Recurrent Differentiated Thyroid Carcinoma Research Articles

Central lymph node ratio is an important recurrence prognostic factor for pediatric differentiated thyroid cancer

BackgroundThe current risk stratification methods for Pediatric Differentiated Thyroid Carcinoma (DTC) are deemed inadequate due to the high recurrence rates observed in this demographic. This study investigates alternative clinicopathological factors, specifically the Central Lymph Node Ratio (CLNR), for improved risk stratification in pediatric DTC.MethodsA retrospective review of 100 pediatric DTC patients, aged 19 or younger, treated between December 2012 and January 2021 at the First Affiliated Hospital of Guangxi Medical University was conducted. Clinicopathological variables were extracted, and univariate logistic regression identified factors correlated with recurrence. Kaplan-Meier (KM) survival analysis and subsequent statistical tests were used to assess the significance of these factors.ResultsThe CLNR, with a cutoff value of 77.78%, emerged as a significant predictor of recurrence. Patients with a CLNR above this threshold had a 5.467 times higher risk of recurrence. The high CLNR group showed a higher proportion of male patients, clinically lymph node positivity (cN1), and extrathyroidal extension (ETE) compared to the low-risk group (p<0.05).ConclusionCLNR is a valuable predictor for recurrence in pediatric DTC and aids in stratifying patients based on Recurrence-Free Survival (RFS). For patients with a high CLNR, aggressive iodine-131 therapy, stringent TSH suppression, and proactive postoperative surveillance are recommended to mitigate recurrence risk and facilitate timely detection of recurrent lesions.

Diagnostic Performance of [18F]TFB PET/CT Compared with Therapeutic Activity [131I]Iodine SPECT/CT and [18F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[18F]tetrafluoroborate ([18F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [18F]TFB PET with high-activity posttherapeutic [131I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [18F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [131I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [18F]TFB PET/CT 40 min after injection of a median of 321 MBq of [18F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [131I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [18F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [131I]iodine positive, 32 lesions were [18F]TFB positive, and 52 were [18F]FDG positive. Three of the 30 [131I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [18F]TFB uptake and [18F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [18F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [131I]iodine scans. Therefore, it may help in the selection of patients for [131I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [18F]TFB uptake seems to be inversely correlated with [18F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC.

Risk factors for recurrence of differentiated thyroid carcinoma in children and adolescents: A retrospective cohort study.

This study aimed to provide a recent clinical evaluation of the outcome of treatment and the predictors of recurrence for Chinese children and adolescents with differentiated thyroid carcinoma (DTC). This is a retrospective cohort study at the Yunnan Cancer Hospital from May 2002 to August 2021. We analyzed several risk factors related to the recurrence of DTC in children and adolescents. The Chi-square test, Kaplan-Meier log-rank tests, and Cox regression analysis were used in the statistical analysis. A P-value <.05 was considered statistically significant. A total of 103 patients were enrolled, including 68 girls (66.0%) and 35 boys (34.0%) with a median age of 18 years (range: 7-20 years). All enrolled patients received standard treatment. Children (≤14years) tended to have multifocality and higher levels of thyroid imaging reporting and data system, higher pN stage, and higher American Thyroid Association (ATA) pediatric risk compared with adolescents (P < .05). The chief complaints and clinical treatment differed between children and adolescents. During a follow-up of 6 to 239 months (average 74.7 months, median 59 months), all patients survived, but recurrence occurred in 22 patients (22.4%). The disease-free survival rates at 1, 2, 5, and 10 years were 91.2%, 78.4%, 77.1%, and 77.1%, respectively. Univariate Cox regression and log-rank tests showed that positive preoperative thyroglobulin level, bilaterality, extrathyroidal extension, high pT/pN/pM stage, and high ATA pediatric risk were the risk factors for DTC recurrence in children and adolescents. Multivariate Cox regression found that extrathyroidal extension and ATA pediatric risk were independent risk factors for the recurrence of DTC in children and adolescents. Additionally, among the 38 cases with cN0 stage, one who had bilateral, and multifocal thyroid nodules experienced recurrence, while the remaining 37 cases with cN0 stage had no recurrence. In conclusion, compared with adolescents, children present with more highly malignant disease and are more prone to metastasis. The significant risk factors associated with the recurrence of DTC in children and adolescents were positive preoperative thyroglobulin level, bilaterality, high pT/pN/pM stage, extrathyroidal extension, and high ATA pediatric risk, with the latter 2 being independent risk factors. The surgical approach for cN0 patients should be personalized taking into account invasive features.

