Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Epidemiology and Long-Term Outcomes in a Strictly Defined Cohort.

Background: A subset of encapsulated/circumscribed follicular variant of papillary thyroid carcinoma (FVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reduce overtreatment of a low-risk tumor. Study objectives were to describe the epidemiology and long-term outcomes of NIFTP in a high-volume, urban, tertiary referral center. Methods: Among patients enrolled in the Boston Medical Center (BMC) Thyroid Cancer Registry, 110 cases of FVPTC underwent index thyroid surgery at BMC between 2000 and 2016. Historically, BMC pathologists assess all malignant nodules using sections ≤0.3 cm with evaluation of the entire nodule and capsule. After review of pathology reports to identify potential NIFTPs, slides were rereviewed using criteria established by the NIFTP Working Group in 2016 and 2018. We evaluated interobserver reliability using Cohen's Kappa coefficient. Results: Among 110 FVPTCs, 15 (13%) met NIFTP criteria; 11 women and 4 men, age range 31-64 (mean 47.5) years. Mean tumor diameter was 1.7 cm (compared with 2.2 cm for FVPTC). Among NIFTP cases, there were no lymph node metastases, distant metastases, or tumor recurrences. All NIFTP cases were American Thyroid Association (ATA) low risk compared with only 68% of FVPTC (p = 0.011). Among FVPTCs, 14% had positive lymph nodes at index operation. Four patients (4%) had distant metastases. Mean follow-up time was 46 and 69 months for FVPTC and NIFTP, respectively. Among FVPTCs with an excellent response to therapy (2015 ATA guidelines), there were no recurrences. Just over half (n = 8) of patients with NIFTP received postoperative radioactive iodine (RAI) therapy. Concordance between pathologists was high for ruling out NIFTP (75%), but only 36% for ruling in NIFTP. Overall, for NIFTP designation, Cohen's Kappa was 0.39, which is considered fair. Conclusions: Although this is a relatively small cohort, all NIFTP specimens underwent updated pathology review consistent with current guidelines; mean follow-up was nearly 6 years. NIFTP represents a small fraction of the total papillary neoplasia diagnosed at this tertiary referral center (2.3%). None of the NIFTP cohort experienced an adverse oncologic event, and there were no regional or distant metastases. Over 50% of patients with NIFTP received RAI. Thus, the NIFTP reclassification may substantially reduce the number of patients who require adjuvant therapies, such as completion surgery or RAI.

Randomised comparison of 1.1 GBq and 3.7 GBq radioiodine to ablate the thyroid in the treatment of low-risk thyroid cancer: a 13-year follow-up.

Purpose: The optimal activity of radioiodine (I-131) administered for ablation therapy in papillary and follicular thyroid cancer after thyroidectomy remains unknown in a long-term (> 10 year) follow-up. Some, shorter follow-up studies suggest that activities 1.1 GBq and 3.7 GBq are equally effective. We evaluated the long-term outcomes after radioiodine treatment to extend current knowledge about the optimal ablative dose of I-131.Methods: One hundred and sixty consecutive adult patients (129 females, 31 males; mean age 46 ± 14 y, range 18-89 y) diagnosed with histologically confirmed differentiated thyroid cancer, were randomised in a prospective, phase III, open-label, single-centre study, to receive either 1.1 GBq or 3.7 GBq of I-131 after thyroidectomy. At randomisation, patients were stratified according to the histologically verified cervical lymph node status and were prepared for ablation using thyroid hormone withdrawal. No uptake in the whole-body scan with I-131 and serum thyroglobulin concentration less than 1 ng/mL at 4-8 months after treatment was considered successful ablation.Results: Median follow-up time was 13.0 years (mean 11.0 ± 4.8 y; range 0.3-17.1 y). Altogether 81 patients received 1.1 GBq with successful ablation in 45 (56%) patients. In the original study, thirty-six patients (44%) needed one or more extra administrations to replete the ablation. Of these, 4 (8.9%) and 5 (14%) patients relapsed during the follow-up, respectively. Of the 79 patients treated with 3.7 GBq 45 (57%) had successful ablation after one administration of radioiodine and 34 (43%) needed several treatments. Of these, 2 (4.4%) and 9 (26.5%) patients relapsed, respectively. The groups did not differ in the proportion of patients relapsing (p = .591).Conclusion: During follow-up of median 13 years, 3.7 GBq is not superior to 1.1 GBq in the radioiodine treatment after thyroidectomy in papillary and follicular thyroid cancer.

TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma.

BACKGROUND: TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer. PATIENTS: Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes. RESULTS: The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients. CONCLUSION: Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.

NIFT-P: Are they indolent tumors? Results of a multi-institutional study.

BACKGROUND: Encapsulated follicular variant of papillary thyroid carcinoma has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the basis of its highly indolent behavior, as proposed by an international group of experienced thyroid pathologists. METHODS: All patients from 9 high-volume endocrine surgery departments who underwent surgery between 2005 and 2015 and whose final surgical pathology revealed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (>10 mm) were included in this study. The primary outcome was to determine the potential for recurrent disease in these patients. RESULTS: Among the 363 patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features, 76% were female with a median age of 50 years (5-86 years); 345 patients (95%) underwent total thyroidectomy. A total of 65 patients had an associated micropapillary thyroid carcinoma. In the group of 133 patients who underwent prophylactic lymph node dissection (37%), 1 patient had a micrometastasis but with an associated micropapillary thyroid carcinoma. Over a median follow-up period of 5 years, 1 patient with an associated micropapillary thyroid carcinoma had recurrent disease at 6 years. All patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features without micropapillary thyroid carcinoma had no lymph node metastasis or recurrent disease. CONCLUSION: We found that noninvasive follicular thyroid neoplasm with papillary-like nuclear features presents with indolent behavior. However, the identification of an associated micropapillary thyroid carcinoma should be carefully evaluated because it could be a factor for lymph node metastasis and/or of recurrence.

Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial.

BACKGROUND: Two large randomised trials of patients with well-differentiated thyroid cancer reported in 2012 (HiLo and ESTIMABL1) found similar post-ablation success rates at 6-9 months between a low administered radioactive iodine (131I) dose (1·1 GBq) and the standard high dose (3·7 GBq). However, recurrence rates following radioactive iodine ablation have previously only been reported in observational studies, and recently in ESTIMABL1. We aimed to compare recurrence rates between radioactive iodine doses in HiLo. METHODS: HiLo was a non-inferiority, parallel, open-label, randomised controlled factorial trial done at 29 centres in the UK. Eligible patients were aged 16-80 years with histological confirmation of differentiated thyroid cancer requiring radioactive iodine ablation (performance status 0-2, tumour stage T1-T3 with the possibility of lymph-node involvement but no distant metastasis and no microscopic residual disease, and one-stage or two-stage total thyroidectomy). Patients were randomly assigned (1:1:1:1) to 1·1 GBq or 3·7 GBq ablation, each prepared with either recombinant human thyroid-stimulating hormone (rhTSH) or thyroid hormone withdrawal. Patients were followed up at annual clinic visits. Recurrences were diagnosed at each hospital with a combination of established methods according to national standards. We used Kaplan-Meier curves and hazard ratios (HRs) for time to first recurrence, which was a pre-planned secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT00415233. RESULTS: Between Jan 16, 2007, and July 1, 2010, 438 patients were randomly assigned. At the end of the follow-up period in Dec 31, 2017, median follow-up was 6·5 years (IQR 4·5-7·6) in 434 patients (217 in the low-dose group and 217 in the high-dose group). Confirmed recurrences were seen in 21 patients: 11 who had 1·1 GBq ablation and ten who had 3·7 GBq ablation. Four of these (two in each group) were considered to be persistent disease. Cumulative recurrence rates were similar between low-dose and high-dose radioactive iodine groups (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 5·9% vs 7·3%; HR 1·10 [95% CI 0·47-2·59]; p=0·83). No material difference in risk was seen for T3 or N1 disease. Recurrence rates were also similar among patients who were prepared for ablation with rhTSH and those prepared with thyroid hormone withdrawal (3 years, 1·5% vs 2·1%; 5 years, 2·1% vs 2·7%; and 7 years, 8·3% vs 5·0%; HR 1·62 [95% CI 0·67-3·91]; p=0·28). Data on adverse events were not collected during follow-up. INTERPRETATION: The recurrence rate among patients who had 1·1 GBq radioactive iodine ablation was not higher than that for 3·7 GBq, consistent with data from large, recent observational studies. These findings provide further evidence in favour of using low-dose radioactive iodine for treatment of patients with low-risk differentiated thyroid cancer. Our data also indicate that recurrence risk was not affected by use of rhTSH. FUNDING: Cancer Research UK.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features reclassification and its impact on thyroid malignancy rate and treatment.

