treatment. We estimate that 31% of all PTC patients and 39% of those diagnosed with stage I-II disease will face the risk of overtreatment if the decision will be based on the BRAF-positivity of their tumors. Also, the risk of undertreatment in the young patients with BRAF-negative tumors is evaluated with 26%. We think that, as of now, the evidence-based support for such consequences is still weak. Thus, there is urgent need to look for genes or gene signatures which will be helpful in the stratification of BRAF-positive tumors to specify these with poor prognosis with higher accuracy, needed for clinical decisions. Considering this, in the review we summarize the present status of knowledge on other prognosis-related gene expression changes in papillary and follicular cancer and relate them to he tumor's biology.

Revised Guidelines of Polish National Societies Prepared on the initiative of the Polish Group for Endocrine Tumours approved in their final version between November 16th and 28th, 2015 by the Scientific Committee of the V Conference "Thyroid Cancer and other malignancies of endocrine glands" organised between November 14th and 17th, 2015 in Wisla, Poland; called by the following Societies: Polish Endocrine Society, Polish Society of Oncology, Polish Thyroid Association, Polish Society of Pathologists, Society of Polish Surgeons, Polish Society of Surgical Oncology, Polish Society of Clinical Oncology, Polish Society of Radiation Oncology, Polish Society of Nuclear Medicine, Polish Society of Paediatric Endocrinology, Polish Society of Paediatric Surgeons, Polish Society of Ultrasonography Gliwice-Wisła, 2015 DECLARATION: These recommendations are created by the group of delegates of the National Societies, which declare their willingness to participate in the preparation of the revised version of the Polish Guidelines. The members of the Working Group have been chosen from the specialists involved in medical care of patients with thyroid carcinoma. Directly before the preparation of the Polish national recommendations the American Thyroid Association (ATA) published its own guidelines together with a wide comment fulfilling evidence-based medicine (EBM) criteria. ATA Guidelines are consistent with National Comprehensive Cancer Network (NCCN) Recommendation. According to the members of the Working Group, it is necessary to adapt them to both the specific Polish epidemiological situation as well as to the rules referring to the Polish health system. Therefore, the Polish recommendations constitute a consensus of the experts' group, based on ATA information. The experts analysed previous Polish Guidelines, published in 2010, and other available data, and after discussion summed up the results in the form of these guidelines. It should be added that Part II, which constitutes a pathological part, has been available at the website of the Polish Society of Pathologists for acceptance of the members of the Society, and no essential comments have been proposed. The Members of the Group decided that a subgroup elected from among them would update the Guidelines, according to EBM rules, every year. The Revised Guidelines should help physicians to make reasonable choices in their daily practice; however, the final decision concerning an individual patient should be made by the caring physician responsible for treatment, or optimally by a therapeutic tumour board together with the patient, and should take into consideration the patient's health condition. It should be emphasised that the recommendations may not constitute a strict standard of clinical management imposed on medical staff. The data from clinical trials concerning numerous clinical situations are scarce. In such moments the opinion of the management may differ from the recommendations after considering possible benefits and disadvantages for the patient.

Background The molecular mechanisms driving the papillary thyroid carcinoma (PTC) are still poorly understood. The most frequent genetic alteration in PTC is the BRAFV600E mutation–its impact may extend even beyond PTC genomic profile and influence the tumor characteristics and even clinical behavior. Methods In order to identify BRAF-dependent signature of early carcinogenesis in PTC, a transgenic mouse model with BRAFV600E-induced PTC was developed. Mice thyroid samples were used in microarray analysis and the data were referred to a human thyroid dataset. Results Most of BRAF(+) mice developed malignant lesions. Nevertheless, 16% of BRAF(+) mice displayed only benign hyperplastic lesions or apparently asymptomatic thyroids. After comparison of non-malignant BRAF(+) thyroids to BRAF(−) ones, we selected 862 significantly deregulated genes. When the mouse BRAF-dependent signature was transposed to the human HG-U133A microarray, we identified 532 genes, potentially indicating the BRAF signature (representing early changes, not related to developed malignant tumor). Comparing BRAF(+) PTCs to healthy human thyroids, PTCs without BRAF and RET alterations and RET(+), RAS(+) PTCs, 18 of these 532 genes displayed significantly deregulated expression in all subgroups. All 18 genes, among them 7 novel and previously not reported, were validated as BRAFV600E-specific in the dataset of independent PTC samples, made available by The Cancer Genome Atlas Project. Conclusion The study identified 7 BRAF-induced genes that are specific for BRAF V600E-driven PTC and not previously reported as related to BRAF mutation or thyroid carcinoma: MMD, ITPR3, AACS, LAD1, PVRL3, ALDH3B1, and RASA1. The full signature of BRAF-related 532 genes may encompass other BRAF-related important transcripts and require further study.