Thyroglobulin Cutoff Values for Detecting Excellent Response to Therapy in Patients With Differentiated Thyroid Cancer.

Serum thyroglobulin (Tg) is a biochemical marker for detecting persistent or recurrent differentiated thyroid carcinoma (DTC) post-thyroidectomy. Tg can indicate DTC before structural disease (SD) is visible with imaging procedures. This work aimed to evaluate the clinical performance of the Elecsys® Tg II assay at a Tg cutoff of 0.2 ng/mL for ruling out SD in adults with DTC after total/near-total thyroidectomy, with or without radioiodine ablation (RAI). Patients were enrolled into 2 cohorts: longitudinal (Tg assessed every 6 months over 2 years under thyroid-stimulating hormone [TSH] suppression therapy following thyroidectomy with or without RAI) and cross-sectional with confirmed SD (Tg assessed once >12 weeks after thyroidectomy). Analyses were performed for both cohorts combined and in the longitudinal cohort. The study included 530 clinically evaluable samples, the majority (n = 424 samples) from patients who had not received RAI treatment. Following correction for SD prevalence (4.97% in the longitudinal cohort), an Elecsys Tg II cutoff of 0.2 ng/mL ruled out SD with a negative predictive value of 99.9% (95% CI, 99.5%-100%). The assay had excellent sensitivity (98.5%-100%) and acceptable specificity (53.4%-53.5%) for detecting SD (Tg ≥ 0.2 ng/mL) for both cohorts combined and in the longitudinal cohort, with similar findings in RAI-treated and non-RAI-treated subgroups. In this cohort of DTC patients post-thyroidectomy, a Tg cutoff of 0.2 ng/mL was highly effective for ruling out the presence of SD under TSH-suppressed conditions, including in patients who had not received RAI treatment.

Hashimoto’s Thyroiditis: A Protective Factor against Recurrence in BRAF-Wild Type Differentiated Thyroid Carcinoma

A recent work analyzing the concomitant factors BRAF mutation (risk factor) and Hashimoto's thyroiditis (HT) (protective factor) found that the presence of HT reduced lymph node metastasis in BRAF-mutated papillary thyroid carcinoma. Whether this notion is upheld with respect to disease recurrence and differentiated thyroid carcinoma (DTC), however, is unknown. We aimed to investigate the effect of underlying HT in DTC patients and its influence on recurrence with a specific emphasis in BRAF-mutated tumors. A total of 469 patients were included. Patients were stratified according to BRAF and HT status. Multivariate regression analysis was conducted to determine protective and risk factors of disease recurrence in patients with DTC. HT was associated with less-aggressive carcinomas including more frequent microcarcinomas (HT: 45.0% vs. no-HT: 34.0%, p = 0.02), less lymph node involvement (HT: 16.4% vs. no-HT: 26.1%, p = 0.02), and less disease recurrence (HT: 2.9% vs. no-HT: 11.9%, p = 0.002). BRAF mutation was also significantly associated with higher rates of lymph node involvement (BRAF-mutant: 41.9% vs. BRAF-wild type: 14.6%, p < 0.001) and almost two times the rate of recurrence (BRAF-mutant: 14.9% vs. BRAF-wild type: 6.5%, p = 0.004). Underlying HT was the only protective factor determined, reducing the odds of developing recurrence by 70% (HR: 0.30, 95%CI: 0.11-0.88). In the BRAF-wild type cohort, regression analysis continued to determine HT as a protective factor (p = 0.03). However, in the BRAF-mutant cohort, HT was no longer an independent protective factor (p = 0.20) against recurrence. Sub-group regression analysis, including PTC patients, similarly found HT as a protective factor only in BRAF-wild type patients (p = 0.039) and not BRAF-mutant (p = 0.627). The presence of underlying HT is associated with less aggressive tumors and is an independent protective factor against DTC recurrence, reducing the risk by 70%. HT remains a protective factor in BRAF-wild type carcinoma, but not in patients with BRAF-mutant carcinoma. HT may potentially be considered as a parameter which enhances American Thyroid Association patient risk stratification.