BACKGROUND: The reclassification of noninvasive encapsulated follicular variant papillary thyroid carcinoma (FVPTC) to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) may have significant implications by changing overall malignancy rates and minimizing the extent of surgical treatment. METHODS: A retrospective review of 847 patients who underwent thyroidectomy at a single institution from January 2010 to April 2016 was performed. The subgroup with FVPTC (n = 181) was re-reviewed by endocrine pathologists for reclassification to NIFTP. The overall rate of malignancy (ROM) and within each Bethesda classification was determined before and after the reclassification of NIFTP. The extent of thyroidectomy among others in patients reclassified as NIFTP was further reviewed. RESULTS: Of 847 patients who underwent thyroidectomy, there was an overall ROM of 58% (n = 495), the majority being papillary thyroid cancer (PTC) (n = 454, 92%). In 181 patients with FVPTC, 146 underwent pathology re-review. There were 32 cases (22%) reclassified as NIFTP, reducing the overall ROM to 55%. ROM decreased across Bethesda categories I to V by the following: 3% Bethesda I, 8% Bethesda II, 8% Bethesda III, 10% Bethesda IV, and 3% Bethesda V. Among NIFTP patients, 16 underwent total thyroidectomy and 16 underwent thyroid lobectomy, of which 12 had completion thyroidectomies (75%). Twenty patients (63%) underwent central neck dissection, and nine underwent postoperative radioactive iodine ablation treatment (28%). CONCLUSIONS: A significant proportion of patients with FVPTC reclassified as NIFTP may decrease the overall institutional thyroid ROM. On final pathology, NIFTP should be regarded as an indolent tumor requiring no further surgical treatment.

[Recovery rate in differentiated thyroid cancer. Experiences of one of the Hungarian clinical centers]. / A differenciált pajzsmirigyrákban szenvedo betegek gyógyulási esélyei. Egy hazai centrum tapasztalatai.

INTRODUCTION AND AIM: The worldwide incidence of differentiated thyroid cancer (DTC) has markedly increased during the last few decades. According to the international guidelines, principles of DTC management are in transformation. The aim of our work was to evaluate patients' current likelihood of recovery. METHOD: Data of 380 patients treated between 1/Jan/2005 and 1/May/2016 at the PTE KK Ist Department of Internal Medicine were retrospectively analyzed. Female/male ratio was 306/74. Median age at diagnosis was 46 years (13-86 years), while median follow-up time was 55 months (0-144 months). Response to therapy was evaluable in 337 patients. Statistical analysis was done using SPSS (version 22.0). RESULTS: Based on the prevalence of papillary (PTC) and follicular (FTC) carcinomas (79/21%), moderate iodine deficiency has to be considered in this region. PTC patients were significantly younger and were diagnosed in earlier tumor stage. The ratio of lymph node and distant metastases was 35%/4% in PTC and 15%/14% in FTC. Radioiodine treatment was performed in a total of 542 times. 264 patients with PTC were followed up. 59% of patients were tumor-free, in 20% uncertain response, in 7% incomplete biochemical response, in 14% incomplete structural response were diagnosed and 6 patients died. Patients with FTC (n = 73) were tumor-free in 59%, uncertain response was found in 10%, incomplete structural response was diagnosed in 31%, while 10% of the patients died. CONCLUSIONS: In summary, although DTC has a favorable prognosis, in 31% of FTC patients and in 14% of PTC patients, tumor-free status was not achieved. During the median 55-month follow-up period, the disease-specific mortality was 10% in FTC and 2% in PTC. Orv Hetil. 2018; 159(22): 878-887.

