Benign Thyroid Conditions Research Articles

BRAF Detection in FNAC Combined with Semi-Quantitative 99mTc-MIBI Technique and AI Model, an Economic and Efficient Predicting Tool for Malignancy in Thyroid Nodules.

Technology allows us to predict a histopathological diagnosis, but the high costs prevent the large-scale use of these possibilities. The current liberal indication for surgery in benign thyroid conditions led to a rising frequency of incidental thyroid carcinoma, especially low-risk papillary micro-carcinomas. We selected a cohort of 148 patients with thyroid nodules by ultrasound characteristics and investigated them by fine needle aspiration cytology (FNAC)and prospective BRAF collection for 70 patients. Also, we selected 44 patients with thyroid nodules using semi-quantitative functional imaging with an oncological, 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) radiotracer. Following a correlation with final histopathological reports in patients who underwent thyroidectomy, we introduced the results in a machine learning program (AI) in order to obtain a pattern. For semi-quantitative functional visual pattern imaging, we found a sensitivity of 33%, a specificity of 66.67%, an accuracy of 60% and a negative predicting value (NPV) of 88.6%. For the wash-out index (WOind), we found a sensitivity of 57.14%, a specificity of 50%, an accuracy of 70% and an NPV of 90.06%.The results of BRAF in FNAC included 87.50% sensitivity, 75.00% specificity, 83.33% accuracy, 75.00% NPV and 87.50% PPV. The prevalence of malignancy in our small cohort was 11.4%. We intend to continue combining preoperative investigations such as molecular detection in FNAC, 99mTc-MIBI scanning and AI training with the obtained results on a larger cohort. The combination of these investigations may generate an efficient and cost-effective diagnostic tool, but confirmation of the results on a larger scale is necessary.

Optimizing Thyroxine Dosage After Total Thyroidectomy: Understanding the Factors at Play.

Total thyroidectomy is evolving as the choice of treatment for non-malignant thyroid conditions. Therefore, an ideal method of thyroxine replacement is necessary to avoid the ill effects of under- and over-replacement in such patients. To assess the correlation between optimal thyroxine dose and potential variables like lean body mass (LBM), body surface area (BSA), body mass index (BMI), body weight, age, and sex in patients who underwent total thyroidectomies for benign multinodular goiters in our institute. A longitudinal cohort study was undertaken at the Government Medical CollegeThrissur, a tertiary care provider in India, between October 2018 and September 2019. One hundred adult patients who underwent a total thyroidectomy for various benign thyroid conditions were included. They were initially given thyroxine 75 µg upon discharge and received follow-up doses every two months until they achieved euthyroid status on two consecutive visits. The variables evaluated at this stage included age, sex, actual body weight, lean body weight, BMI, and biochemical data (triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH)). Correlation, multiple step-wise regression, and variance were carried out using EPI INFO version 7.2.2.6. The best predictors for optimum thyroxine dose were BSA (0.923, P < 0.01) and LBM (0.921, P < 0.01), compared with body weight (0.833, P < 0.01) and BMI (0.523, P < 0.01). In our study, the least significant factor was the age of the patient (r = 0.117, P < 0.01). There was no significant association between gender and thyroxine dose. The mean thyroxine dose was 1.87 µg/kg of the patient's body weight. The optimum thyroxine replacement based on BSA or LBM is a more ideal method than based on BMI or body weight alone.

Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules.

Thyroid fine-needle aspiration (FNA) is a principal diagnostic procedure for thyroid nodules. A specific cytomorphological structure, known as the thyroid spherule, is often seen in FNA specimens. The clinical significance of these spherules in terms of diagnosis and prevalence remains largely unexplored. We performed a retrospective study on 310 thyroid FNA specimens and categorized them according to the Bethesda System for Reporting Thyroid Cytopathology. The presence, size and number of thyroid spherules in each specimen were examined and these data were subsequently correlated with the clinicopathological features. Thyroid spherules were almost exclusively detected in benign cases, comprising 7.6% of all benign diagnoses. The average diameter of spherules in benign cases was 84.9 μm. Benign cases and cases with atypia of undetermined significance cases primarily exhibited low cellularity, while follicular neoplasms and malignant cases typically showed moderate to high cellularity. In the subgroup of FNA cases with moderate to high cellularity, spherules were identified in 12 (20%) of 59 benign FNA cases. Within this group, the sensitivity and specificity of thyroid spherules for detecting benign FNA cases were 20% and 100%, respectively. Our results suggest that the presence of thyroid spherules in FNA specimens can serve as a highly specific marker for benign thyroid conditions. The prevalence of spherule detection is strongly influenced by the cellularity. In cases with moderate to high cellularity, the identification of spherules can assist the cytopathologists in diagnosing thyroid FNA cases as benign.

