Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Role of TSH Inhibition Therapy in the Postoperative Management of Patients with Differentiated Thyroid Cancer

Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.

The launch of a special issue on “Neck Dissection in Differentiated Thyroid Carcinoma” in Gland Surgery

Given the high incidence of cervical lymph node metastasis in differentiated thyroid cancer （DTC） and the rapidly increased importance of neck dissection in DTC, the journal of Gland Surgery is launching a special issue on ＂Neck Dissection in Differentiated Thyroid Carcinoma＂ in November Issue of 2013, inviting Dr. Xinying Li from Xiangya Hospital, China, as the guest editor.

BRAF V600E/TERT promoter mutations and NIS/TSHR expression in differentiated thyroid carcinomaand their clinical significance

Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma viral oncogene homolog B1) BRAF V600 E and TERT promoter mutations in differentiated thyroid carcinoma(DTC).The relationship between the two mutations and NIS/TSHR expression was also analyzed.Methods We have detected BRAF V600 E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC,52 cases of benign nodular goiter,and 31 cases of normal thyroid tissue.Results The BRAF V600 E mutation was detected in 142(62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma(PTC) and 1 case of follicular thyroid carcinoma(FTC)].TERT promoter mutations were detected in 18(7.9%) of 229 cases of DTC(14 cases of PTC and 4 cases of FTC),including the mutations C228T(0.9%) and C250T(7.0%),which were mutually exclusive.Moreover,11(61.1%) cases also harbored the BRAF V600 E mutation,which was not associated with gender,age,tumor size,lymph node metastasis,and recurrence risk stratification(P >0.05).The rate of TERT promoter mutation was higher in males,age ≥45,and in the middle/high-risk group(P <0.05),and the rate of simultaneous BRAF V600 E and TERT promoter mutations were higher in the middle/high-risk group(P <0.05).In addition,NIS positive rate in the concurrent BRAF V600 E and TERT promoter mutation group(45.5 %) was lower than in other groups(that is,the DTC group with BRAF V600 E or TERT promoter mutations(55.1%),the DTC group with no BRAF V600 E or TERT promoter mutation(57.5%),the nodules and normal group(75.9%);| r | = 0.171,P = 0.002).Conclusion TERT promoter mutations were lower in patients with DTC,with the C250 T mutation being the most common.The detection of BRAF V600 E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.

Characteristics of Persistent or Recurrent Differentiated Thyroid Cancer

Introduction: The differentiated thyroid cancer has generally an excellent prognosis after the treatment. The aim of this study is to describe the characteristics of persistent or recurrent differentiated thyroid cancers. Patients/ Methods: It is about a descriptive and retrospective study conducted from 392 patients followed for differentiated thyroid cancer. The data concerning the persistent or recurrent differentiated thyroid cancer have been collected from 1986 to 2015 in endocrinology service in Ibn Rochd CHU. Results: In total, twenty-four patients have shown the relapse or the persistency of their tumor, corresponding to the prevalence of 6.12 percent. The papillary carcinoma was dominant in 79 percent of cases and the follicular carcinoma in 21 percent of cases. The metastases were cerebral (two cases), lung (3 cases), bones (3 cases, Figure 1), and lymph nodes (9 cases). In our series, eighteen cases of persistent differentiated thyroid cancer have been found against six cases of recurrent differentiated thyroid cancer. Two cases of death at least three years of followed in our series and concerned the two cases of cerebral metastasis. Conclusion: The persistent or recurrent differentiated thyroid cancer rate is low in our series. The discovery of the relapse t is late.

Analysis of the incidence and influencing factors of hyponatremia before ^(131)I treatment of differentiated thyroid carcinoma