Impact of body mass index on survival outcome in patients with differentiated thyroid cancer / Impacto do índice de massa corporal sobre o desfecho de sobrevida em pacientes com câncer diferenciado de tireoide

Abstract Introduction Increased body mass index is known to be associated with the high prevalence of differentiated thyroid cancers; however data on its impact on survival outcome after thyroidectomy and adjuvant therapy is scanty. Objective We aimed to evaluate the impact of body mass index on overall survival and disease free survival rates in patients with differentiated thyroid cancers. Methods Between 2000 and 2011, 209 patients with differentiated thyroid cancers (papillary, follicular, hurthle cell) were treated with thyroidectomy followed by adjuvant radioactive iodine-131 therapy and thyroid-stimulating hormone suppression. Based on body mass index, patients were divided into five groups; (a) <18.5 kg/m2 (underweight); (b) 18.5-25 kg/m2 (normal weight); (c) 26-30 kg/m2 (overweight); (d) 31-40 kg/m2 (obese) and (e) >40 kg/m2 (morbid obese). Various demographic, clinical and treatment characteristics and related toxicity and outcomes (overall survival, and disease free survival) were analyzed and compared. Results Median follow up period was 5.2 years (0.6-10). Mean body mass index was 31.3 kg/m2 (17-72); body mass index 31-40 kg/m2 was predominant (89 patients, 42.6%) followed by 26-30 kg/m2 seen in 58 patients (27.8%). A total of 18 locoregional recurrences (8.6%) and 12 distant metastasis (5.7%) were seen. The 10 year disease free survival and overall survival rates were 83.1% and 58.0% respectively. No significant impact of body mass index on overall survival or disease free survival rates was found (p = 0.081). Similarly, multivariate analysis showed that body mass index was not an independent prognostic factor for overall survival and disease free survival. Conclusion Although body mass index can increase the risk of thyroid cancer, it has no impact on treatment outcome; however, further trials are warranted.

Resumo Introdução Sabe-se que o aumento do índice de massa corpórea está associado à alta prevalência de câncer diferenciado de tireoide; entretanto, os dados sobre seu impacto no desfecho de sobrevivência após tireoidectomia e terapia adjuvante são escassos. Objetivo Objetivou-se avaliar o impacto do índice de massa corpórea nas taxas de sobrevida global e sobrevida livre de doença em pacientes com câncer diferenciado de tireoide. Método Entre 2000 e 2011, 209 pacientes com câncer diferenciado de tireoide (papilar/folicular/de células de Hurthle) foram tratados através de tireoidectomia, seguida de tratamento com iodo radioativo-131 adjuvante e supressão de hormônio estimulante da tireoide. Com base no índice de massa corpórea, os pacientes foram divididos em cinco grupos; (a) < 18,5 kg/m2 (baixo peso); (b) 18,5-25 kg/m2 (peso normal); (c) 26-30 kg/m2 (sobrepeso); (d) 31-40 kg/m2 (obesos) e (e) > 40 kg/m2 (obesos mórbidos). Várias características demográficas, clínicas e de tratamento e toxicidade associada e desfechos (sobrevida global e sobrevida livre de doença) foram analisadas e comparadas. Resultados O período médio de acompanhamento foi de 5,2 anos (0,6-10). O índice de massa corpórea médio foi de 31,3 kg/m2 (17-72); o índice de massa corpórea de 31-40 kg/m2 foi predominante (89 pacientes, 42,6%), seguido por 26-30 kg/m2, observado em 58 pacientes (27,8%). Observaram-se 18 recidivas locorregionais (8,6%) e 12 metástases distantes (5,7%). As taxas de sobrevida livre de doença e sobrevida global de 10 anos foram de 83,1% e 58,0%, respectivamente. Não foi encontrado impacto significativo do índice de massa corpórea nas taxas de sobrevida global ou sobrevida livre de doença (p = 0,081). Da mesma forma, a análise multivariada mostrou que o índice de massa corpórea não foi um fator prognóstico independente para sobrevida global e sobrevida livre de doença. Conclusão Embora o índice de massa corpórea possa aumentar o risco de câncer de tireoide, ele não tem impacto no resultado do tratamento; contudo, outros estudos são necessários.

Impact of body mass index on survival outcome in patients with differentiated thyroid cancer.

