Thyroid cancer.

The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. However, in the setting of these advances, disparities exist in the diagnosis and management of thyroid cancer. As new management options are becoming available for thyroid cancer, it is essential to support population-based studies and randomised clinical trials that will inform evidence-based clinical practice guidelines on the management of thyroid cancer, and to include diverse patient populations in research to better understand and subsequently address existing barriers to equitable thyroid cancer care.

A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. METHODS: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). RESULTS: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment. CONCLUSIONS: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

Discharge of postoperative patients with an opioid prescription is associated with increased persistent opioid use, healthcare expenditures and mortality: a retrospective cohort study.

BACKGROUND: The risk factors for persistent opioid use after surgical discharge and the association between opioid prescription at discharge and postoperative emergency department visits, readmission, and mortality are unclear. METHODS: This population-based retrospective cohort study involved opioid-naive patients who underwent surgical procedures from January 1, 2000 to November 30, 2020. The data source was Hong Kong Hospital Authority Clinical Management System electronic health record. The primary outcome was the incidence of new persistent opioid use. Other study outcomes included 30-day emergency department visits, 30-day readmission, and 30-day all-cause mortality. Multivariable logistic regression models were used to estimate the association between opioid prescription at discharge and persistent opioid use, emergency department visits, readmission, and all-cause mortality. RESULTS: Over a median follow-up of 1 month with 36 104 person-years, 438 128 patients (opioid prescription: 32 932, no opioid prescription: 405 196) who underwent surgical procedures were analysed, of whom 15 112 (3.45%) had persistent opioid use after discharge. Prescribing opioids on discharge was associated with increased risks of developing persistent opioid use (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 2.19-2.40, P<0.001), 30-day emergency department visits (OR: 1.28, 95% CI: 1.23-1.33, P<0.001), 30-day readmission (OR: 1.17, 95% CI: 1.13-1.20, P<0.001), and 30-day all-cause mortality (OR: 1.68, 95% CI: 1.53-1.86, P<0.001). CONCLUSIONS: In this large cohort of patients undergoing surgery, an opioid prescription on discharge was associated with a higher chance of persistent opioid use and increased risks of postoperative emergency department visits, readmission, and mortality. Minimising opioid prescriptions on discharge could improve perioperative patient outcomes.

Long-term outcome of patients treated with antithyroid drugs, radioactive iodine or surgery for persistent or relapsed Graves' disease.

BACKGROUND: The aim of this study was to compare long-term mortality, morbidity, and cumulative healthcare costs between antithyroid drugs, radioactive iodine, and surgical treatment for patients with persistent or relapsed Graves' disease. METHODS: Data on patients with persistent or relapsed Graves' disease between 2006 and 2018 were retrieved from the Hong Kong Hospital Authority. Hazard ratios (HRs) estimated by Cox proportional hazards regression models were used to compare the risks of all-cause mortality, cardiovascular disease, atrial fibrillation, psychological disease, Graves' ophthalmopathy, and cancer across treatment groups. The 10-year healthcare cost and change in co-morbidity status were also estimated. RESULTS: Over a median follow-up of 79 months (22 636 person-years), a total of 3443 patients (antithyroid drug 2294, radioactive iodine 755, surgery 394) were analysed. Compared with antithyroid drug treatment, surgery was associated with significantly lower risks of all-cause mortality (HR 0.40, 95 per cent c.i. 0.36 to 0.45), cardiovascular disease (HR 0.54, 0.48 to 0.60), atrial fibrillation (HR 0.11, 0.09 to 0.14), psychological disease (HR 0.85, 0.79 to 0.92), Graves' ophthalmopathy (HR 0.09, 0.08 to 0.10), and cancer (HR 0.56, 0.50 to 0.63). Patients who underwent surgery also had a lower risk of all outcome events than those in the radioactive iodine group. The 10-year direct cumulative healthcare cost was €14 754 for surgery compared with €17 390 for antithyroid drugs, and €17 918 for the radioactive iodine group. CONCLUSION: Patients who underwent surgery for persistent or relapsed Graves' disease had lower risks of all-cause mortality and analysed morbidities. The 10-year cumulative healthcare cost in the surgery group was lowest among the three treatment alternatives.