BACKGROUND Hyponatremia is a common clinical electrolyte disorder.However,the association between hyponatremia and acute hypothyroidism is unclear.Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy.AIM To analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer(DTC)before ^(131)I treatment.METHODS The study group consisted of 903 DTC patients who received ^(131)I treatment.The clinical data before and after surgery,as well as on the day of ^(131)I treatment were analyzed.According to the blood sodium level before ^(131)I treatment,patients were divided into the non-hyponatremia group and hyponatremia group.Correlations between serum sodium levels before ^(131)I treatment and baseline data were analyzed.Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia.RESULTS A total of 903 patients with DTC,including 283(31.3%)males and 620(68.7%)females,with an average age of 43.8±12.7 years,were included in this study.The serum sodium levels before surgery and ^(131)I treatment were 141.3±2.3 and 140.5±2.1 mmol/L,respectively(P=0.001).However,the serum sodium levels in males and females before ^(131)I treatment were lower than those before surgery.Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before ^(131)I treatment.In addition,the estimated glomerular filtration rate(eGFR)in males and females decreased before ^(131)I treatment compared with those before surgery(P=0.001).Moreover,eGFR in patients over 60 years and under 60 years decreased before ^(131)I treatment,when compared with that before surgery.There were no significant differences in serum potassium,calcium,albumin,hemoglobin,and blood glucose in patients before surgery and ^(131)I treatment(P>0.05).Among the 903 patients,23(2.5%)were diagnosed with hyponatremia before ^(131)I treatment,including 21 cases(91.3%)of mild hyponatremia and 2 cases(8.7%)of moderate hyponatremia.Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations,while moderate hyponatremia cases were mainly characterized by fatigue and dizziness,which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish.Correlation analysis showed a correlation between serum sodium before ^(131)I treatment and the preoperative level(r=0.395,P=0.001).There was no significant correlation between blood sodium and thyroid-stimulating hormone(TSH)levels and urine iodine before ^(131)I treatment(r=0.045,P=0.174;r=0.013,P=0.697).Univariate analysis showed that there were significant differences in age,sex,history of diuretic use,distant metastasis,preoperative blood sodium,blood urea nitrogen(BUN),eGFR,TSH and urinary iodine between the two groups(all P<0.05).Logistic regression analysis showed that factors such as history of diuretic use,distant metastases,preoperative sodium and BUN were all influencing factors of hyponatremia.The Hosmer and Lemeshow test(c2=2.841,P=0.944)suggested a high fit of the model.Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model(P<0.05).Preoperative serum sodium was a significant factor associated with pre-^(131)I therapy hyponatremia(OR=0.763;95%CI:0.627-0.928;P=0.007).CONCLUSION The incidence of hyponatremia induced by ^(131)I treatment preparation was not high.Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.

Correlation between sodium-iodide symporter expression and circulating tumor cell positivity in differentiated thyroid carcinoma

Objective We investigated the correlation between the expression of the sodium-iodide symporter(NIS) and the detection of circulating tumor cells(CTCs) in differentiated thyroid carcinoma(DTC).Methods NIS expression in differentiated thyroid and the positive rate of CTCs in the peripheral blood were determined by immunohistochemistry S-P and flow cytometry from the records of 172 cases of differentiated thyroid carcinoma.Results Seventy-six cases(44.2%) expressed NIS in the differentiated thyroid and 63 cases(36.6%) were positive for CTCs in the peripheral blood. There was a significant difference between N0 and N1 in the expression of NIS(χ~2 = 6.015, P = 0.014) and the positive rate of CTCs(χ~2 = 14.035, P = 0.001). N0 and N1 also differed significantly in the expression of NIS(r =-0.383,-0.610, P = 0.002, < 0.001). The differences in the NIS expression, but not in the positive rate of CTCs, were significant among the different pathological subtypes(χ~2 = 7.897, P = 0.005; χ~2 = 1.455, P = 0.228, respectively). There was a significant negative correlation between the highly differentiated type and intermediate differentiation type both in the expression of NIS and positive rate of CTCs(r =-0.591,-0.443, P < 0.001, P = 0.002). Conclusion There was a significant negative correlation between the expression of tissue NIS and positive rate of CTCs in the peripheral blood in DTC. The malignancy level and lymph node metastasis in differentiated thyroid carcinoma were negatively correlated with NIS expression and positively correlated with the positive rate of CTC.

Correlation between Central and Lateral Neck Dissection in Differentiated Thyroid Carcinoma

Objective: To determine the histopathological correlation between central and lateral neck metastasis in differentiated thyroid carcinoma, and its potential therapeutic impact. Although the central neck dissection (CND) is recommended in differentiated thyroid carcinoma, the indication for lateral neck dissection (LND) remains controversial. Design: Retrospective study. Methods and Main Outcome Measures: Pathological analysis of systematic ipsilateral central neck dissection (CND) and LND performed with total thyroidectomy in differentiated thyroid carcinoma was retrospectively reviewed according to “side” and to “patient”. Results: A total of 56 sides (46 patients) were suitable for analysis. Analysis by “side” revealed that CND and LND dissection samples were both negative in 15 cases, both positive in 32, CND was positive and LND was negative for 8 cases and CND was negative and LND was positive in 1 case. The combined presence of positive LND and positive CND was therefore observed in 32/40 “sides” and 26/46 “patients”. Analysis by “side” of the impact of the treatment decision to perform ipsilateral LND only in patients with positive CND and vice versa demonstrated a sensitivity, specificity, and accuracy of 97%, 65%, and 84%, respectively. Conclusions: In most cases, the presence of positive LND was associated with positive ipsilateral CND. The very low prevalence of positive LND in patients with negative CND may justify LND as a second step procedure only in patients with positive CND, except in the case of documented lateral neck metastasis.