Pre-surgery dietician counseling can prevent post-thyroidectomy body weight gain: results of an intervention trial

PurposeIt is widely accepted that patients experience weight gain after total thyroidectomy, and preventive measures should be recommended.MethodsA prospective study was designed to assess the efficacy of a dietetic intervention to prevent post-thyroidectomy weight gain in patients undergoing surgery for both benign and malignant thyroid conditions. Patients undergoing total thyroidectomy were prospectively and randomly assigned to receive a personalized pre-surgery diet counseling (GROUP A) or no intervention (GROUP B), according to a 1:2 ratio. All patients underwent follow-up with body-weight measurement, thyroid function evaluation and lifestyle and eating habits assessment at baseline (T0), 45 days (T1) and 12 months (T2) post-surgery.ResultsThe final study group encompassed 30 patients in Group A and 58 patients in Group B. The two groups were similar in terms of age, sex, pre-surgery BMI, thyroid function and underlying thyroid condition. The evaluation of body weight variations showed that patients in Group A did not experience significant body weight changes at either T1 (p = 0.127) nor T2 (p = 0.890). At difference, patients in Group B underwent a significant body weight increase from T0 to both T1 (p = 0.009) and T2 (p = 0.009). TSH levels were similar in the two groups, both at T1 and T2. Lifestyle and eating habits questionnaires failed to register any significant difference between the two groups, apart from an increase in sweetened beverages consumption in Group B.ConclusionsA dietician counseling is effective in preventing the post-thyroidectomy weight gain. Further studies in larger series of patients with a longer follow-up appear worthwhile.

Horner's Syndrome and Lymphocele Following Thyroid Surgery.

Horner’s syndrome (HS), caused by lesions of the 3-neuron oculosympathetic nerve pathway (ONP), includes the triad: blepharoptosis, miosis and anhidrosis (ipsilateral with ONP damage). Thyroid−related HS represents an unusual entity underling thyroid nodules/goiter/cancer−HS (T-HS), and post-thyroidectomy HS (Tx-HS). We aim to overview Tx-HS. This is a narrative review. We revised PubMed published, full-length, English papers from inception to November 2022. Additionally, we introduced data on post-thyroidectomy lymphocele/chylous leakage (Tx-L), and introduced a new pediatric case with both Tx-HS and Tx-L. Tx-HS: the level of statistical evidence varies from isolated case reports, studies analyzing the large panel of post-thyroidectomy complications reporting HS among the rarest side effects (as opposite to hypocalcemia), or different series of patients with HS due to various disorders, including T-HS/Tx-HS. Tx-HS is related to benign or malignant thyroid conditions, regardless the type of surgery. A pre-operatory rate of T-HS of 0.14%; a post-operatory rate of Tx-HS between 0.03% and 5% (mostly, 0.2%) are identified; a possible higher risk on endoscopic rather than open procedure is described. Incomplete HS forms, and pediatric onset are identified, too; the earliest identification is after 2 h since intervention. A progressive remission is expected in most cases within the first 2−6 months to one year. The management is mostly conservative; some used glucocorticoids and neurotrophic agents. One major pitfall is an additional contributor factor like a local compression due to post-operatory collections (hematoma, cysts, fistula, Tx-L) and their correction improves the outcome. The prognostic probably depends on the severity of cervical sympathetic chain (CSC) lesions: indirect, mild injury due to local compressive masses, intra-operatory damage of CSC like ischemia and stretching of CSC by the retractor associate HS recovery, while CSC section is irreversible. Other iatrogenic contributors to HS are: intra-operatory manipulation of parathyroid glands, thyroid microwave/radiofrequency ablation, and high-intensity focused ultrasound, and percutaneous ethanol injection into thyroid nodules. Tx-L, rarely reported (mostly <0.5%, except for a ratio of 8.3% in one study), correlates with extended surgery, especially lateral/central neck dissection, and the presence of congenitally—aberrant lymphatic duct; it is, also, described after endoscopic procedures and chest-breast approach; it starts within days after surgery. Typically low-fat diet (even fasting and parental nutrition) and tube drainage are useful (as part of conservative management); some used octreotide, local sealing solutions like hypertonic glucose, Viscum album extract, n-Butyl-2-cyanoacrylate. Re-intervention is required in severe cases due to the risk of lymphorrhoea and chylothorax. Early identification of Tx-HS and Tx-L improves the outcome. Some iatrogenic complications are inevitable and a multifactorial model of prediction is still required, also taking into consideration standardized operatory procedures, skillful intra-operatory manipulation, and close post-operatory follow-up of the patients, especially during modern era when thyroid surgery registered a massive progress allowing an early discharge of the patients.