Differentiated thyroid carcinoma recurrence: patterns and participating factors

Background Surgery for recurrent differentiated thyroid carcinoma is technically difficult, is demanding, and carries a higher risk for complications than de novo cases, so understanding the precipitating factors and patterns of recurrence will help in practicing maneuvers that can help in decreasing the recurrence. In this study, we examined these factors and patterns of recurrence. Patients and method A total of 40 patients with recurrence after differentiated thyroid carcinoma surgery were subjected to redooperations after clinical evaluation and all needed preoperative investigations. Preoperative and operative data and postoperative surgical and pathological outcomes were collected and analyzed. Results Our results revealed that the size of the primary tumor had a negative or inverse significant relationship with time passed till occurrence of recurrence or relapse (P=0.044). However, postoperative radioactive iodine therapy, postoperative thyroxine replacement therapy, unifocal tumors, and total thyroidectomy in primary procedure all were associated with a wider range of recurrence time with a higher mean±SD but did not reach a statistically significant level. Central compartment lymph nodes are the most affected group (95%) followed by level IV nodes, which had a 100% correlation with central group, and all lateral groups summed 82.5%. Conclusion The primary tumor size has a significant inverse relationship with time till occurrence of relapse. However, other factors did not reach a statistically significant level. Central compartment lymph nodes, which are very difficult for safe dissection in recurrent cases, are the most affected group, confirming being the first echelon nodes followed by level IV nodes. Therefore, prophylactic routine meticulous central dissection in the primary cases is advised for being much easier and safer.

Prognostic factors in patients with persistent/recurrent differentiated thyroid carcinoma after comprehensive treatment

Objective: To investigate the prognostic factors of patients with persistent/recurrent differentiated thyroid carcinoma (DTC) especially with external invasive persistent recurrent DTC after comprehensive treatment. Methods: The clinical data of 525 patients with persistent/recurrent DTC who underwent surgical treatment from August 2011 to June 2021 in the Department of Head and Neck Surgery of Jiangsu Cancer Hospital were retrospectively analyzed. The prognostic factors affecting overall survival (OS) and relapse-free survival (RFS) of persistent/recurrent DTC, especially external invasive persistent/recurrent DTC were analyzed. Results: Among 525 patients, 318 patients underwent thyroidectomy, 359 patients underwent central lymph node dissection, and 409 patients underwent lateral cervical lymph node dissection. Among 493 followed-up patients, 5-year OS and RFS were 95.10% and 89.60%, 8-year OS and RFS were 91.80% and 81.30%. Cox regression analysis showed that in patients with persistent/recurrent DTC after comprehensive treatment, age ≥55 years at reoperation after recurrence, male gender and distant metastasis were independent risk factors of OS (all P<0.05); while the simultaneous invasion of thyroid and lymph nodes, multiple organ invasion and the number of previous operations ≥2 were independent risk factors of RFS (all P<0.05). In patients with external invasive persistent/recurrent DTC after comprehensive treatment, age ≥55 years at reoperation after recurrence and male gender were independent risk factors of OS (both P<0.05); while multiple organ invasion and the number of previous operations ≥2 were independent risk factors of RFS (both P<0.05). Conclusions: Male patients aged 55 years old and above, with distant metastasis have a higher risk of poorer prognosis in persistent/recurrent DTC; while patients with simultaneous external invasion of thyroid and lymph nodes, multiple organ invasion and the number of previous operations ≥2 are more likely to relapse. For external invasive persistent/recurrent DTC, male patients aged 55 years old and above have a higher risk of poorer prognosis; while patients with multiple organ invasion and the number of previous operations ≥2 are more likely to have recurrence.