Somatic RET mutations are detectable in two-thirds of sporadic cases of medullary thyroid cancer (MTC). Recent studies reported a high proportion of RAS somatic mutations in RET negative tumours, which may indicate RAS mutation as a possible alternative genetic event in sporadic MTC tumorigenesis. Thus, the aim of the study was to evaluate the frequency of somatic RAS mutations in sporadic medullary thyroid cancer in the Polish population and to relate the obtained data to the presence of somatic RET mutations.Somatic mutations (RET, RAS genes) were evaluated in 78 snap-frozen MTC samples (57 sporadic and 21 hereditary) by direct sequencing. Next, three randomly selected RET-negative MTC samples were analysed by the next generation sequencing.RAS mutation was detected in 26.5% of 49 sporadic MTC tumours. None of all the analysed samples showed N-RAS mutation. When only RET-negative samples were considered, the prevalence of RAS mutation was 68.7%, compared to 6% observed in RET-positive samples. Most of these mutations were located in H-RAS codon 61 (72%). None of 21 hereditary MTC samples showed any RAS mutations.RAS mutations constitute a frequent molecular event in RET-negative sporadic medullary thyroid carcinoma in Polish patients. However, their role in MTC tumorigenesis remains unclear.

et al., [Purpose]: To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). [Patients and Methods]: This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). [Results]: The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation–positive and 11.6% (125 of 1,082) of BRAF V600E mutation–negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation–positive versus –negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation–positive versus –negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. [Conclusion]: This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories., Supported by National Institutes of Health (NIH) Grants No. R01CA134225 and RO1CA113507 (M.X.); by Grant No. UL1 RR 025005 from the National Center for Advancing Translational Sciences of NIH and NIH Roadmap for Medical Research (K.A.C.); and by the following funding to individual study centers: National Science Centre Poland Grants No. N N403 194340 (A.C.) and N N401 612440 (B.J.); grants from Griffith Health Institute (Australia; A.K.L.); Grants No. BFU2010-16025, RD06/0020/0060-RD12/0036/0030 FIS, ISCIII, and S2011/BMD-2328 TIRONET (Spain; P.S.); NIH Grant No. RO1-CA50706 and the Byrne Foundation (J.A.F.); Grant No. IG 9338 from the Fondazione Cassa di Risparmio di Perugia and Associazione Italiana per la Ricerca sul Cancro (Italy) and the Beadle Family Foundation (San Antonio, TX; E.P.); Grant No. IGA MH CR NT 13901- 4 (Czech Republic; B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (Australia; R.C.- B.); Grant No. MIUR 20074zw8la from the Ministero della Istruzione Universitaria e Ricerca Scientifica and the Associazione Italiana per la Ricerca sul Cancro (Italy; G.T.); NIH/National Institute on Aging Grant No. 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute (Italy; D.V., R.E.); and Grant No. CB-2011-03-02 from the Korean Foundation for Cancer Research (South Korea; Y.K.S., T.Y.K.).

Genetic alterations involving the mitogen-activated protein kinase (MAPK) pathway are frequently demonstrated in papillary thyroid cancer (PTC). BRAF(V600E), the most frequent mutation in adult patients, is present in approximately 50% of PTC. Most clinical studies have demonstrated an association of BRAF(V600E) mutation with aggressive clinicopathological characteristics and high tumour recurrence, although the results are controversial. In this study we present the preliminary results of BRAF mutation frequence in a group of 88 Polish patients with papillary thyroid cancer (PTC) and relate it to the outcome all DTC patients operated in 2004 and 2005. BRAF (V600E) mutation was diagnosed in 38 (43%) of cases.The presence of BRAF mutation was evaluated in 88 PTC tumours. DNA was isolated from tissue parafin blocks, and the mutation V600E was evaluated by sequence analysis with an AbiPrism 377 and 3130 xl genetic analyzer (Life Technologies). Statistical analysis was carried out with the use of SPSS 12 software. The chi² and Kaplan-Meyer survival analysis were performed.From all analyzed clinico-pathological factors, only older age positively correlated with BRAF mutation frequency (p = 0.0017). Lymph node/distant metastases, multifocality, and extra-thyroid extension did not correlate with BRAF status. One cancer related death and two reccurences were observed in the BRAF+ group while one relapse was diagnosed in the BRAF- group.Although many studies document BRAF mutation as a prognostic factor in PTC our results underline that it is too early to consider it as a routine clinical predictive factor.