Outcomes of Graves' Disease Patients Following Antithyroid Drugs, Radioactive Iodine, or Thyroidectomy as the First-line Treatment.

BACKGROUND: The long-term outcomes of first-line choice among ATD, RAI, and thyroidectomy for GD patients remain unclear. OBJECTIVE: To compare the long-term morbidity, mortality, relapse, and costs of GD patients receiving first-line treatment. METHODS: A population-based retrospective cohort of GD patients initiating first-line treatment with ATD, RAI, or thyroidectomy as a first-line primary treatment between 2006 and 2018 from Hong Kong Hospital Authority was analyzed. Risks of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension were estimated using Cox proportional hazards regression models. The 10-year healthcare costs, change of comorbidities, and risk of relapse were compared across treatments. RESULTS: Over a median follow-up of 90 months with 47,470 person-years, 6385 patients (ATD, 74.93%; RAI, 19.95%; thyroidectomy, 5.12%) who received first-line treatment for GD were analyzed. Compared with ATD group, patients who had undergone surgery had significantly lower risks of all-cause mortality [hazard ratio (HR) = 0.363, 95% confidence interval (CI) = 0.332-0.396], CVD (HR = 0.216, 95% CI = 0.195-0.239), AF (HR = 0.103, 95% CI = 0.085-0.124), psychological disease (HR = 0.279, 95% CI = 0.258-0.301), diabetes (HR = 0.341, 95% CI = 0.305-0.381), and hypertension (HR = 0.673, 95% CI = 0.632-0.718). Meanwhile, RAI group was also associated with decreased risks of all-cause mortality (HR = 0.931, 95% CI = 0.882-0.982), CVD (HR = 0.784, 95% CI = 0.742-0.828), AF (HR = 0.622, 95% CI = 0.578-0.67), and psychological disease (HR = 0.895, 95% CI = 0.855-0.937). The relapse rate was 2.41% in surgery, 75.60% in ATD, and 19.53% in RAI group. The surgery group was observed with a significant lower Charlson Comorbidity Index score than the other 2 groups at the tenth-year follow-up. The mean 10-year cumulative healthcare costs in ATD, RAI, and surgery group was US$23915, US$24260, and US$20202, respectively. CONCLUSIONS: GD patients who received surgery as an initial treatment appeared to have lower chances of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension in the long-term when compared to those treated with ATD or RAI. The surgery group had the lowest relapse and direct healthcare costs among the 3 treatment modalities. This long-term cohort study suggested surgery may have a larger role to play as an initial treatment for GD patients.

Combining high-intensity focused ultrasound (HIFU) ablation with percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules.

OBJECTIVE: Assessing the 6-month efficacy of combined high-intensity focused ultrasound (HIFU) ablation with percutaneous ethanol injection (PEI) in benign thyroid nodules by comparing it with HIFU ablation alone. METHODS: One hundred and eighty-one (55.2%) patients underwent HIFU alone (group I) while 147 (44.8%) underwent concomitant HIFU and PEI treatment for solid or predominantly solid nodules (group II). Intravenous sedation and analgesia were given before the start of treatment. Extent of nodule shrinkage (by volume reduction ratio (VRR)), pain scores (by 0-10 visual analogue scale) during and after ablation, and rate of vocal cord palsy (VCP), skin burn, and nausea/vomiting were compared between the two groups. RESULTS: The mean amount of ethanol injected in group II was 1.3 ± 0.7 ml. The 3- and 6-month VRR were significantly greater in group II (60.41 ± 20.49% vs. 50.13 ± 21.06%, p = 0.001; and 71.08 ± 21.25% vs. 61.37 ± 22.76%, p = 0.001, respectively), and "on-beam" treatment time was significantly shorter in group II (26.55 min vs. 30.26 min, p = 0.001). Group II patients reported significantly lower pain score during treatment (2.24 ± 3.07 vs. 4.97 ± 3.21, p < 0.001) and 2 h after treatment (2.23 ± 2.50 vs. 2.97 ± 4.39, p = 0.044). Rates of VCP, skin burn, and nausea or vomiting were not significantly different (p > 0.05). CONCLUSIONS: The combined HIFU and PEI approach with improved administration of intravenous sedation and analgesia was associated with a significantly better 6-month efficacy than HIFU alone in benign thyroid nodules without compromising the safety and comfort of patients. KEY POINTS: • Concomitant HIFU and PEI have a better treatment efficacy than HIFU alone. • Concomitant HIFU and PEI have a comparable safety profile as HIFU alone.