Changing epidemiology and trends in incidence of thyroid cancer in England, 1985-2019

Abstract Background Thyroid cancer is 2-3 times more common in females and is currently the fastest growing cancer worldwide. Exposure to ionizing radiation is the only established risk factor for thyroid cancer. Other factors include obesity, history of benign thyroid conditions, and family history. We conducted a retrospective population-based cohort study to examine whether there have been changes in the incidence of thyroid cancer in England during the past four decades. Methods Individual level data for patients diagnosed with thyroid cancer in England during 1985-2019 were obtained from the Office for National Statistics/Public Health England. Average annual incidence rates were calculated by two age categories (0-49, 50+ years) and all ages combined during the seven five-year time periods (1985-89 to 2015-19). The percentage change in incidence was calculated as change in the average annual incidence rate from the first (1985-89) to the last time period (2015-19). Results During the 35-year study period, a total of 58,710 new cases of thyroid cancer were registered in England (27.3% males, 72.7% females). In young people aged 0-49 years, the average annual incidence rates increased by 375% in males and 438% in females (from 0.4/100,000 in 1985-89 to 1.9/100,000 in 2015-19 in males and from 1.3/100,000 in 1985-89 to 7.0/100,000 in 2015-19 in females). In older people aged 50+ years, the rates increased by 146% in males and 171% in females (from 2.4/100,000 in 1985-89 to 5.9/100,000 in 2015-19 in males and from 4.1/100,000 in 1985-89 to 11.1/100,000 in 2015-19 in females). Conclusions There has been a steady and substantial increase in the incidence of thyroid cancer in England over the past four decades. The largest increase in incidence was observed in young people aged 0-49 years. Some of this increase is due to enhanced surveillance and sensitive diagnostic methods, but other factors (e.g., obesity and history of benign thyroid conditions) need to be considered. Key messages

Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n= 7,425, 83% papillary). Cases were matched to controls (n= 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR= 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR= 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR= 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR= 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR= 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR= 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

A study of incidentally detected carcinoma in patients operated for benign thyroid disease: Is it more common than we think?

Aim: In this prospective study we analysed the incidence of carcinoma in patients operated with preoperative diagnosis of benign thyroid conditions, and correlate it with risk factors for further management. Methods: A prospective analysis of 94 patients that presented to a tertiary care centre in south India and diagnosed to have benign thyroid disease that required surgical management from April 2016 to October 2017. The postoperative thyroid specimen was analysed and any evidence of malignancy was noted. These patients were further evaluated and need for further treatment was analysed based on risk factors like advanced age, male sex and size of the tumour according to AGES, AMES and MACIS scoring systems. Results: In our study, 11 out of 94 patients operated for benign thyroid disease were found to have malignancy. Thus, the incidence of occult carcinoma of thyroid was significantly higher than that of the previously published literature in India, 11.7% vs 2-7%. The most common preoperative diagnosis was that of multinodular goitre. Conclusion : The incidence of malignancy in benign thyroid specimens was high in our study, but there is a need for longer follow up, to study the biology and behavioural patterns of these probably low grade tumours.

Epidemiology of Thyroid Cancer.

Epidemiology of Thyroid Cancer.