INTRODUCTION: Increased body mass index is known to be associated with the high prevalence of differentiated thyroid cancers; however data on its impact on survival outcome after thyroidectomy and adjuvant therapy is scanty. OBJECTIVE: We aimed to evaluate the impact of body mass index on overall survival and disease free survival rates in patients with differentiated thyroid cancers. METHODS: Between 2000 and 2011, 209 patients with differentiated thyroid cancers (papillary, follicular, hurthle cell) were treated with thyroidectomy followed by adjuvant radioactive iodine-131 therapy and thyroid-stimulating hormone suppression. Based on body mass index, patients were divided into five groups; (a) <18.5kg/m2 (underweight); (b) 18.5-25kg/m2 (normal weight); (c) 26-30kg/m2 (overweight); (d) 31-40kg/m2 (obese) and (e) >40kg/m2 (morbid obese). Various demographic, clinical and treatment characteristics and related toxicity and outcomes (overall survival, and disease free survival) were analyzed and compared. RESULTS: Median follow up period was 5.2years (0.6-10). Mean body mass index was 31.3kg/m2 (17-72); body mass index 31-40kg/m2 was predominant (89 patients, 42.6%) followed by 26-30kg/m2 seen in 58 patients (27.8%). A total of 18 locoregional recurrences (8.6%) and 12 distant metastasis (5.7%) were seen. The 10 year disease free survival and overall survival rates were 83.1% and 58.0% respectively. No significant impact of body mass index on overall survival or disease free survival rates was found (p=0.081). Similarly, multivariate analysis showed that body mass index was not an independent prognostic factor for overall survival and disease free survival. CONCLUSION: Although body mass index can increase the risk of thyroid cancer, it has no impact on treatment outcome; however, further trials are warranted.

Impact of surgical resection extension on outcome for primary well-differentiated thyroid cancer-a retrospective analysis.

BACKGROUND: The surgical resection extension in well-differentiated thyroid cancer is controversially discussed with the possibility of an overtreatment on the one hand against the risk of local disease recurrence. The aim of this study is to evaluate how the surgical resection extension with the adjunction of radioiodine therapy affects postoperative morbidity and the oncologic outcome of patients primarily treated for well-differentiated thyroid cancer. METHODS: All patients undergoing primary surgery for a well-differentiated, non-recurrent thyroid cancer from January 2005 to April 2013 at Tuebingen University Hospital were retrospectively analyzed. RESULTS: Papillary thyroid cancer (PTC) was present in 73 patients (including 27 papillary microcarinoma) and follicular thyroid cancer in 14 patients. Fifty-six of 87 patients (64%) underwent one-stage surgery, of which 26 patients (30%) received simultaneous lymph node dissection (LND). The remaining 31 patients (36%) underwent a two-stage completion surgery (29 patients with LND). Only in three patients a single lymph node metastasis was newly detected during two-stage completion surgery. Patients with LND at either one-stage and two-stage completion surgery had a significant higher rate of transient postoperative hypocalcemia. Postoperative adjuvant radioiodine therapy was performed in 68 of 87 patients (78%). After a median follow-up of 69 months [range 9-104], one local recurrence was documented in a patient suffering from PTC 23 months after surgery. CONCLUSION: No prophylactic two-stage lymphadenectomy should be performed in case of well-differentiated thyroid cancer to avoid unnecessary complication without any proven oncologic benefit.

Differentiated Thyroid Cancer-Treatment: State of the Art.

Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine. For DTC, surgery and radioiodine therapy followed by levothyroxine substitution remain the established therapeutic procedures. Even metastasized tumors can be cured this way. However, in rare cases of radioiodine-refractory tumors, additional options are to be discussed. These include strict suppression of thyroid-stimulating hormone (also known as thyrotropin, TSH) and external local radiotherapy. Systemic cytostatic chemotherapy does not play a significant role. Recently, multikinase or tyrosine kinase inhibitors have been approved for the treatment of radioiodine-refractory DTC. Although a benefit for overall survival has not been shown yet, these new drugs can slow down tumor progression. However, they are frequently associated with severe side effects and should be reserved for patients with threatening symptoms only.

Minimally invasive follicular thyroid cancer: treat as a benign or malignant lesion?

BACKGROUND: Follicular thyroid cancer is the second most common thyroid cancer, accounting for 10%-15% of all cases. Follicular thyroid carcinomas (FTCs) can be classified into two subtypes: classic (C), which exhibit both vascular and capsular invasion and minimally invasive (MI), which only has limited capsular invasion. Both types, like most well-differentiated thyroid cancers, are traditionally treated the same: a completion thyroidectomy usually followed by radioiodine ablation. We hypothesize that MI-FTC may behave more like a benign follicular adenoma rather than C-FTC and may not require total thyroidectomy and radioiodine. METHODS: A prospective thyroid database was screened for patients with follicular cell tumors. Data on recurrence rates, disease-free survival, and requirement for follow-up surgery and/or radioiodine were compared. Disease-free survival was determined by the Kaplan-Meier method. Analysis of variance and chi-square test were used to evaluate other factors. RESULTS: In total, there were 419 benign adenomas (87%), 21 MI-FTCs (4.5%), and 41 C-FTCs (8.5%). Patients with adenomas were younger (P = 0.035) and were more likely to be female (P = 0.001). Importantly, the 16-y disease-free survival was 100% in the adenoma group, 100% in the MI-FTC group, and 36.6% in the C-FTC group (P < 0.0001). CONCLUSIONS: MI-FTCs behave similar to adenomas with 100% disease-free survival with up to 16 y of follow-up. These data suggest MI-FTCs could be potentially treated by thyroid lobectomy alone like follicular adenomas and perhaps should be classified as a distinct clinical entity.