Identifying predictive factors for efficacy in high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules - a retrospective analysis.

Objective: Since it is unclear whether clinical parameters can independently predict the subsequent treatment response following high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules, we aimed to examine clinical factors that may independently predict 12-month efficacy after HIFU treatment.Methods: One hundred and forty patients who had single ablation were categorized into two groups, those with 12-month nodule shrinkage above the median (Group I, n = 70) and with shrinkage below or equal to the median (Group II, n = 70). Baseline characteristics, treatment parameters, percentage change in serum TSH, Free thyroxine (FT4) and thyroglobulin (Tg) from baseline to Day 4 and appearance of microbubbles (hyperechoic marks (HEMs)) during treatment were compared between groups. To determine independent factors, a multivariate analysis was done by logistic regression analysis.Results: Baseline characteristics and treatment parameters were comparable between groups. However, on Day-4, group I had significantly lower serum TSH (0.49mIU/L vs. 0.84mIU/L, p = 0.011) and higher FT4 (22.11 pmol/L vs. 18.47 pmol/L, p = 0.008) than group II. The percentage change in TSH, FT4 and Tg were significantly greater in group I (p = 0.002, p = 0.009 and p = 0.001 respectively). The proportion of HEMs observed during treatment was also significantly higher in group I (42.69% vs. 31.72%, p = 0.030). Among the significant factors, the percentage change in FT4 was the only independent factor for 12-month shrinkage (OR = 1.018, 95%CI =1.003-1.032, p = 0.017).Conclusions: Percentage change in serum FT4 on post-treatment Day-4 was an independent blood parameter for the subsequent nodule shrinkage at 12 months. This finding could potentially facilitate the decision for earlier retreatment of treated nodules.

Utility of Activated Carbon Nanoparticle (CNP) During total Thyroidectomy for Clinically Nodal Positive Papillary Thyroid Carcinoma (PTC).

BACKGROUND: Activated carbon nanoparticle (CNP) is a novel tracer that may facilitate nodal dissection in clinically nodal positive (cN1) papillary thyroid carcinoma (PTC). The present study compared the nodal yield and surgical outcomes between surgery with CNP and without CNP. METHODS: Patients who underwent total thyroidectomy with therapeutic nodal dissection for cN1 PTC were given the option of intraoperative CNP injection. Among those who received CNP, 0.2 mL CNP suspension was injected in both thyroid lobes before dissection. Study endpoints included number of total and metastatic lymph nodes, inadvertently removed parathyroid glands (PGs), postoperative parathyroid hormone, calcium, and post-6-month thyroglobulin (Tg). Biochemical complete response (BCR) was defined as Tg ≤ 1 ng/mL and/or stimulated Tg ≤ 2 ng/mL. RESULTS: One-hundred and twenty patients (58.3%) received CNP, while 86 (41.7%) had surgery without CNP. Demographics, tumor characteristics, and operative time were comparable between the two groups. However, total mean number of normal and metastatic lymph nodes retrieved were significantly greater in CNP group (10.0 vs. 8.1, p = 0.032 and 4.5 vs. 2.7, p = 0.002, respectively). Rate of inadvertently removed PG was significantly less in CNP group (13.3% vs. 23.3%, p = 0.042). Postoperative Tg level and BCR were significantly lower in CNP group (9.9 ng/mL vs. 14.7 ng/mL, p = 0.297 and 82.4% vs. 72.9%, p = 0.002, respectively). However, large-sized ( ≥ 3 cm) PTCs had a significantly lower nodal staining rate than smaller-sized PTCs (10.3% vs. 69.4%, p < 0.001). CONCLUSIONS: CNP injection can facilitate therapeutic central nodal dissection by increasing the nodal yield rates and reducing inadvertent PG removal. To enhance its utility, a greater volume of CNP might be necessary in larger-sized (> 3 cm) PTCs.