Scabrous patrinia root inhibits circulating tumor cells in differentiated thyroid carcinoma–a clinical observation

Objective To observe the clinical inhibition of circulating tumor cells(CTCs) in differentiated thyroid carcinoma(DTC) by the extract of scabrous patrinia root(Huikangling).Methods Eighty-seven DTC patients tested positive for CTCs were randomly divided into two groups; all patients were treated with oral levothyroxine sodium in accordance with the DTC endocrine inhibition treatment criteria. Patients(n = 45) in the treatment group were provided the standard endocrine therapy along with oral Huikangling(0.4 g/tablet, 0.4 g × 3/time, 3 times/day, 12 weeks). Patients(n = 42) in the control group were only provided the standard therapy. After 4 and 12 weeks, CTCs in the blood were detected by flow cytometry.Results After 4 weeks of oral Huikangling treatment, CTCs were detected in 18(40%) and 29(69%) patients in the treatment and control groups, respectively; the difference was statistically significant(χ2 = 8.49, P < 0.05). After 12 weeks, CTCs were detected in 7(15.6%) and 17(44.7%) patients in the treatment and control groups, respectively; the difference was statistically significant(χ2 = 5.68, P < 0.05). Follow-up evaluation revealed two patients with lung metastasis and one patient with bone metastasis in the control group; one patient showed lateral neck lymph node metastasis without local recurrence in the treatment group.Conclusion Huikangling treatment reduces the number of CTC-positive DTC cases; however, further studies are needed to elucidate the underlying mechanisms.

Impact of Thyroglobulin on Survival and Prognosis of Differentiated Thyroid Cancer

Proper assessment of risk factors contributes to the principle management of differentiated thyroid carcinoma post operatively. Aim of the study: to investigate the effect of Thyroglobulin (Tg) levels on prognosis together with other risk factors for Differentiated Thyroid Cancer (DTC). Patients and methods: Medical records of all patients with DTC presented to Clinical Oncology and Nuclear Medicine Department referred from Diabetes & Endocrine unit (Internal Medicine Hospital) and Surgery Department Mansoura University from 2011-2016 were retrospectively reviewed. Patients with distant metastasis or who lost follow-up were excluded. So data of 220 patients were analyzed. Data collected included pre-surgical assessment, also surgical interference either total or near total thyroidectomy with or without lymph node neck dissection were reviewed. Different prognostic factors that affect progression free survival (PFS) include age, umorsize, ymph node status, ex, multifocality, capsular infiltration, vascular invasion and Tg level were evaluated through multivariate analysis. Results: Most of the patients included were <45 years (69.1%). Incidence of the disease was higher in female (80%) with papillary type predominance (80.9%). About 59.5% of cases presented with tumor size ≤ 2 cm and multifocality was reported in 13.6%. While 30% had lymph node metastasis, 11% had vascular invasion. Capsular infiltration was observed in 15% and most of them showed Tg level ≤ 10 ng/ml (68.2%). About 70% received ablative radioiodine. The 5-year Progression Free Survival (PFS) was 85%. On multivariate analysis of variable prognostic factors on PFS, we found that tumor size, age, lymph node status, capsular infiltration, Tg level and vascular invasion significantly affected PFS (P = 0.01, 0.005, 0.004, 0.005, 0.02, 0.003) respectively. While sex, pathological type and multifocality were not (P = 0.9, 0.4, 0.6) respectively. Conclusion: Postoperative Tg level is a statistically significant prognostic factor together with other risk factors.

Prevalence and Clinical Significance of Preoperative Thyroglobulin Antibodies in Differentiated Thyroid Cancer Patients

Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outcome of DTC. The objective of the present study was to retrospectively analyze the prevalence of PreopTgAb in patients diagnosed with DTC and its relation to thyroid cancer characteristics, staging, and disease outcome. A retrospective analysis of 109 DTC patients with reports of PreopTgAb was carried out. Clinicopathological parameters, including patient demographics (age and gender), TNM staging, histopathologic characteristics (type of pathology, vascular invasion, extrathyroid extension, carcinoma variant, multifocality), treatment (surgery, radioactive iodine), and outcome were recorded. The association of PreopTgAb was compared with the study variables and outcome of the disease using the Chi-square test and Mann-Whitney tests. The prevalence of PreopTgAb was 59.6%. Among the 54 PreopTgAb positive patients, 34 patients had an excellent response and 15 patients had an indeterminate response, while biochemically and structurally incomplete response was observed in 3 and 2 patients, respectively. PreopTgAb was not significantly associated with age (p = 0.919), sex (p = 0.650), pathology (p = 0.079), stage at diagnosis (p = 0.513), vascular invasion (p = 0.211), extra thyroid extension (p = 0.734), histologic variant (p = 0.877), multifocality (p = 0.361), and outcome (p = 0.360). Although we did not find a significant association between positive PreopTgAb and clinical characteristics and outcome of DTC, it can still be considered as a surrogate marker of DTC during follow-up.