The Influence of Preoperative Thyroid Gland Volume On Intraoperative Time and Postoperative Complications for Total Thyroidectomy Patients

Objective: To determine the influence of preoperative thyroid gland volume on intraoperative time and postoperative complications for total thyroidectomy patients in a militaty tertiary hospital. Design: A cross-sectional analysis for data collected retrospectively from 106 consecutive patients who underwent thyroid surgery for various thyroid diseases at King Fahad Armed Forces Hospital in Saudi Arabia, between January 2015 and December 2019. Methods: A total of 106 patients (96 Female = 90.6% and 10 males = 9.4 %). Thyroid gland volumes were calculated preoperatively using ellipsoid model. FNA was done per American thyroid association guidelines. The patients underwent total thyroidectomy for benign and malignant thyroid conditions. The intraoperative time was measured starting from the skin incision till wound closure. Patients were followed for perioperative complications. The intraoperative time was correlated with preoperative ultrasonographic sizes of the thyroid glands. Independent sample t-Test done to compare mean US volumes in patients with complications and patients without complications. Results: The average thyroid gland volume was 43.48 ml the largest volume was 189.454 ml and the lowest volume was 1.46 ml. The average intraoperative time was 2 hours with longest time was 4 hours in a case with thyroid gland volume of 159.9 ml and the shortest intraoperative time was 1 hour and 1 minute in a case with thyroid gland volume of 58.44 ml. Total number of complications was 14 =13.2%. 1 case (0.9%) of expanding hematoma which required surgical drainage on a patient with thyroid gland volume of 34.59 ml, 7 cases (6.6%) of permanent hypocalcemia observed on patients with thyroid gland volumes of (9.16,14.21,19.81, 31.4, 37.57, 53.8, 159 ml). 4 cases (3.8%) of transient unilateral vocal fold immobility observed in patients with thyroid gland volumes of (11.55, 12.94, 26.98, 74.81ml) and 2 cases (1.9 %) of transient bilateral vocal folds immobility observed in patients with thyroid gland volumes of (60.53, 82.99 ml). Conclusion: The larger preoperative thyroid gland volume the longer operative time. Preoperative thyroid gland volume showed no significant influence on perioperative complications. Hence reviewing preoperative ultrasonographic thyroid gland volume may help the surgeon and operative staff preparations for larger cases.

Surgical outcomes in survivors of childhood cancer undergoing thyroidectomy: A single-institution experience.

Childhood cancer survivors (CCS) are at increased risk for thyroid disease, and many require definitive management with thyroid surgery. Despite this, there is limited evidence on surgical outcomes among CCS. We sought to evaluate postoperative outcomes at our institution among CCS undergoing thyroid surgery compared to patients without a history of primary childhood malignancy. Medical records were reviewed for 638 patients treated at the Children's Hospital of Philadelphia Pediatric Thyroid Center between 2009 and 2020. Rates of surgical complications, including recurrent laryngeal nerve (RLN) paralysis and hypoparathyroidism, among CCS were compared to patients with sporadic/familial thyroid cancer, Graves' disease, and other benign thyroid conditions. Operative time and intraoperative parathyroid hormone levels were also evaluated. There were no significant differences in long-term surgical complication rates, such as permanent RLN paralysis and hypoparathyroidism, between CCS and patients without a history of primary childhood malignancy (all p>.05). For all surgical outcomes, there were no significant differences in complication rates when CCS were compared to those undergoing surgery for sporadic/familial thyroid cancer or Graves' disease (all p>.05). CCS with benign final pathology had significantly higher rates of transient hypoparathyroidism compared to patients with benign thyroid conditions (p<.001). Our study suggests that CCS are not at higher risk of long-term complications from thyroid surgery when treated by high-volume surgeons within a multidisciplinary team.

Locally invasive classical papillary thyroid carcinoma with TSH receptor I568T mutation: case report.

SummaryAutonomous thyroid adenomas are caused by activating mutations in the genes encoding the thyroid-stimulating hormone receptor (TSHR) or mutations in the Gas subunit of the TSHR. Nodules with suspicious sonographic features should be submitted to fine-needle aspiration. Additional molecular testing may be performed to characterize the thyroid nodule’s malignant potential further. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation after an ultrasound showed suspicious sonographic features and fine-needle aspiration was ‘suspicious for malignancy’. The patient underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma. Most reports of TSHR I568T mutation have been seen in patients with benign thyroid conditions. While there is insufficient data to suggest that the TSHR I568T mutation causes aggressive thyroid malignancy, we believe clinicians who identify the presence of this mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.Learning pointsGermline and somatic activating mutations in the genes coding for the thyroid-stimulating hormone receptor (TSHR) have been frequently reported in familial and sporadic autonomous thyroid adenomas and non-autoimmune hyperthyroidism.Most reports of TSHR I568T mutation have been detected in patients with benign thyroid conditions.We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation and subsequently underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma.Clinicians who identify the presence of TSHR I568T mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.