Male sex is not an independent risk factor for recurrence of differentiated thyroid cancer: a propensity score-matching study

Male patients have a significantly higher prevalence of advanced-stage thyroid cancer. However, sex differences in the risk of differentiated thyroid carcinoma (DTC) recurrence have not been fully elucidated. Therefore, the present study aimed to investigate male sex as a prognostic factor for DTC. We assessed 5566 patients with DTC who underwent thyroid surgery between January 2009 and December 2015 at Seoul St. Mary’s Hospital (Seoul, Korea). Clinicopathological characteristics and long-term oncologic outcomes between female and male patients with DTC were compared using propensity score matching to reduce selection bias. The mean follow-up duration was 99.9 ± 18.7 months. The recurrence rate was significantly higher in male patients than female patients before matching (3.3% vs. 2.2%, p = 0.030), and there was no significant difference in recurrence rates between the matched groups after matching (3.0% vs. 2.5%, p = 0.591). Based on Kaplan–Meier analysis, the two groups did not significantly differ in disease-free survival after matching. Multivariate analysis revealed that male sex was not an independent prognostic factor of DTC recurrence. Male sex did not have a significant effect on DTC recurrence. Further studies with larger cohorts are required to validate the findings of this study.

Usefulness of PET/CT with 18F-FDG in Patients with Differentiated Thyroid Carcinoma after Radioiodine Therapy: An Italian Multicenter Study.

Background: our aim was to assess the diagnostic performance and clinical impact of 18F-FDG PET/CT in patients with differentiated thyroid carcinoma (DTC), previously treated with surgery and radioiodine therapy (RAI). Methods: patients subjected to 18F-FDG PET/CT for suspected DTC recurrence in three Italian nuclear medicine units were evaluated. Two different clinical settings were identified: clinical setting 1 included patients (n = 40) that were enrolled according to the American Thyroid Association guidelines (i.e., negative 1311-WBS and Tg level > 10 ng/mL); and clinical setting 2, that encompassed subjects (n = 26) with serum Tg ≤ 10 ng/mL but morphological findings suspected of relapse. PET/CT’s impact was scored as significant if it provided an indication for surgery, or led to a novel therapeutic decision. Results: In total, 51/66 patients (77.3%) were 18F-FDG positive, while 15 (22.7%) were negative. PET/CT showed an overall sensitivity and specificity of 84.4% and 75%, respectively. Sensitivity was higher in clinical setting 1 (89.1%) as compared to clinical setting 2 (76.1%), although this difference was not statistically significant (p = 0.83). PET/CT influenced clinical management in 28 cases (42.4%), without a significant difference between the 2 groups of patients (p = 0.6). Conclusions: our preliminary data, although limited by the retrospective nature of the study and possible selection bias, suggest that 18F-FDG PET/CT may be utilized for the detection of DTC recurrence in different clinical settings, with a meaningful impact on clinical management.