Incidental cervical metastases from thyroid carcinoma during neck dissection.

OBJECTIVES: To quantify and discuss the prevalence of unsuspected thyroid lymph node metastases discovered in specimens from neck dissection for head and neck squamous cell carcinoma (HNSCC) and discuss the impact on patient management. STUDY DESIGN: Retrospective study between May 2004 and January 2007. SETTING: University hospital. METHODS: Pathological analysis of cervical lymph node dissection performed during surgery for HNSCC in a total of 349 neck dissections in 266 consecutive patients. RESULTS: Twenty-one patients showed metastatic lymph nodes from thyroid cancer (prevalence 7.9%): 13 cases were metastatic from a papillary thyroid carcinoma and 8 cases from a follicular carcinoma. In 5 of the 21 patients, classical dissection was associated to recurrent nerve dissection and unilateral lobectomy; no thyroid carcinoma was found. Thirteen patients received radiotherapy for HNSCC. Follow-up comprised annual ultrasonographic examination of the neck and thyroid in these 21 patients. Total thyroidectomy was decided on in 5, with discovery of 3 micro-papillary thyroid carcinomas, in a single patient (complementary 131I treatment). No thyroid carcinomas were found for the other 4 patients. No patients died from thyroid carcinoma during follow-up (mean: 41 months). CONCLUSION: The prevalence of lymph node metastasis from thyroid carcinoma in cervical lymph node dissection during treatment of HNSCC seems higher (7.9%) than rates reported in the literature (0.3 to 1.6%). This may be due to the histopathological methods employed. Management of patients should be discussed in the light of thyroid ultrasonography and prognosis of HNSCC.

Ongoing risk stratification for differentiated thyroid cancer (DTC) - stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients.

INTRODUCTION: Adequate postoperative risk assessment currently constitutes the principle of DTC treatment and further management. The aim of the study - a retrospective assessment of risk factors influencing DTC relapse. MATERIAL AND METHODS: The study group consisted of 510 DTC staged pT1b-T4N0-N1M0, in whom total thyroidectomy and complementary radioiodine (RAI) treatment were carried out. In 71% papillary thyroid cancer was diagnosed, whereas in the remaining 29% - follicular thyroid carcinoma. Based on TNM classification from 1997, T1 feature was diagnosed in 11.6%, T2 in 35.1%, T3 in 8.4%, T4 in 9,4%, while in 35.5% - Tx. Lymph node metastases were present in 24.7% of cases. Median follow-up was 12.1 years (1.5-15.2). RESULTS: Age at DTC diagnosis, tumour diameter (T), lymph node metastases (N1), stimulated thyroglobulin, and RAI uptake in thyroid bed at qualification for RAI ablation significantly influenced freedom from progression time (FFP) in a multivariate analysis. When postoperative stimulated Tg was > 30 ng/mL the risk of relapse increased nearly six-fold, whereas the presence of N1 feature - four-fold. The total risk of relapse in the whole group was 12.55% while median FFP was 154.8 months. Five-year and 10-year FFP was 90.1% and 87.5%, respectively. CONCLUSIONS: Postoperative stimulated thyroglobulin level was the most potent, independent risk factor influencing FFP in DTC patients. Age above 60 years, an initial DTC stage (T and N features), and low RAI uptake in thyroid bed ( < 1%) were related to a higher risk of DTC relapse, whereas the investigated histopathological features were insignificant.

Current Guidelines for Postoperative Treatment and Follow-Up of Well-Differentiated Thyroid Cancer.