Implications of radiofrequency ablation in patients undergoing thyroid surgery for benign disease in the United States

BackgroundRadiofrequency ablation is an alternative strategy for the management of benign thyroid conditions. We analyzed the proportion of patients who underwent thyroid surgery for benign conditions who would be potentially eligible for radiofrequency ablation. MethodsWe identified patients who underwent thyroid surgery from 2015 to 2019 at the study institution for Bethesda II cytopathology or toxic adenoma. Patients were considered potentially eligible for radiofrequency ablation if they had a dominant nodule >2 cm with or without compression symptoms, a dominant nodule <2 cm with compression symptoms, or a toxic adenoma. ResultsOf 411 patients in total, 284 (69.1%) would be eligible to consider thyroid radiofrequency ablation. In the radiofrequency ablation–eligible group, 20 (7.0%) experienced voice change after surgery, and 2 (0.7%) were dissatisfied or concerned about their scar. In the radiofrequency ablation–eligible group, 70 patients (24.6%) had malignancy diagnosed by final pathology, and 23 patients (8.1%) had cancers that were equal to or larger than 1 cm in size. ConclusionMany patients who undergo surgery for benign thyroid disease could be considered for radiofrequency ablation as an alternative treatment modality. Given the rate of occult malignancy, optimal evaluation of nondominant nodules before radiofrequency ablation and long-term thyroid surveillance for patients who undergo radiofrequency ablation should be further studied.

How does thyroidectomy for benign thyroid disease impact upon quality of life? A prospective study.

Choosing which patients to recommend surgery for benign thyroid conditions can be difficult due to the subjective nature of compressive thyroid and hormonal symptoms. The aim of this prospective study was to analyse changes in quality of life (QOL) following thyroid surgery using a validated disease-specific assessment tool, the thyroid-related patient-reported outcome (ThyPRO) questionnaire. Participants undergoing elective thyroid surgery for benign conditions were recruited. Patient demographics and clinical data were collected. ThyPRO consists of 85 questions grouped into 13 physical, mental and social symptom domains. Patients completed a ThyPRO questionnaire pre-operatively and at 6 weeks and 6 months post-operatively. ThyPRO items were scored according to protocol to produce 13 subscales. Repeated measures linear models with no random effects were performed using data for each outcome. Results were available for a total of 72 patients. The sample was predominately female (n = 63, 88%) with average age 49.8 years. The majority of patients underwent surgery for multi-nodular goitre. At 6 weeks post-operatively, significant improvement was demonstrated in the goitre, hypothyroid, hyperthyroid and anxiety symptom domains. At 6 months post-operatively, significant improvement was demonstrated in all but four domains. No domains demonstrated significant increase in impairment post-operatively. Patients had significant improvement in nine of 13 symptom domains following surgery. Patients did not experience a negative impact on QOL following surgery. Further studies with larger patient cohorts may be able to identify potential pre-operative predictive factors for a post-operative improvement in QOL for benign thyroid disease.

Performance of the ACR TI-RADS and EU TI-RADS scoring systems in the diagnostic work-up of thyroid nodules in a real-life series using histology as reference standard.

The ultrasonographic scores EU TI-RADS and ACR TI-RADS were introduced to give the clinicians indications for fine needle aspiration cytology (FNAC). The predictive role of these scores was never evaluated and compared in a surgical series of patients. The aim of this study was to evaluate the ex post diagnostic accuracy of EU TI-RADS and ACR TI-RADS in a real-life series of thyroidectomized patients and to evaluate the 'missing' thyroid cancer following the operational indications of these scores. Retrospective monocentric cohort study. In total, 255 patients (harboring 304 nodules) undergoing thyroidectomy for benign and malignant thyroid conditions were enrolled. The prevalence of thyroid malignancy for each class of ACR TI-RADS and EU TI-RADS, their diagnostic accuracy, the number of 'unnecessary' FNAC and the number of 'missed' cancers were evaluated. ACR TI-RADS and EU TI-RADS score had similar and satisfactory accuracy values for predicting thyroid malignancy (AUC: 0.835 for ACR TI-RADS vs 0.827 for EU TI-RADS). The ACR TI-RADS and EU TI-RADS categories (suspicious vs non-suspicious), age, sex and presence of a single nodule significantly and independently predicted the presence of malignancy in a logistic regression model. An ex post analysis according to the indications for FNAC for each score indicated that 31 and 16 cases of cancer would have been missed by ACR TI-RADS and EU TI-RADS scores, respectively. ACR TI-RADS and EU TI-RADS display a good performance in predicting thyroid cancer when histology is taken as reference standard, but additional clinical judgement is required to decide the indication for FNAC.

