Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis.

Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Health-related quality of life and radioiodine therapy in thyroid cancer patients: a before-and-after study.

OBJECTIVE: Thyroid cancers are on the rise, but the associated vital prognosis and long-term survival rates are very good. Therefore, treated patients' quality of life and psychological well-being are important considerations. The treatment usually involves surgery and radioactive iodine (radioiodine) ablation. This study aims to investigate potential effects of radioiodine ablation therapy on health-related quality of life, anxiety and depression symptoms, and nutritional status at 6 months post-therapy. METHODS: This study included 136 patients diagnosed with thyroid cancer. Absorbed doses to the salivary glands were estimated from dosimeters worn by patients. Patient health-related quality of life, psychological status and nutritional status were assessed before and 6 months after therapy using standardized questionnaires (including SF-36, Hospital Anxiety and Depression (HAD) scale). Statistical analyses included random-effects logistic and linear regressions adjusted for potential confounders. RESULTS: While no significant association was found between radioiodine exposure and anxiety or depression symptoms, or nutritional status, a significant increase in the SF-36 role physical sub- score was observed in relation with the salivary gland dose (ß= 6.54, 95%CI 2.71;10.36 for a 1-Gy increase). CONCLUSIONS: The findings suggest an improved physical health-related quality of life, namely reduced pain and functional impairment, 6 months after radioiodine therapy in thyroid cancer patients. No significant association was found between radioiodine exposure and mental health-related quality of life, anxiety or depression scores nor nutritional status. This study does not provide any evidence that radioiodine therapy has a potentially adverse effect on patient health-related quality of life.

[Molecular and other ancillary tests proposed by The Bethesda system for reporting thyroid cytopathology 2023]. / Les tests moléculaires et autres techniques ancillaires en cytologie thyroïdienne selon Bethesda 2023.

For the first time the 2023 version of The Bethesda System for Reporting Thyroid Cytology dedicates a whole chapter (chapter 14) to ancillary studies almost exclusively represented by molecular testing. The latest data reported bring some evidence that molecular testing could help to optimize the diagnostic performance of « indeterminate ¼ categories (AUS and NF). Other studies suggest a promising role to guide the management of suspicious of malignancy and malignant categories. Indeed, the recognition of prognostic and predictive biomarkers analyzed on cytological samples, regardless of how it is collected, has progressed thanks to advances in our knowledge of molecular abnormalities of thyroid tumors. The chapter 14 is presented here highlighting the current and emerging roles of « in-house ¼ and commercialized molecular testing as presented by TSBRTC.

Airway replacement using stented aortic matrices: Long-term follow-up and results of the TRITON-01 study in 35 adult patients.

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.

Effect of skip metastasis to lateral neck lymph nodes on outcome of patients with papillary thyroid carcinoma.

CONTEXT: Lymph node metastasis (N1) is a prognostic factor for disease recurrence in papillary thyroid carcinoma (PTC) patients. Skip metastasis is defined as only lateral N1 with negative central lymph nodes (LNs). OBJECTIVE: The aim of this study was to explore the outcome of PTC patients with skip N1. PATIENTS AND DESIGN: All patients who underwent a total thyroidectomy with ipsilateral central and lateral LN dissection for PTC from 1999 to 2019 in a high-volume endocrine surgery centre were included in this study. MAIN OUTCOME MEASURE: Demographic and outcomes-recurrence and disease-specific survival (DSS)-were compared between three groups: N1a (central N1 only), N1b-CL (central and lateral N1), and N1b-Skip (lateral N1 without central LN involvement). RESULTS: During the study period, 3046 patients had surgery for PTC, including 1138 with N1 (37%, 860 women, mean age: 44.8 years) comprising 474 N1a (42%), 513 N1b-CL (45%), and 151 N1b-Skip (13%). The median follow-up was 74 months (range 12-216 months). The recurrence rate in the N1b-Skip group was 13% (20/151) and 10% (47/474) in the N1a group. This was significantly lower than that in the N1b-CL group (27%, 140/513) (p < 0.0001). DSS at 10 years was 99% for group N1a, 98% for the N1b-CL, and 99% in the N1b-Skip group. CONCLUSION: The recurrence rate of N1b-Skip patients was lower than that of N1b-CL patients and similar to that of N1a patients. This result could be used as an indication for the modality of radioiodine therapy, and for the pattern of follow-up procedures.

Determining an energy threshold for optimal volume reduction of benign thyroid nodules treated by radiofrequency ablation.