Two-year efficacy of single-session high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules.

OBJECTIVES: Assessing the efficacy of single high-intensity focused ultrasound (HIFU) ablation in benign thyroid nodules beyond 12 months. METHODS: One hundred and eight patients underwent single HIFU treatment. Extent of nodule shrinkage [by volume reduction ratio (VRR)] and obstructive symptom score [by 0-10 visual analogue scale (VAS)] were evaluated for 24 months after treatment. VRR (%) was calculated based on the formula: [baseline volume - volume at visit] / [baseline volume] × 100. Binary logistic regression was performed to evaluate factors associated with 24-month treatment success (VRR ≥ 50%). RESULTS: After treatment, the mean (± SD) VRR at 3, 6, 12 ,18 and 24 months were 51.32 ± 20.71%, 62.99 ± 22.05%, 68.66 ± 18.48%, 69.76 ± 17.88% and 70.41 ± 17.39%, respectively, while the median (IQR) VAS at baseline, 6, 12 and 24 months was gradually lowered from 4.0 (2.0), 2.0 (1.0), 2.0 (1.0) to 1.0 (2.0), respectively. Sixty-three (58.3%) nodules had a further volume reduction (i.e. > 4.5%) from 12 to 24 months, while 22 (20.4%) nodules had a volume increase of > 4.5% from 12 to 24 months. Small pre-ablation nodule volume was a significant determinant for treatment success at 24 months (OR=1.045, 95% CI=1.021-1.092, p = 0.038). CONCLUSIONS: A majority of nodules had further volume reduction beyond 12 months after single HIFU ablation, but since one-fifth of nodules had a notable volume increase beyond 12 months, a longer period of surveillance would be necessary. Small pre-ablation nodule volume was a significant factor determining 24-month treatment success. KEY POINTS: • Small but significant nodule shrinkage continues beyond 12 months after single treatment. • Obstructive symptom continues to improve beyond 12 months after single treatment • Smaller-sized nodules have a greater chance of treatment success at 24 months.

Effect of perithyroidal lignocaine infusion (PLI) to pain experienced during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules.

OBJECTIVE: To assess whether perithyroidal lignocaine infusion (PLI) could provide additional analgesia in high-intensity focused ultrasound (HIFU) treatment of benign thyroid nodules for patients already receiving their usual intravenous doses of Pethidine and Diazemuls. METHODS: Two hundred and five patients who underwent HIFU ablation for a benign thyroid nodule were analyzed. Among them, 104 (50.7%) patients received PLI in addition to their boluses of Pethidine and Diazemuls before treatment (group I), while the rest (n = 101, 49.3%) received intravenous Pethidine and Diazemuls only (group II). After treatment, patients were asked to rate their overall pain experience on a visual analogue scale (VAS) (0-100) (0, no pain; 100, worse possible pain) during treatment. Binary logistic regression was performed to evaluate significant determinants for treatment pain including demographics, doses of medications, and treatment parameters. RESULTS: VAS was significantly lower in group I (51.30 vs. 63.79, p = 0.002). In the multivariate analysis, older age at treatment (OR = 1.036, 95%CI = 1.008-1.065, p = 0.011), lower BMI (OR = 1.202, 95%CI = 1.083-1.334, p = 0.001), higher Diazemuls dose (OR = 1.066, 95%CI = 1.018-1.114, p = 0.006), and use of PLI (OR = 2.096, 95%CI = 1.121-3.922, p = 0.020) were independent determinants of less treatment pain. CONCLUSIONS: PLI can provide additional analgesia in patients already receiving their usual intravenous doses of Pethidine and Diazemuls during HIFU ablation of benign thyroid nodules. Older age, lower body mass index, and greater Diazemuls (i.e., a sedative) dose are significantly associated with less treatment pain. KEY POINTS: • PLI provided an additional analgesic effect in HIFU ablation of thyroid nodules. • Older age and lower BMI were significantly associated with less pain. • Higher doses of Diazemuls lessened pain during HIFU ablation.