Well-differentiated thyroid cancer is increasing in incidence but the disease-specific mortality remains very low. The only effective adjuvant treatment is radioactive iodine ablation. Guidelines regarding the use and dosage of radioactive iodine depend on pathologic features of the primary and metastatic tumor that define risk. Long-term treatment includes thyroid-stimulating hormone suppression and surveillance with serum thyroglobulin and radiologic assessment for nodal recurrence.

Efficacy of Low-dose and High-dose Radioactive Iodine Ablation With rhTSH in Korean Patients With Differentiated Thyroid Carcinoma: The First Report in Nonwestern Countries.

OBJECTIVE: The aim of this study was to confirm the equivalent efficacy of recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW) as used in the preparation for low-dose and high-dose radioactive iodine (RAI) ablation in Korean patients with differentiated thyroid carcinoma. SUBJECTS AND METHODS: This retrospective study was designed to compare the efficacy of rhTSH and THW when used before ablation with low-dose (30 mCi) and high-dose (100 mCi) RAI, respectively. The study group included 570 patients with DTC with tumors staged T1 to T3, N0 to N1, and M0. Before RAI ablation, 190 patients used rhTSH and 380 patients matched by age, sex, T-stage, and N-stage used THW. The success of ablation was evaluated in each group based on 4 criteria: (1) stimulated thyroglobulin (sTg) <2 ng/mL, (2) sTg<2 ng/mL and negative diagnostic whole-body scan (DxWBS), (3) sTg<1 ng/mL, and (4) sTg<1 ng/mL and negative DxWBS. RESULTS: When both sTg<2 ng/mL and negative DxWBS were selected as criteria for success in patients treated with low-dose RAI, the success rates were 80.5% and 77.0% with rhTSH and THW, respectively (95% confidence interval, 5.9-12.8). Using both sTg<1 ng/mL and negative DxWBS as criteria, success rates were 78.2% and 71.8% with rhTSH and THW, respectively (95% confidence interval, 3.6-16.2). Using any criteria for success, low-dose RAI ablation with rhTSH was as effective as THW. Similar results were found for high-dose RAI ablation in patients using either rhTSH or THW. CONCLUSIONS: Low-dose and high-dose RAI ablation were equally effective using either rhTSH or THW before ablation in Korean patients with DTC, respectively.

[Draft of the best medical treatment in patients with low-risk thyroid cancer]. / Návrh optimálního lécebného postupu v lécbe nízkorizikového karcinomu stítné zlázy.

INTRODUCTION: The incidence of well-differentiated low-risk thyroid cancer have increased globally over the last three decades. Thyroid cancer treatment relates to a suitable surgical procedure and the use of adjuvant radio-iodine therapy in selected patients. Evaluation of prognostic factors and risk stratification are critical for determining appropriate treatment. Survival of patients with low-risk thyroid cancer is excellent. Appropriate choice of medical treatment resulted in full recovery in most patients. Relapse risk increases with the size of the primary tumor, along with the findings of the risk factors in men. METHODS AND RESULTS: Our study included a total of 1 980 patients in whom were diagnosed T1a and T1b tumors between the years 2003 to 2012. The population included 1 675 women (84.6 %) of average age of 45.22 years and 305 men (15.4 %) of average age of 50.0 years. The bulk of the file represented papillary carcinomas (1 868; 94.4 %), and smaller group of follicular carcinomas (112; 5.6 %). Patients were divided into four groups according to tumor size. Patients were evaluated according to risk factors: unifocality no other risk factors, multifocality - more bearings in thyroid tumor, metastases in regional lymph nodes, distant metastases or combination of risk factors. Group A: In the monitored set of 678 patients with papillary and follicular microcarcinoma up to 5 mm, during histological input, the findings revealed one bearing (unifocal type of cancer) in 566 patients. Multifocality was found in 112 patients, local nodal metastasis were demonstrated in 24 cases and pulmonary metastasis was discove-red in 1 case. Group B: In this group there were 576 study patients with papillary and follicular microcarcinoma size of 5-10 mm. Histological findings were captured input one bearing carcinoma in 434 patients, 142 patients with multifocality, in 53 cases of local nodal metastasis, and 1 case of bone metastases. Group C: In this group there were 467 study patients with papillary and follicular microcarcinoma size 10-15 mm. The histological initial finding captured unifocal type of cancer in 344 patients, multifocality in 123 patients, in 45 cases local metastases and in 3 cases of pulmonary metastases. Group D: 259 patients were monitored in this group with breast size 16-20 mm. At the initial finding was captured one bearing cancer in 188 patients, multifocality in 71 patients, in 24 cases evidence of local metastases and 2 patients had a case of distant lung metastases. In patients in whom risk factors were found, radioiodine treatment was indicated. This included 744 patients. In this group of patients after a year or more, relapse was observed in 74 patients (9.94 %). In 1 236 patients who did not undergo radioiodine treatment, there was a relapse in 49 patients (3.96 %). CONCLUSION: Based on our analysis, it is necessary to stratify the risk of relapse according to risk factors. In case of missed radioiodine therapy in patients with low-risk cancer without confirmed risk factors, it is also necessary to have regular clinical, laboratory and ultrasound examination. It is important to distinguish patients with risk factors that may contribute to disease recurrence. Only in this way, on one hand we prevent excessive treatment of patients with low-risk thyroid cancer which leads to increased cost of health care, and on the other hand prevent reduced level of care for patients with an increase in relapses.

Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia.

BACKGROUND: We examined outcomes in patients treated for radioactive iodine-induced sialadenitis (RAIS) and xerostomia with sialendoscopy. METHODS: Data was prospectively collected for all patients undergoing sialendoscopy for RAIS from a single institution. Interventional details and intraoperative findings were recorded. Qualitative data were obtained through patient examination, telephone interviews, and use of a standard quality of life questionnaire, Xerostomia Questionnaire. Quantitative data were obtained from patients who underwent sialometry. RESULTS: Twenty-six patients (24 women and 2 men; median age, 43 years; age range, 19-57 years) underwent interventional sialendoscopy after conservative management of symptoms proved unsuccessful. Sialadenitis was present in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the gland was the most common finding (22 patients) followed by stenosis (18 patients), inflammation (eight patients), and erythema (eight patients). Median follow-up time was 23.4±12.1 months. Sixteen patients (64%) reported complete resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and one (4%), regression in RAIS-related symptoms. Patients subjectively noted the following regarding their xerostomia symptoms: seven (31.8%) had complete resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one (4.5%), regression. Statistical analysis of the available sialometry data revealed a statistically significant difference in saliva production at 6 months following sialendoscopy for unstimulated saliva production (p=0.028). CONCLUSION: Sialendoscopy is an effective treatment option for the management of RAIS and xerostomia refractory to conservative therapy and medical management. Patients in our cohort report durable improvement in symptoms after intervention.

Effects of Salivary Secretion Stimulation on the Treatment of Chronic Radioactive Iodine-Induced Sialadenitis.

BACKGROUND: The aim of this prospective study was to investigate the effect of salivary stimulation therapy using pilocarpine (a cholinergic agent) on chronic radioactive iodine (RAI)-induced sialadenitis. METHODS: Sixty-one patients with a diagnosis of chronic RAI-induced sialadenitis after thyroidectomy and RAI therapy were enrolled in this prospective study. Patients received salivary stimulation therapy with pilocarpine (5 mg, 3 times daily) over a 3-month period. Subjective symptom scores were assessed using self-reported questionnaires. Salivary flow rates (SFRs) were measured and salivary gland scintigraphy (SGS) was performed to evaluate objective salivary gland functions. RESULTS: After salivary stimulation therapy, subjective symptom scores were significantly improved (p=0.002), but posttreatment unstimulated and stimulated SFRs did not differ significantly from pretreatment values. SGS parameters, that is, uptake ratio (UR), maximum accumulation (MA), Tmin, and maximum secretion (MS) of parotid and submandibular glands were nonsignificantly different after salivary stimulation therapy. CONCLUSION: The study shows that salivary stimulation therapy may reduce the subjective symptoms of RAI-induced chronic sialadenitis but does not significantly induce functional restoration.

Baseline stimulated thyroglobulin level as a good predictor of successful ablation after adjuvant radioiodine treatment for differentiated thyroid cancers.

BACKGROUND: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: This retrospective study accrued 64 patients (23 male and 41 female; mean age of 40±14 years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg<2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. RESULTS: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of ≤14.5 ng/ml was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg≤14.5 ng/ml and 12/36 (33%) patients with baseline STg>14.5 ng/ml ((p value<0.05). Age>40 years, female gender, PTS>2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. CONCLUSIONS: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg <2 ng/ ml, a negative DWBIS and a negative US neck).