OBJECTIVES: Radiofrequency ablation (RFA) is effective in reducing the volume of benign thyroid nodules. However, what parameters can influence the response to RFA is still unclear. The present study aimed to (1) investigate which ultrasound and technical parameters are potential determinants of the volumetric reduction; (2) develop a dose-response model, and (3) analyze the effects of RFA on ultrasound features. METHODS: In this retrospective study, three institutions treated patients with benign thyroid nodules according to the same protocol. The technical parameters were power and energy. The 1-year volume reduction ratio (VRR) was the reference standard of the response. The correlations of different parameters with VRR were analyzed and the association between several parameters and a VRR above 50% studied by uni- and multivariate analyses. The probit regression estimated the probability to achieve an effective response. RESULTS: One hundred fifteen patients were enrolled. The median power was 50 W and median total delivered energy 27,531 J. At 1-year follow-up, the median VRR was 64.0% and 87 (75.7%) nodules showed a VRR above 50%. Among all parameters, only baseline volume, total energy, and energy per volume were independently associated to a VRR > 50% (p = 0.001, p = 0.0178, p < 0.001 respectively). The probit regression analysis demonstrated that delivering 756 J/ml and 2670 J/ml gave a probability of VRR > 50% in 50% and 99% of patients, respectively. CONCLUSIONS: Considering the baseline nodular volume and delivering the adequate energy per volume allow optimizing technical and clinical success. KEY POINTS: • The effectiveness of radiofrequency ablation in treating benign thyroid nodules is negatively correlated to the volume of the nodule and positively correlated to the energy delivered per volume. • When planning the treatment, the total energy to deliver can be calculated by using a simple formula: nodular volume × 2670 J.

Learning curve for radiofrequency ablation of benign thyroid nodules.

Objective: To evaluate the effect of operator experience on the treatment outcomes of radiofrequency ablation (RFA) for benign thyroid nodules (BTN). Methods: Data from the 90 first RFA procedures of a single operator in treating benign thyroid nodules were prospectively collected and retrospectively analyzed. Patients were divided into 3 groups according to their chronological treatment rank: patients 1-30 (G1), 31-60 (G2) and 61-90 (G3). Clinical symptoms, volume reduction ratio (VRR), technique efficacy (TE) defined as a VRR > 50% and ablation ratio (AR) were compared between the three groups at 6 months follow-up. All complications and side effects were recorded. Results: No significant difference was observed in improvement of clinical symptoms after the RFA procedure between the three groups, with higher satisfaction however for pressure symptoms than for esthetic complaints (complete resolution 87.5% and 52.6%, respectively). In groups 1, 2 and 3, TE was 60%, 93.3%, 76.7%, VRR 54%, 65%, 60% and AR 13.1%, 34%, 34.6%, respectively. Thus, all ultrasound efficacy parameters (TE, VRR, AR) improved significantly between G1 and G2, with no difference between G2 and G3. Solely did AR improve in nodules ≤ 30 mL between G2 and G3 to reach a median value of 94.4% in G3 versus 57.1% in G2 and 13.7% in G1. Maximum values of TE and VRR (95.6% and 68%, respectively) were seen in nodules ≤ 30 mL in G2 at 6 months follow-up, with no improvement in G3 (84.2% and 63%, respectively). Both baseline volume and energy per volume were independently associated with VRR and AR. Three minor complications were recorded which all recovered totally after conservative treatment. Conclusion: There was a measurable learning curve in RFA for benign thyroid nodules regarding efficacy until 90 patients. VRR and AR can be used as proficiency markers. Only three transient complications occurred confirming the safety of the procedure.

Risk of recurrence in a homogeneously managed pT3-differentiated thyroid carcinoma population.