^(131)I-chTNT-mediated radioimmunotherapy for non-uptaking ^(131)I pulmonary metastases from differentiated thyroid carcinoma

In this paper,the safety and efficacy of 131I-labeled mouse/human chimeric monoclonal antibody(131I-chTNT)-mediated radioimmunotherapy are evaluated because the patients have non-uptaking 131I pulmonary metastases from differentiated thyroid carcinoma(DTC).The 16 patients were injected intravenously by 29.6±3.7MBq·kg–1 using 131I-chTNT.The chest computer tomography was performed before treatment,as well as 28 and 70days after treatment.Responses and safety were assessed during the treatment.The results show that the 131I-chTNT infusion was well tolerated with the 12.5%complete response,18.8%partial response,25.0%progressive disease,and the 43.8%stable disease,indicating that most treatment-related adverse effects are mild transient and reversible.The131I-chTNT is promising for patients with non-uptaking the 131I pulmonary metastases from DTC.

Changes in percentage of lymphocyte subsets after ^(131)I treatment in patients with differentiated thyroid cancer

To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node me-tastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduc-tion compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The re-sults show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.

EFFECTS OF LEVOTHYROXINE ON BONE METABOLISM IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AFTER OPERATION AND ^(131)I ABLATION

Objective To investigate the effects of substitutive and suppressive doses of levothyroxine on bone metabolism in patients with differentiated thyroid carcinoma after surgery and 131I ablation. Methods The patients, who had received levothyroxine(L-T4) for at least 3 years for treating their differentiated thyroid carcinoma after surgery and 131I therapy, were classified into substitutive group and suppressive group according to the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH). We compared the levels of FT3, FT4, TSH, serum parathyroid hormone (PTH), serum calcium (Ca), serum phosphate (P), serum alkaline phosphates (ALP) and Bone mineral density (BMD) to those of healthy volunteers well matched for sex, age, menopausal status, and body mass index (BMI). Results No significant differences were found in the bone density and biochemical parameters of bone metabolism of the subjects treated with substitutive or suppressive doses of L-T4 compared with the control subgroup. No significant differences were observed among the subgroups according to accumulative doses of 131I. No bone fracture was found in all the patients. Conclusion The substitutive and suppressive doses of L-T4 are safe and necessary for patients with differentiated thyroid carcinoma after surgery and 131I therapy. Such treatment for 3 years is not associated with increased risk of osteoporosis. Much longer term of follow up is still needed in patients receiving substitutive and suppressive doses of L-T4.

Genetic factors for differentiated thyroid cancer in French Polynesia:new candidate loci

Background:Populations of French Polynesia(FP),where France performed atmospheric tests between 1966 and 1974,experience a high incidence of differentiated thyroid cancer(DTC).However,up to now,no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion.This research aimed to analyze the genetic factors of DTC risk among the native FP populations.Methods:We analyzed more than 300000 single nucleotide polymorphisms(SNPs)genotyped in 283 DTC cases and 418 matched controls born in FP,most being younger than 15 years old at the time of the first nuclear tests.We analyzed the genetic profile of our cohort to identify population subgroups.We then completed a genome-wide analysis study on the whole population.Results:We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations.We identified three regions associated with increased DTC risk at 6q24.3,10p12.2,and 17q21.32.The lead SNPs at these loci showed respective p-values of 1.66×10^(−7),2.39×10^(−7),and 7.19×10^(−7) and corresponding odds ratios of 2.02,1.89,and 2.37.Conclusion:Our study results suggest a role of the loci 6q24.3,10p12.2 and 17q21.32 in DTC risk.However,a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population.Moreover,the functional impact of these three new loci needs to be further explored and validated.

Comparison of Clinical and Ultrasonographic Features of Poorly Differentiated Thyroid Carcinoma and Papillary Thyroid Carcinoma

Background： The clinical behavior and management of poorly differentiated thyroid carcinoma （PDTC） are very different from papillary thyroid carcinoma （PTC）. By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. Methods： The data of 13 PDTCs and 39 ageand gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. Results： The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs （30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively） than those in PTCs （2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively） （P 〈 0.05）. The mortality rate of PDTCs was greatly higher than PTCs （P 〈 0.01）. Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs （3.1±1.9 cm vs. 1.7± 1.0 cm）. Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs （51.7% and 53.8%, respectively） （P 〈 0.05）. Conclusions： PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs.