The clinical usefulness of chemokine C-X-C Motif Ligand 12 as a diagnostic marker for Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer worldwide. It is essential to develop methods for the accurate diagnosis of PTC to avoid unnecessary surgery. The chemokine C-X-C motif ligand 12 (CXCL12) is associated with various cancers. We aimed to investigate the efficacy of CXCL12 in the diagnosis of PTC in fine-needle aspiration (FNA) specimens. We prospectively collected samples from 58 patients who were scheduled for surgical treatment of PTC from 2013 to 2015. Tissue samples of 31 people with benign thyroid conditions were used as controls. Immunocytochemical and immunohistochemical staining for CXCL12 was performed on FNAs and corresponding tissue specimens. B-type Raf kinase (BRAF) V600E mutant protein expression and gene mutation were also analyzed to compare the clinical usefulness. : The mean age of the patients was 49.1 ± 1.4 years and 88.1% were women. Positive CXCL12 staining was observed in 6.5% of benign and in 98.3% of PTC samples; positive BRAF V600E mutant protein expression was found in 19.4% of benign and 93.1% of PTC samples. For the diagnosis of PTC for CXCL12 staining of FNA specimens, the calculated values were 93.1% sensitivity, 90.3% specificity, 94.7% positive predictive value, 87.5% negative predictive value, and 89.1% accuracy. CXCL12 had 100% sensitivity and specificity for the 12 cases of atypia of undetermined significance (AUS) diagnosed in FNA specimens. CXCL12 may be a useful diagnostic tool for PTC, especially when the FNA specimen is classified as AUS.

Incidental Thyroid Carcinoma Diagnosed after Total Thyroidectomy for Benign Thyroid Diseases: A Prospective Observational Study

Background: The term “incidental” denotes malignant tumors of the thyroid gland detected postoperative in surgical specimens resected for benign disease. As cancer, thyroid is the commonest endocrine malignancy and their incidence increases over the past 15-20 years. In Egypt, it represents 2.2% of total cancers. It constitutes 30% of endocrine malignancies and 12-49% of head and neck tumors. Objective: The aim of this study was to determine the incidence and histological features of incidental cancers in patients who had total thyroidectomy for benign thyroid diseases. Patients and Methods: This Study is a prospective, empirical study carried out at Al-Zahraa University Hospital during the period from April, 2016 to April, 2018. The study included 100 cases had total thyroidectomy of previously diagnosed benign thyroid diseases and fulfilled the inclusion criteria. Results: In this study, 100 patients underwent total thyroidectomy. The female (n=86) to male (n=14) ratio was 6.14: 1 and the age ranged from 19 to 69 years. The incidental carcinoma in this study found in 12 (12%) patients. The frequency of papillary carcinoma was 9 % of all thyroid diseases and 75% of the incidental thyroid cancer (ITC) (9/12). Also, frequency of follicular carcinoma was 1.4% of all thyroid diseases (three cases) and 16.66% of the ITC. Conclusion: The non-irrelevant incidence of ITC, the eventuality of multifocal and bilaterality and the possible occurrence of relapse support that total thyroidectomy without residuum is a valuable option for treating benign thyroid conditions.

Incidental Thyroid Carcinoma Diagnosed after Total Thyroidectomy for Benign Thyroid Diseases: A Prospective Observational Study

Background: The term “incidental” denotes malignant tumors of the thyroid gland detected postoperative in surgical specimens resected for benign disease. As cancer, thyroid is the commonest endocrine malignancy and their incidence increases over the past 15-20 years. In Egypt, it represents 2.2% of total cancers. It constitutes 30% of endocrine malignancies and 12-49% of head and neck tumors. Objective: The aim of this study was to determine the incidence and histological features of incidental cancers in patients who had total thyroidectomy for benign thyroid diseases. Patients and Methods: This Study is a prospective, empirical study carried out at Al-Zahraa University Hospital during the period from April, 2016 to April, 2018. The study included 100 cases had total thyroidectomy of previously diagnosed benign thyroid diseases and fulfilled the inclusion criteria. Results: In this study, 100 patients underwent total thyroidectomy. The female (n=86) to male (n=14) ratio was 6.14: 1 and the age ranged from 19 to 69 years. The incidental carcinoma in this study found in 12 (12%) patients. The frequency of papillary carcinoma was 9 % of all thyroid diseases and 75% of the incidental thyroid cancer (ITC) (9/12). Also, frequency of follicular carcinoma was 1.4% of all thyroid diseases (three cases) and 16.66% of the ITC. Conclusion: The non-irrelevant incidence of ITC, the eventuality of multifocal and bilaterality and the possible occurrence of relapse support that total thyroidectomy without residuum is a valuable option for treating benign thyroid conditions.