BACKGROUND: International guidelines for the management of differentiated thyroid cancers are based on the 7th TNM classification: pT3 tumors are defined as differentiated thyroid cancers (DTCs) measuring more than 4 cm in their greatest dimension that are limited to the thyroid or any tumor with minimal extrathyroidal extension (ETE; sternothyroid muscle or perithyroid soft tissues). Differences in clinicohistological features and prognosis among patients with pT3 tumors remain controversial, and studies regarding pT3 subgroups are lacking. OBJECTIVE: To analyze the prognosis of four subgroups of pT3 DTCs (papillary, PTC; or follicular, FTC). DESIGN AND SETTING: The data of patients who underwent surgery for pT3 DTC between 1978 and 2015 in a surgical department specialized in endocrine surgery were reviewed. Patients were classified into four groups as follows: the pT3a (≤ 10 mm with ETE), pT3b (10-40 mm with ETE), pT3c (> 40 mm without ETE), and pT3d groups (> 40 mm with ETE). Recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method. RESULTS: One thousand eighty-eight patients with pT3 DTC were included, of whom 311 (29%) had pT3a; 548 (50%), pT3b; 165 (15%), pT3c; and 64 (6%), pT3d. For the 916 patients with lymph node (LN) dissection, metastatic LNs were more frequent in the pT3b and pT3d groups (61 and 61%, respectively) than in the other groups (44% pT3a and 10% pT3c; p < 0.001). During the median follow-up period of 9 years (range, 2-38 years), recurrence occurred in 169 patients with T3 tumors (16%), including 18 with pT3a (6%), 100 with pT3b (18%), 20 with pT3c (12%), and 31 with pT3d (48%). In a multivariate analysis, LN metastases (< 0.0001), extranodal extension (p = 0.03), FTC (vs. PTC) (p = 0.006), pT3b (p = 0.016), and pT3d (p = 0.047) were associated with an increased risk of recurrence. The 5-year RFS rates were 94.5, 82.2, 91.1, and 50.3% for the pT3a, pT3b, pT3c, and pT3d groups, respectively (p < 0.01). CONCLUSION: Except for microcarcinoma, the risk of LN involvement is high and similar for the DTC patients with minimal ETE, regardless of the size of the tumor. The association of a tumor size of > 4 cm and ETE are associated with a poor prognosis and should justify the classification of these cases as a high-risk group. Other pT3 patients with no LN metastases could be individualized as a low-risk group.

Outcomes and Prognostic Factors in Radioiodine Refractory Differentiated Thyroid Carcinomas.

BACKGROUND: Outcomes vary among patients with radioiodine refractory (RR) differentiated thyroid cancer (DTC). The prognostic factors for survival are not well-known, resulting in difficulty in selecting patients for new targeted therapies. We assessed overall survival (OS) and cancer-specific survival (CSS) from RR-DTC to identify prognostic factors associated with survival. PATIENTS AND METHODS: The data on all cases of metastatic RR-DTC treated in our center from 1990 to 2011 were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method; associated prognostic factors were assessed using Cox's model. RESULTS: Of 153 cases of metastatic DTC, 59% (n = 91) met a criterion for RR: that is, 60% (n = 55) had at least 1 metastasis without (131)I uptake; 21% (n = 19) had progressive disease (PD) despite (131)I; 19% (n = 17) had persistent disease despite a cumulative activity of (131)I of ≥600 mCi. After the diagnosis of RR, median OS was 8.9 years (95% confidence interval [CI]: 5.4-NR); median CSS was 9.6 years (95% CI: 6.01-NR). In multivariate analyses, PD despite (131)I as a criterion for RR disease and the time from initial diagnosis of DTC to diagnosis of RR <3 years were the only independent prognostic factors for poor OS and CSS. Thyroglobulin doubling time (Tg-DT) was assessed in 31 of 91 cases. Among the 11 patients with Tg-DT for <1 year or undetectable Tg, 6 deaths occurred, whereas only 3 died of 20 patients with Tg-DT >1 year or negative Tg-DT. CONCLUSION: The identification of prognostic factors for decreased survival in RR-DTC may improve the selection of patients for targeted agents. IMPLICATIONS FOR PRACTICE: This study shows a great heterogeneity in terms of prognosis in radioiodine refractory differentiated thyroid carcinoma. Poorer prognosis is observed in patients with tumor progression or with a diagnosis of radioiodine resistance within 3 years after the initial diagnosis of thyroid cancer. Those findings could lead to improvements in the selection of patients for targeted therapies.

Can We Predict the Lateral Compartment Lymph Node Involvement in RET-Negative Patients with Medullary Thyroid Carcinoma?