Role of prophylactic central neck lymph node dissection for papillary thyroid carcinoma in the era of de-escalation

Thyroid cancer is the most common endocrine malignancy.While there has been no appreciable increase in the observed mortality of well-differentiated thyroid cancer,there has been an overall rise in its incidence worldwide over the last few decades.Patients with papillary thyroid carcinoma(PTC)and clinical evidence of central(cN1)and/or lateral lymph node metastases require total thyroidectomy plus central and/or lateral neck dissection as the initial surgical treatment.Nodal status in PTC patients plays a crucial role in the prognostic evaluation of the recurrence risk.The 2015 guidelines of the American Thyroid Association(ATA)have more accurately determined the indications for therapeutic central and lateral lymph node dissection.However,prophylactic central neck lymph node dissection(pCND)in negative lymph node(cN0)PTC patients is controversial,as the 2009 ATA guidelines recommended that CND“should be considered”routinely in patients who underwent total thyroidectomy for PTC.Although the current guidelines show clear indications for therapeutic CND,the role of pCND in cN0 patients with PTC is still debated.In small solitary papillary carcinoma(T1,T2),pCND is not recommended unless there are high-risk prediction factors for recurrence and diffuse nodal spread(extrathyroid extension,mutation in the BRAF gene).pCND can be considered in cN0 disease with advanced primary tumors(T3 or T4)or clinical lateral neck disease(cN1b)or for staging and treatment planning purposes.The role of the preoperative evaluation is fundamental to minimizing the possible detrimental effect of overtreatment of the types of patients who are associated with low disease-related morbidity and mortality.On the other hand,it determines the choice of appropriate treatment and determines if close monitoring of patients at a higher risk is needed.Thus,pCND is currently recommended for T3 and T4 tumors but not for T1 and T2 tumors without high-risk prediction factors of recurrence.

Low-dose and high-dose ^(131)I therapy for low and intermediate risk differentiated thyroid cancer: a randomized controlled clinical study

Objective To compare the ablation efficacy and therapy response with low-dose（1.1 GBq）and high-dose（3.7 GBq） 131I in postoperative patients with low and in-termediate risk DTC.Methods A total of 140 patients（37 males,103 females,age range:18-75 years）were enrolled from October 2014 to June 2015,and

Postoperative Stimulated Thyroglobulin Level and Recurrence Risk Stratification in Differentiated Thyroid Cancer

Background： Postoperative preablative stimulated thyroglobulin （ps-Tg） has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer （DTC）; however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management. Methods： Seven hundred and seven patients with DTC were included; low-risk （L; n = 90）, intermediate-risk （I; n = 283）, and high-risk （H; n = 334, 117 with distant metastasis [M 1 ]） patients were divided according to recurrence risk stratification. The M 1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis. Results： Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels （I vs. L： P 〈 0.05; H vs. 1： P 〈 0.001; H vs. L： P 〈 0.001）. The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml （1 vs. L： 61.5%, 63.3%）, 29.5 ng/ml （H vs, I： 41.9%, 92.6%）, 47.1 ng/ml （M1 vs. M0 in the H group： 79.5%, 88.9%） and 47.1 ng/ml （MI vs. M0 in all patients： 79.5%, 93.7%）. With the cut-offvalue at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment, Conclusions： Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.

Papillary Thyroid Carcinoma and Pregnancy: What Impact on Prognosis?

Introduction: The impact of pregnancy on the prognosis of papillary thyroid carcinoma (PTC) has been debated for several decades;however, no definitive conclusions have been reached. The main objective of this study is to demonstrate the short-term influence of pregnancy on the evolution and prognosis of PTC. Materials and Methods: A prospective descriptive and analytical study was conducted in the Endocrinology and Diabetology Department at the Hassan II University Hospital in Fez, including patients followed for papillary thyroid carcinoma presenting with a pregnancy during the year 2019 and 2020. The follow-up of these patients was continued until 1 year postpartum. We studied the clinical, paraclinical and therapeutic factors that could influence the prognosis of the disease. Results: We included 26 patients. Our study showed a significant correlation between recurrence and the presence of unfavorable histological signs (p = 0.02) as well as the initial Tg level (0.01). However, pregnancy was not an influencing factor (p = 0.41). Conclusion: Pregnancy does not seem to be a factor aggravating the prognosis of differentiated thyroid cancers.