Keap1/Nrf2 Signaling: A New Player in Thyroid Pathophysiology and Thyroid Cancer.

The Keap1/Nrf2 pathway is a key mediator of general redox and tissue-specific homeostasis. It also exerts a dual role in cancer, by preventing cell transformation of normal cells but promoting aggressiveness, and drug resistance of malignant ones. Although Nrf2 is well-studied in other tissues, its roles in the thyroid gland are only recently emerging. This review focuses on the involvement of Keap1/Nrf2 signaling in thyroid physiology, and pathophysiology in general, and particularly in thyroid cancer. Studies in mice and cultured follicular cells have shown that, under physiological conditions, Nrf2 coordinates antioxidant defenses, directly increases thyroglobulin production and inhibits its iodination. Increased Nrf2 pathway activation has been reported in two independent families with multinodular goiters due to germline loss-of-function mutations in KEAP1. Nrf2 pathway activation has also been documented in papillary thyroid carcinoma (PTC), due to somatic mutations, or epigenetic modifications in KEAP1, or other pathway components. In PTC, such Nrf2-activating KEAP1 mutations have been associated with tumor aggressiveness. Furthermore, polymorphisms in the prototypical Nrf2 target genes NQO1 and NQO2 have been associated with extra-thyroidal extension and metastasis. More recently, mutations in the Nrf2 pathway have also been found in Hürthle-cell (oncocytic) thyroid carcinoma. Finally, in in vitro, and in vivo models of poorly-differentiated, and undifferentiated (anaplastic) thyroid carcinoma, Nrf2 activation has been associated with resistance to experimental molecularly-targeted therapy. Thus, Keap1/Nrf2 signaling is involved in both benign and malignant thyroid conditions, where it might serve as a prognostic marker or therapeutic target.

Patient Eligibility for Transoral Endocrine Surgery Procedures in the United States

Transoral endocrine surgery (TES) allows thyroid and parathyroid operations to be performed without leaving any visible scar on the body. Controversy regarding the value of TES remains, in part owing to the common belief that TES is only applicable to a small, select group of patients. Knowledge of the overall applicability of these procedures is essential to understand the operation, as well as to decide the amount of effort and resources that should be allocated to further study the safety, efficacy, and value of these operations. To determine what percentage of US patients undergoing thyroid and parathyroid surgery are eligible for TES using currently accepted exclusion criteria. Cross-sectional study of 1000 consecutive thyroid and parathyroid operations (with or without neck dissection) performed between July 1, 2015, and July 1, 2018, at 3 high-volume academic US thyroid- and parathyroid-focused surgical practices (2 general surgery, 1 otolaryngology-head and neck endocrine surgery). Eligibility for TES was determined by retrospectively applying previously published exclusion criteria to the cases. The primary outcome was the percentage of thyroid and parathyroid cases eligible for TES. Secondary outcomes were a subgroup analysis of the percentage of specific types of cases eligible and the reasons for ineligibility. The mean (SD) age of the 1000 surgical patients was 53 (15) years, mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 29 (7), and 747 (75.0%) of the patients were women. Five hundred fifty-eight (55.8%) of the patients were eligible for TES. Most patients with thyroid nodules with cytologically indeterminate behavior (165 of 217 [76.0%]), benign thyroid conditions (166 of 240 [69.2%]), and primary hyperparathyroidism (158 of 273 [57.9%]) were eligible for TES, but only 67 of 231 (29.0%) of patients with thyroid cancer were eligible. Among all 1000 cases reviewed, previous neck operation (97 of 441 [22.0%]), nonlocalized primary hyperparathyroidism (78 of 441 [17.7%]), and need for neck dissection (66 of 441 [15.0%]) were the most common reasons for ineligibility. More than half of all patients undergoing thyroid and parathyroid surgery in this study were eligible for TES. This broad applicability suggests that a prospective multicenter trial is reasonable to definitively study the safety, outcomes, and cost of TES.