BACKGROUND: Lateral lymph node dissection (LND) in the absence of macroscopic nodal metastasis remains controversial in sporadic medullary thyroid carcinoma (MTC). OBJECTIVES: The aims of our study were to determine the risk of lateral lymph node (LN) metastases with a focus on lateral contralateral N1, and to define a risk-adapted surgical treatment for these patients. METHODS: All patients who underwent surgery from 1980 to 2012 for previously untreated RET-negative MTC were reviewed. We focused on the lateral compartments of LN metastases and identified three groups: no lateral LN metastases, ipsilateral lateral (ILL)-LN metastases with no contralateral LN involvement, and contralateral lateral (CLL)-LN metastases. RESULTS: Overall, 131 patients underwent surgery for RET-negative MTC. A total thyroidectomy with LND was performed in 112 patients (85 %), including 97 patients who had an ILL-LND and 92 patients who had a CLL-LND. Lateral LN metastases (N1) occurred in 40 patients (37 %): 31 patients (32 %) had ILL-LN metastases with no contralateral LN involvement, and 9 patients (10 %) had CLL-LN metastases. The preoperative cut-offs for LN metastases in the ILL compartment were very low, with a smallest tumor size of 5 mm, and lowest serum calcitonin level of 38 pg/ml. Disease-free survival rates decreased from 92 % for patients with no lateral LN metastases to 41 % for patients with ILL-LN metastases and 0 % for patients with CLL-LN metastases. CONCLUSIONS: ILL-LND should be performed in every patient and only a minority of MTC patients with small micro-MTC, and low serum calcitonin levels should not have a CLL-LND.

Does extracapsular extension impact the prognosis of papillary thyroid microcarcinoma?

BACKGROUND: Extracapsular (EC) extension is a pejorative factor in papillary thyroid carcinoma (PTC). However, the impact of EC extension in microcarcinoma (micro-pT3) remains controversial, and all pT3 patients are currently considered to be at high risk of recurrence. OBJECTIVE: This study sought to determine the risk of recurrence in patients with micro-pT3 and to compare their outcomes with other pT3 (macro-pT3) and low-risk patients. PATIENTS AND METHODS: All consecutive patients who received surgery for PTC in our department from January 1978 to December 2011 were included in this study. We compared three patient groups: micro-pT3 (≤10 mm with EC extension), macro-pT3, and low risk, including pT1a-b s N0-x, pT1a-b m N0-x, and pT2 N0-x. Total thyroidectomy was performed with lymph node (LN) dissection in most cases, and radioiodine therapy was administered as needed. The median follow-up period was 6.7 years. RESULTS: A total of 2,482 patients were included in this study, including 178 micro-pT3 patients, 533 macro-pT3 patients, and 1,771 low-risk PTC patients. Recurrence was documented in 14 (7.9 %) micro-pT3 patients, 124 (23.3 %) macro-pT3 patients, and 36 (2 %) low-risk PTC patients. The micro-pT3 patients with LN metastases (N1) demonstrated a higher recurrence rate than the N0-x patients (14.8 vs. 4.8 %; p < 0.01), whereas the risk of recurrence among the T2 N0-x (5 %) and micro-pT3 N0-x (4.8 %) patients was similar (p = 0.95). CONCLUSION: Micro-pT3 N1 patients are at high risk of recurrence and should be treated aggressively. Because the outcomes of the micro-pT3 N0-x patients were similar to those of the low-risk PTC patients (pT2 N0-x), we suggest that micro-pT3 N0-x should be treated in a similar manner, with low-dose iodine-131 and recombinant human thyrotropin.

Next-Generation-Sequencing on fine needle aspirates in neck recurrence of thyroid cancers.

OBJECTIVES: Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on Formalin-Fixed Paraffin-Embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based Next Generation Sequencing (NGS) on the fine needle aspirate from thyroid cancer cervical recurrences to determine if this strategy is efficient in clinical practice. DESIGN/METHODS: A retrospective study of 33 patients who had had DNA and/or RNA-based NGS on ultrasound (US)-guided fine needle aspirates of cervical thyroid cancer recurrences in our Department from July 2019 to September 2022. RESULTS: In total, 34 DNA and 32 RNA-based NGS analyses were performed. Out of the 34 DNA-based NGS performed, 27 (79%) were conclusive allowing the identification of an oncogenic driver for 18 patients (53%). The most common mutation (n = 13) was BRAF c.1799T>A. Out of the 32 RNA-based NGS performed, 26 were interpretable (81%) and no gene fusion was found. The identification of a BRAFV600E mutation was decisive for one patient in our series, who was prescribed dabrafenib and trametinib. CONCLUSIONS: NGS performed on fine needle aspirates of neck lymph node metastases enabled the identification of an oncogenic driver alteration in 53% of the cases in our series of advanced thyroid cancer patients and could significantly alter patient management.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

[Thyroiditis]. / Thyroïdites.

The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

Prognostic impact of lymph node characteristics after therapeutic neck dissection for classic N1 papillary thyroid cancer.