The aim of the study was to compare the advancement of thyroid cancer at diagnosis in Polish patients from the Silesian district in the years 1999 and 2008.The analyzed group consisted of Silesian district patients with thyroid cancer, who were registered by the Department of Tumour Epidemiology of the Institute of Oncology in Gliwice in the years 1999 and 2008. From a group of 186 patients who entered on record in 1999, 167 were qualified for this analysis. Similarly, from 238 patients registered in 2008, finally 226 were added. We analyzed: sex, age at diagnosis, histotype of thyroid cancer, and DTC staging according to TNM (UICC 2002). In 1999 there were 137 females (82.04 %) and 30 males (17.93%) with thyroid cancer diagnosed at ages 5-81 years. In 2008 there were 183 females (80.97%) and 43 males (19.03%) diagnosed at ages 14-80 years. In both groups, in 1999 and 2008, the median age was the same (51 years).In the year 1999, 119 (71%) and in 2008, 197 (87%) patients were diagnosed with papillary thyroid cancer (p = 0.0003). Relations between age and sex were similar in these years. There was some increase in frequency of patients diagnosed with papillary microcancer (pT1a), which was on the border of statistical significance (p = 0.05). A statistically significant increase of pT1 (p = 0.02) and decrease of pT4 (p = 0.001) and of pTx (p = 0.002) was observed in the year 2008 in the whole cohort of DTC patients.1. In 2008 the contribution of papillary histotype to all thyroid cancer patients (87%) was significantly higher than in 1999. 2. The percentage of DTC patients diagnosed with pT1 disease was significantly higher in 2008.

Introduction The risk of over-treatment in low-advanced PTC stages has prompted clinicians to search for new reliable prognostic factors. The presence of BRAF mutation, the most frequent molecular event in PTC, seems to be a good candidate. However, there is still lack of randomised trials and its significance has been proved by retrospective analyses, involving a large group of patients. The question arises whether this factor is useful in smaller populations, characterised for specialised centres. Thus, the aim of the study was to evaluate the use of BRAF mutation as a potential predictive marker in PTC patients. Material 233 PTC subjects treated between 2004-2006, were retrospectively analysed. Stage pT1 was diagnosed in 64.8% patients and lymph node metastases in 30.9%. Median follow-up was 7.5 years. BRAFV600E mutation was assessed postoperatively in all cases. Results BRAF V600E mutation was found in 54.5%. It was more frequent in patients > 45 years (p=0.0001), and associated with larger tumour size (p=0.004). Patients with tumours

Transient and persistent hypoparathyroidism (HPT) belong to the well known complications of total thyroidectomy performed because of thyroid carcinoma. The true frequency of persistent hypoparathyroidism is often higher than estimated in the reports published by the specialized centers with low rate of complications.Investigation whether the repeated check-up, performed over 2 years post thyroidectomy, reveals some cases of recovery in patients diagnosed with persistent HPT post thyroid cancer surgery.In total, 115 patients were included into the study, all of them treated with vitamin D derivatives and calcium supplementation. In 17 of them a diagnosis of transient hypoparathyroidism was made on the basis of evaluation performed 6 months after surgery, the remaining 98 were diagnosed with persistent HPT. Parathyroid (PTH) function was reevaluated after withdrawal of active vitamin D derivatives for 10 days and of calcium carbonate for two days during the hospital stay in patients admitted for radioiodine scan, thus after thyroxine withdrawal. The control group consisted of 123 DTC (differentiated thyroid carcinoma) patients without parathyroid dysfunction. On the basis of intact PTH serum level and calcium and phosphorus estimations HPT was unequivocally confirmed in 49 patients (50%). The remaining 49 patients exhibited normal PTH level and in 43 (86%) of them Ca(2+) level was also within normal range, thus delayed, recovery from HPT was stated.Our results indicate that reevaluation of hypoparathyroidism post total thyreoidectomy is necessary, as delayed recover of parathyroid dysfunction is a frequent phenomenon. We also propose criteria of reevaluation of HTP in patients on chronic substitutive therapy.