Incidence of Recurrent Differentiated Thyroid Carcinoma in Paediatrics and Adolescents after Thyroid Surgery: A Meta-Analysis Study of Last 20 Years

Abstract Background: Childhood onset differentiated thyroid cancer is distinct from the adult-onset disease being more aggressive at the time of initial evaluation with a higher risk category for disease recurrence; however, it is ultimately less lethal. Unfortunately, there is no consensus regarding the means of follow-up, timing and management strategy regarding pediatric differentiated thyroid cancer. For these reasons, unique man-agement for children and adolescents with thyroid tumors are needed. Aim of Study: To locate relevant studies comparing incidence of recurrent differentiated thyroid carcinoma in paediatrics and adolescents after thyroid surgery modalities most commonly used in childhood onset differentiated thyroid cancer that are published in the period from June 1999 to June 2019, revising all these studies, and designing meta-analysis study to assess the overall results and define which management may provide better outcome and fewer rate of complications. Patients and Methods: The search strategy above will be viewed,and articles that appear to fulfil the inclusion criteria will be retrieved in full. Each article identified will be reviewed and categorized into one of the following groups: Included or excluded. When there will be a doubt, a second reviewer will assess the article and a consensus will be reached. Results: Medline databases (PubMed, Medscape, Science Direct. EMF-Portal) and all materials available in the Internet till 2019. Conclusion: All children will require life-long surveillance after thyroid surgery, especially for thyroid cancer. Paediatric thyroid cancer is rare. (The incidence of differentiated thyroid cancer is 1 per 1,000,000 in children less than 10 years of age). It is a treatable disease with an excellent prognosis. Treatment with radioactive iodine is recommended for most children after total thyroidectomy for papillary and follicular cancer. Radioiodine ablation should be carried about 4 weeks after surgery, with a diagnostic scan 6 months later. Regular review should include neck palpation, serum thyroglobulin, and ultrasound with cytology if necessary. In case of a cancer, follow-up ultrasound and TSH-suppressed thyroglobulin (Tg) level assessment is performed 6 months after initial therapy and at least annually thereafter, although it may be preferable to observe patients every 6 months for at least 5 years after diagnosis of more advanced initial or metastatic cancer. Assessment of free T4, T3, and TSH levels is indicated every 6 months, and 1-2 months after dosage changes. Calcitonin is a marker of recurrent disease in medullary cancer. This suggests that an aggressive operative approach to lymph node resection may be safer (lower recurrence, lower complications) in experienced hands than a less complete resection in a lower volume center.

The role of Tg kinetics in predicting 2-[18F]-FDG PET/CT results and overall survival in patients affected by differentiated thyroid carcinoma with detectable Tg and negative 131I-scan

PurposeThe aim of this study was to assess the potential role of thyroglobulin (Tg) kinetics in predicting 2-[18F]-FDG-PET/CT results and overall survival (OS) in patients affected by differentiated thyroid carcinoma (DTC) and suspected recurrence.MethodsOn hundred and thirty-nine patients were retrospectively included. All patients underwent 2-[18F]-FDG-PET/CT due to detectable Tg levels and negative [131I] whole-body scan. The last two consecutive serum Tg measurements before PET/CT were used for Tg-doubling time (TgDT) and Tg-velocity (Tg-vel) calculation. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for Tg, TgDT and Tg-vel for predicting PET/CT results.ResultsOne hundred and fifteen (83%) patients had positive PET/CT for DTC recurrence, while the remaining 24 (17%) negative. Stimulated Tg before PET and Tg-vel were significantly higher in patients with a positive PET/CT scan than negative scan (average Tg 190 vs 14 ng/mL, p = 0.006; average Tg-vel 4.2 vs 1.7 ng/mL/y, p < 0.001). Instead, TgDT was significantly shorter in positive scan (average TgDT 1.4 vs 4.4 years, p < 0.001). ROC curve analysis revealed the best Tg, TgDT and Tg-vel cutoff of 18 ng/mL,1.36 years and 1.95 ng/mL/y. In patients with Tg<18 ng/mL, the PET/CT detection rate was significantly lower in patients with low Tg-vel (p = 0.018) and with long TgDT (p = 0.001). ATA class risk, PET/CT results and Tg before PET were confirmed to be independent prognostic variables for OS.ConclusionsTg kinetics may help to predict 2-[18F]-FDG-PET/CT results in DTC patients with negative [131I]WBS and detectable Tg, especially in case of low-moderate Tg.

Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma.

Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC.

Thyroglobulin doubling time offers a better threshold than thyroglobulin level for selecting optimal candidates to undergo localizing [18F]FDG PET/CT in non-iodine avid differentiated thyroid carcinoma

PurposeTo investigate the potential role of serum thyroglobulin doubling time (TgDT) in predicting 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET/CT results in patients affected by differentiated thyroid carcinoma (DTC) who demonstrated a combination of positive Tg but a negative [131I] whole-body scan ([131I]-WBS).Materials and methodsInclusion criteria were (1) prior [131I] treatment for DTC, (2) negative subsequent [131I]-WBS, (3) no interfering anti-Tg antibodies, (4) three consecutive Tg measurements under the thyroid hormone replacement therapy to calculate TgDT before 2-[18F]FDG PET/CT, and (5) at least 6 months of clinical and/or imaging follow-up to ascertain the diagnosis. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to identify the optimal cutoff point for the last stimulated Tg and TgDT prior to [18F]FDG PET/CT.ResultsOne hundred and thirteen patients were included. Seventy-four (65%) patients had positive [18F]FDG PET/CT for DTC recurrence, while the remaining 39 (35%) negative. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of [18F]FDG PET/CT were 92%, 94%, 97%, 87%, and 93%. Patients with positive [18F]FDG PET/CT had higher Tg and TgDT than those with negative PET/CT. ROC curve analysis revealed an optimal Tg cutoff of 19 ng/mL (sensitivity 78%, specificity 85%, AUC = 0.844) and TgDT of 2.5 years (sensitivity 93%, specificity 87%, AUC = 0.911). TgDT threshold of 2.5 years predicted significantly (p = 0.023) better than Tg level PET/CT results.ConclusionsThe diagnostic performance of [18F]FDG PET/CT could be significantly improved when TgDT is less than or equal to 2.5 years, as compared with using the absolute Tg level.

TNM 8th edition in thyroid cancer staging: is there an improvement in predicting recurrence?

TNM 8th edition introduces changes in the staging of patients with differentiated thyroid carcinoma (DTC). This study aims at assessing the value of TNM 8th edition in predicting response to therapy and structural recurrence of DTC. Four hundred and eighty DTC patients were retrospectively evaluated by 7th and 8th editions of TNM staging system in relationship with risk stratification, response to therapy and recurrence of disease as defined by 2015 ATA guidelines. As compared to the 7th edition, TNM 8th led to downstage 136 patients (28.3%), with 97.5% of patients falling into lower stages (I-II) and only 2.5% remaining in higher stages (III-IV) (P < 0.001). Patients who were downstaged in stages I-II by TNM 8th were classified more frequently at intermediate-high risk (P < 0.001), had more frequently structural incomplete response to therapy (P = 0.009) and had higher risk of structural recurrence (P = 0.002) as compared to patients who were in the same TNM stages but were not downstaged. Specifically, the risk of structural recurrence was significantly higher in patients in whom the downstaging was induced by changes in tumour classification (hazard ratio (HR) 6.18, 95% CI 2.20-17.40; P = 0.001) but not in those who were downstaged for the increase in age cut-off (HR 2.80, 95% CI 0.86-9.19; P = 0.09). In conclusion, TNM 8th edition did not show reliability in predicting aggressiveness of DTC. In fact, the downstaging of DTC patients especially when performed due to changes in tumour classification may overlook patients predisposed to structural recurrence, potentially causing uncertainty in the therapeutic decision-making at the time of disease's diagnosis.

Outcome of 18f-Fluorodeoxyglucose Positron Emission Tomography (PET)-Directed Resections in Differentiated Thyroid Carcinoma (DTC): Experience in a Developing Country.