BACKGROUND: The impact of lymph node characteristics on mortality and recurrence remains controversial. This study evaluated the prognostic impact of lymph node characteristics in a large, homogenous cohort of patients with therapeutic neck dissection for clinically N1 classic papillary thyroid cancer (PTC). METHODS: All consecutive adult patients with therapeutic central and lateral neck dissection for PTC at a French referral centre were prospectively enrolled from January 2000 until June 2021. The primary outcome was the impact of lymph node characteristics in predicting a disease event (persistence or recurrence), using univariable and multivariable logistic regression modelling. RESULTS: A total of 462 patients were included. Lymph node capsular rupture was seen in 260 patients (56.3 per cent). Median maximum lymph node size was 15 (i.q.r. 9-23) mm. The median central, lateral, and total lymph node ratio (LNR) was 0.50 (i.q.r. 0.22-0.75), 0.15 (i.q.r. 0.07-0.29), and 0.26 (i.q.r. 0.14-0.41), respectively. After a median follow-up of 93 (i.q.r. 50-149) months, 182 (39.4 per cent) patients had a disease event. After multivariable analysis, the number of harvested lymph node >35 (OR 2.33 (95 per cent c.i. 1.10-4.95)), presence of lymph node capsular rupture (OR 1.92 (1.17-3.14)), and total LNR >0.20 (OR 2.37 (1.08-5.19)) and >0.40 (OR 4.92 (1.61-15.03)) predicted a disease event. An LNR of 0.20 predicted a disease event with a sensitivity of 80.8 per cent and a specificity of 50.4 per cent. CONCLUSION: Disease persistence or recurrence after thyroidectomy with therapeutic neck dissection for classic PTC with preoperative nodal disease appears to depend on number of harvested lymph node, presence of lymph node capsular rupture, and total LNR.

Dysfunction of the Salivary and Lacrimal Glands After Radioiodine Therapy for Thyroid Cancer: Results of the START Study After 6-Months of Follow-Up.

Background: Understanding of changes in salivary and lacrimal gland functions after radioactive iodine therapy (131I-therapy) remains limited, and, to date, no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lacrimal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy-related risk factors for salivary/lacrimal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions. Methods: A cohort study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeter measurements. Salivary and lacrimal functions were assessed at baseline (T0, i.e., immediately before 131I-therapy) and six months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions. Results: There was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared with baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the past three months were found to be significantly associated with salivary or lacrimal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: for example, per 1-Gy increase in mean dose to the salivary glands, odds ratio = 1.43 [CI 1.02 to 2.04] for dry mouth sensation, ß = -0.08 [CI -0.12 to -0.02] mL/min for stimulated saliva flow, and ß = 1.07 [CI 0.42 to 1.71] mmol/L for salivary potassium concentration. Conclusions: This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lacrimal dysfunctions in DTC patients six months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, this study raises awareness of the risk factors for salivary disorders, and calls for longer follow-up. Clinical Trials Registration: Number NCT04876287 on the public website (ClinicalTrials.gov).

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Liver-kidney recipients with chronic viral hepatitis C treated with interferon-alpha.

Antiviral therapy with interferon-alpha (IFN-alpha) and pegylated IFN-alpha (PEG-IFN-alpha) for chronic hepatitis C (HCV)-infected kidney recipients remains controversial. IFN-alpha is not recommended in most cases because it induces severe acute graft rejection. However, IFN-alpha, as PEG-IFN-alpha, is associated with a more pronounced immune response, and is well tolerated in HCV-infected liver recipients without causing graft rejection. In combined liver-kidney transplant (LKT) recipients, IFN-alpha has been occasionally used and appears to be well tolerated. All LKT recipients with a functioning kidney and liver having a HCV replication and who needed IFN-alpha therapy have been included in the study. The occurrence of liver and/or renal acute rejection as well as the HCV replication has been collected. A total of 12 LKT patients treated with PEG-IFN-alpha plus ribavirin have been studied. No acute rejection was observed. Renal function remained stable during and after discontinuing treatment, without any graft dysfunction. Two patients had a partial viral response and four had a sustained viral response. All patients, whatever their viral response, had decreased liver-enzyme levels. Response to PEG-IFN-alpha therapy was correlated with steroid dose and transaminase level when PEG-IFN-alpha was started. These data suggest that the combination therapy of PEG-IFN-alpha plus ribavirin did not have a higher risk of acute kidney-graft rejection after liver-kidney transplantation.