The studies of papillary thyroid cancer (PTC) gene expression profile have shown changes in expression of genes involved in transport of several ions. The aim of our study was a real-time PCR evaluation of three of them: KCNJ2, SLC4A4 and SLC34A2.The analysis was carried out in PTC tumors and normal thyroid samples gained from 38 patients. Real-time quantitative PCR (Q-PCR) was performed (Taqman) with beta-glucuronidase (GUS) as the reference gene.We observed 20 x increase of SLC34A2 expression in PTC. This gene encodes Na+/PO(4) (3-) cotransporter. Considerable increase of gene expression has been shown also for KCNJ2, encoding a potassium ion channel. SLC4A4, which encodes the Na+/HCO(3) (2-) cotransporter, exhibited a 7-fold decrease in PTC.The performed study revealed that SLC34A2 gene exhibited the most distinct change in expression and may become a molecular marker of papillary thyroid cancer.

Evaluation of the therapeutic benefits in relation to the stage of thyroid cancer and to the extent of surgery and the risk of postoperative complications.Retrospective analysis of differentiated thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of them were treated or diagnosed in Institute of Oncology in Gliwice between 1986-1998. Previously they were operated in various surgical centers all-over Poland. The risk of death, local relapse and postoperative complications were analyzed using the decisiontree model to evaluate the therapeutic benefits.The recurrent laryngeal nerve injury (transient or permanent) was observed in retrospective analysis in 21% of patients, while postoperative hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in patients treated by less than total thyroidectomy). The advantage of radical surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in patients treated by total thyroidectomy and 0.69 in those who received less extensive operation.The analysis of therapeutic benefits confirmed the limit of 1 cm tumor diameter between less extensive surgery and total thyroidectomy. It showed that total thyroidectomy brings a significant therapeutic benefits in patients inT1M0 stage. The improvement of overall survival and decrease of local relapse far outweigh the disadvantages related to postoperative complications.

The low incidence of relapse in differentiated thyroid carcinoma (DTC), primarily treated by total thyroidectomy and (131)I ablation, stimulates the search for optimal follow-up algorithms which do not include too many tests but are not connected with a risk of missing early recurrence. The aim of the study was to analyze the impact of the routine follow up examinations for early detection of DTC recurrence in low risk DTC patients.The group consisted of 617 DTC patients diagnosed in 1995-1996. In 513 (83%) total thyroidectomy was performed. 449 (73%) received ablative (131)I therapy. After primary approach complete remission (CR) was stated in 453 (73%), persistent disease in 116 (19%), asymptomatic hyperthyroglobulinaemia in 14 (2%). Patients with CR constituted the low risk group analyzed in this study. The median follow up was 4.16 yrs.Recurrent disease appeared in 28 (6%) patients (23 locoregional, 9 distant metastases, both in 4). Serum Tg (thyroglobulin) level at the moment of relapse diagnosis was detectable in 44% while neck sonography was the first examination to detect recurrence in 56% of cases.In the selected group of DTC patients treated by radical primary approach and showing a low risk of recurrence only half of all relapse cases are diagnosed by the rise of serum Tg level. Regular sonography contributes to the second half of diagnoses. Thus, a special weight should be put on neck sonography as the important element of regular follow up in low risk DTC patients.

In differentiated thyroid cancer (DTC) the differentiation between reactive and metastatic lymph nodes is difficult at the early stages of metastasis. The aim of the study was to assess the results of fine needle aspiration (FNA) samples examination by the use of RT-PCR for Tg mRNA. The special attention was directed to the evaluation of specificity of TgRNA estimation.The group consisted of 193 DTC patients with suspicion of lymph node recurrence and at least one positive RT-PCR result. Thyroglobulin RT-PCR was conducted in residual material left after preparation of cytological smears from FNA specimens. Primer spanning exons 3-5 were used with 39 cycles of PCR. RNA isolation control and cDNA amplification were carried out using GAPDH starters. 308 lymph node biopsies were included.246 positive results for Tg RNA were observed in the analyzed group, 71.1% confirmed by FNA. Among other 71 results, in which cytological examination did not correspond unequivocally to molecular findings, in 34 metastases were confirmed both by cytological and clinical examination. There were 11 patients operated due to the positive serial molecular examination only. In 10 (91%) of them DTC metastases were confirmed. So, the positive predictive value of the molecular result ranged between 75-89% and the negative one was 100%.In DTC patients RT-PCR Tg mRNA is helpful in qualification of suspicious lymph nodes to surgery in DTC patients. At the negative cytological finding, the positive molecular result constitutes an indication for early surgery.