The aim of this study was to assess the accuracy of 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET scan) in localizing the disease in differentiated thyroid carcinoma patients undergoing re-operations. This is a retrospective analysis of a prospectively maintained data (December 2007 to December 2016). The patients included had elevated serum thyroglobulin (Tg) levels and negative iodine uptake (TENIS) and planned for re-operation with one or more accessible site of metastasis detected on FDG-PET scan. Clinical details, FDG-PET/CT findings, operative findings, histology, pre-, and post-operative Tg levels were recorded. Thirty-two patients were included. The mean age of the patients was 46.8 ± 15.8years (M:F = 1:1.6) and mean pre-operative Tg value was 247.6 ± 92.3ng/ml. FDG-PET disclosed a total of 77 hot spots in these 32 patients, 56 of which were surgically explored and resections performed. Patient- and lesion-based positive predictive value (PPV) of FDG-PET in detecting recurrent/metastatic DTC lesions was 87.5 and 71%, respectively. Remaining cases had granulomatous or nonspecific inflammatory lesions. A total of 12.5% of recurrent DTC patients explored could achieve biochemical cure. All these had disease confined to neck. Remaining patients continued to have high serum Tg level, though it fell substantially in majority of patients. False positive scans are frequent in regions with high prevalence of inflammatory diseases. Hence, FDG-PET directed re-operations should be taken up judiciously.

Label-free determination of thyroglobulin using template-probe double imprinted composites

Thyroglobulin (Tg) is an important index for the surveillance of differentiated thyroid carcinoma, and yet sensitive and specific protein detection still faces challenges in both biomedical research and clinical diagnosis. We described a novel approach to synthesize molecular imprinting polymers (MIPs)/hemin-graphene nanosheets (H-GNs) composites on the paper, using Tg and 3,3′,5,5′-tetramethylbenzidine (TMB, probe) as double templates. H-GNs with intrinsic properties can initiate the free-radical polymerization to prepare MIPs and catalyze the coloration of peroxidase substrates (TMB) for colorimetric detection. Template-probe double imprinting strategy enhanced the accessibility of the probe to the catalytic interface without interfering the specific recognition of template molecule. Under the optimized conditions, the gray intensity was proved to be proportional to the concentration of Tg in the range of 0.7-100 ng mL-1 with a detection limit of 0.1 ng mL-1 (1.5 fM). Anti-Tg antibodies and sample matrix did not affect the determination of the target protein, nor did they enhance the background noise. The use of paper-based device exhibited the advantages of low cost, easy handling and portability. It was supposed to be applied for Tg determination in serum to evaluate persistent or recurrent differentiated thyroid carcinoma.

Preoperative charcoal suspension tattoo for the detection of differentiated thyroid cancer recurrence.

Recurrent differentiated thyroid carcinoma can easily be detected by means of ultrasound (US) and thyroglobulin, and often requires further surgical intervention. Revision surgery is often a technical challenge with significant risk of complications, considering the altered anatomy, with a possibility of leaving behind residual neoplasm. Preoperative US-guided tattooing localization has been introduced to reduce and prevent these potential problems during revision surgery. Encouraging results have been reported in the literature. Under US guidance, the lesion is identified and 0.5-2 ml of colloidal charcoal is injected in its proximity using a 23 gauge needle. The extraction is accompanied by injection at constant pressure of charcoal in order to leave a trace of pigment along the path of the needle till the skin. From April 2008 to January 2016 we performed revision surgery in 27 patients for lymph-nodes metastasis in differentiated thyroid cancer, using the technique of preoperative charcoal tattoo localization. Our previous study on the first group of 13 patients published in 2012, reported the preliminary results in terms of success rate and complications. The tolerance of charcoal injection was good for all patients and the procedure was demonstrated to be useful, contributing to the removal of metastatic lesion in 93% of procedures. We have registered minor surgical complications during revision in the central compartment of the neck: Transitory hypoparathyroidism in 2 cases (11%) and transitory vocal cord paresis in 3 cases (16%). Based on these results, preoperative charcoal tattoo localization in revision surgery of the neck for differentiated thyroid cancer recurrence can be considered a safe technique, easy to perform, with low-costs and useful during surgical procedures, providing a significant reduction of iatrogenic damage and risks.

The efficacy of adjuvant radioactive iodine therapy for patients with recurrent differentiated thyroid carcinoma

The efficacy of adjuvant radioactive iodine therapy for patients with recurrent differentiated thyroid carcinoma

Impact of Patient Age and Histological Type on Radioactive Iodine Avidity of Recurrent Lesions of Differentiated Thyroid Carcinoma.

Age is a prognostic factor for recurrent differentiated thyroid carcinoma (DTC) and may be related to radioactive iodine (RAI) nonavidity. Indications for molecular-targeted drugs (MTDs) are currently limited to RAI-refractory DTC. Demonstrating refractoriness to RAI, mainly indicated by RAI nonavidity, may be a barrier to the introduction of MTDs for elderly patients. The present study was conducted to evaluate the impact of age and histological type on the RAI avidity of recurrent lesions of DTC. Two hundred fifty-eight patients (189 patients with classic papillary thyroid carcinoma [cPTC], 8 patients with follicular variant of papillary thyroid carcinoma, and 61 patients with follicular thyroid carcinoma), who underwent their first RAI whole-body scanning for recurrent DTC at our institution between 2004 and 2013, were retrospectively studied. Radioactive iodine uptake was determined by visible uptake by metastatic lesion(s) in a diagnostic RAI-whole-body scan. The prevalence of RAI-avid lung metastases in cPTC indicated a significant, inverse correlation with age (<55 years, 36.2%; ≥55 years, 3%; P < 0.001). By contrast, for follicular thyroid carcinoma, the prevalence of RAI avidity was not influenced by age. Similar tendencies were observed for lymph node metastases. Radioactive iodine avidity by metastatic lesions of cPTC in elderly patients, especially those older than 55 years, was seldom demonstrated. Adherence to a strategy of restricting MTD administration after confirmation of RAI refractoriness should be revisited for elderly patients. A strategy of omitting RAI treatment should be taken into account when considering age and histological type.

Cervical soft tissue recurrence of differentiated thyroid carcinoma after thyroidectomy indicates a poor prognosis

BackgroundWe investigated cervical soft tissue recurrence of differentiated thyroid carcinoma (DTC) after thyroidectomy, and these lesions exhibited no evidence that they were lymph nodes (LNs). MethodsBetween January 2012 and April 2016, consecutive 6308 patients underwent thyroid surgery for DTC at our center. Among them, we encountered 21 patients with recurrent cervical soft tissue lesions, none of whom had previously undergone fine needle aspiration biopsy (FNAB). ResultsThe 21 patients accounted for 0.33% of all 6308 patients, including twenty cases of papillary thyroid carcinoma and one case of follicular thyroid cancer. Approximately half (52.3%) of the recurrence were first detected by ultrasound (US). Eighteen lesions underwent complete preoperative US, but 6 lesions were misdiagnosed as metastatic LNs by US. Therefore, 54 age- and gender-matched recurrent or persistent LNs derived from DTC were randomly selected from the same database. The soft tissue lesions (mean size, 2.30 cm) were larger than the LNs. Fewer hyperechogenic hila and punctuations were found in the group of soft tissue recurrence (P < 0.05). During follow-up, distant metastasis was detected in 38.1% of patients in the soft tissue recurrence group. The distant metastasis rates showed that local soft tissue recurrence led to a poorer prognosis than cervical LN persistence or recurrence (P = 0.00). ConclusionsAlthough the incidence of DTC recurrence in cervical soft tissue was low, it may be a predictor for distant recurrence. To minimize the risk, a long-term postoperative evaluation, preferably with US, should be performed.