To analyze the impact of time and extent of operation on overall and disease-free survival in patients with differentiated thyroid carcinoma (DTC).Retrospective analysis of 1235 DTC patients, a representative probe of patients diagnosed or treated between 1986 to 1998 was performed. 277 patients were staged T1M0 and 958 ones stagedT1M0. 10-year outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard model.The T1M0 patients were characterized by the best overall and disease-free survival independently of the time and the extent of operation (98% and 96% respectively); inT1M0 group the survival was better in patients who were treated by total thyroidectomy (94% and 68% respectively) than in patients treated by non-total thyroidectomy (78% and 47% respectively). In patients treated by completion of total thyroidectomy delayed more than 1 year post cancer diagnosis the incidence of carcinoma in postoperative pathological material was twice as high in comparison to the group in whom total thyroidectomy was performed within the first year of therapy (p = 0.000).1. In differentiated thyroid carcinoma the prognosis is related to the extent of operation only in patients staged more than T1M0. 2. A delay12 months in completion surgery in patients with differentiated thyroid cancer (tumors1 cm of diameter) significantly increases the risk of progression of multifocal disease in thyroid remnants.

The optimal surgical treatment of children with differentiated thyroid cancer remains an important point of discussion. Especially the need for completion operation is questioned in young patients. Our objective was to examine the rate of residual neoplastic disease after non radical initial operation.From the 235 children diagnosed with differentiated thyroid cancer, 131 (56%) needed completion operation due to incomplete primary surgery. Completion operation involved thyroid bed, lymph nodes or both respectively in 91 (39%), 13 (6%) and 27 (11%) cases. Risk factors responsible for residual disease were evaluated by means of logistic regression analysis.Residual disease was detected in 46 (35%) of reoperated children (25% in thyroid bed and 85% in lymph node of lateral neck compartment). Sex and age did not influence the risk of residual disease in thyroid bed or lymph nodes. Papillary type of cancer and multifocality increased risk of residual disease in thyroid bed respectively by the factor of 15 (95% CI: 2-125) and 2.3 (95% CI: 1.2-4.4). Infiltration of thyroid capsule did not correlate with the risk of residual disease. Lymph node metastases in primary operation increased risk of residual disease by the factor of 16 (95% CI: 1.2-245). Histopathology, multifocality of primary tumour or infiltration of lymph node capsule did not influence the risk of residual disease in lymph nodes of lateral neck compartment.In children with differentiated thyroid cancer residual disease is diagnosed in about 1/3 of non radically operated cases. This high incidence justifies completion operations. The risk of residual disease is significantly increased in papillary thyroid cancer, multifocal tumours and cases with lymph node metastases.

The aim of the study was to analyze the clinical course and therapy in patients with differentiated thyroid carcinoma (DTC) diagnosed in Poland within the year 1995. The group of 478 patients with thyroid cancer (57.7% of all thyroid cancer cases diagnosed this year in Poland) was analyzed. Patients were diagnosed or treated in Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch. Detailed analysis was performed in 352 patients with DTC who were treated by surgery. 292 patients (60%) received adjuvant radioiodine therapy. Hormonal (L-thyroxine) treatment was administered to all patients. In 37 patients (8.6%) local recurrence was observed. 10-year overall survival was 96.4% and disease-free survival was respectively 68%. The comparison of Polish data to analysis in German population published by Holtzer et al. (Cancer, 2000) was also performed in this study. We conclude that DTC therapy, currently recommended in our country, gives satisfactory results and that clinical outcome and therapeutic methods are similar both in Poland and Germany.

In our study we present chosen elements of microarray analysis of gene expression profile in papillary thyroid cancer. The study group included 16 papillary thyroid cancer tissues and 16 corresponding normal tissues. Samples were analyzed on high density oligonucleotide microarrays (GeneChip HG-U133A) which contain 22.000 genes. 110 genes, which had significant changed expression, were selected by MAS 5.0 program. 3 genes were chosen to the deeper analysis: dipeptidylpeptidase 4 (DPP4), fibronectin 1 (FN1), tissue inhibitor of metalloproteinase 1 (TIMP1). DPP4-RNA were absent in normal tissue while in cancer tissue it was detected in large amount. FN1 and TIMP1 expression were detected in normal tissue but markedly increased in papillary thyroid cancer. Among these 3 genes DPP4 seems to be the best molecular marker for papillary thyroid cancer.