Two sequential applications of high-intensity focused ultrasound (HIFU) ablation for large benign thyroid nodules.

OBJECTIVE: High-intensity focused ultrasound (HIFU) ablation is a promising treatment for benign thyroid nodules but single application is less effective in larger-sized nodules. We aimed to assess the efficacy and safety of two sequential applications in larger-sized nodules. METHODS: Fifty patients underwent ablation of a large-sized nodule (baseline volume ≥ 20 mL and diameter ≤ 50 mm). Thirty-one (62.0%) patients underwent single application (group I) while 19 (38.0%) underwent two sequential applications (group II). Nodule shrinkage (by volume reduction ratio or VRR), pain scores during and after ablation, and rate of vocal cord palsy (VCP), skin burn, and nausea/vomiting were compared between the two groups. t test or the Mann-Whitney U test was used for continuous variables while chi-square test was used for categorical variables. To determine factors for VRR, multivariate analysis was done by logistic regression analysis. RESULTS: Total energy delivered and treatment time were significantly more in group II (p < 0.001 and p = 0.001, respectively). Total energy per nodule volume (kJ/mL) was also significantly greater in group II (1.01 kJ/mL vs. 0.57 kJ/mL, p < 0.001). The 6-month VRR was significantly greater in group II (56.74 ± 11.47% vs. 43.49 ± 12.03%, p = 0.004). Pain severity and rates of VCP, skin burn, and nausea/vomiting were comparable between the two groups (p > 0.05). Sequential application was an independent determinant of 6-month VRR (OR = 13.936, 95% CI = 1.738-197.399, p = 0.036). CONCLUSIONS: Sequential application led to better 6-month treatment efficacy than single application in large-sized nodules. Patients undergoing sequential application are not at greater risks of treatment-related side effects afterwards. KEY POINTS: • Sequential application produces better 6-month efficacy over single application for large-sized nodules. • Sequential HIFU application is well-tolerated and safe in patients with large-sized nodules. • Sequential application takes longer and requires larger amount of pethidine and diazepam.

Significance of hyperechoic marks observed during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules.

OBJECTIVE: To examine the association between the appearance of hyperechoic marks (HEMs) during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules and nodule shrinkage at 6 months. METHODS: One hundred and thirty-six patients who underwent HIFU for benign thyroid nodule were analysed. An independent person carefully examined the B-mode ultrasonography screen for the appearance of HEMs after each pulse. The proportion of HEMs (%) was calculated by: [(Number of pulses that resulted in HEMs) / (Total number of pulses given per treatment) × 100] while the nodule shrinkage was measured by volume reduction ratio (VRR) = [Baseline volume-volume at 6 months]/[Baseline volume] * 100. Treatment success was defined as VRR ≥ 50 %. RESULTS: Patients with HEMs (n=91) had significantly greater 6-month VRR than those without HEMs (n=45) (65.76 % vs. 36.76 %, p<0.001). By regression analysis, after adjusting for age and energy per pulse, smaller nodule volume at baseline (OR 1.143, 95 % CI 1.038-1.256, p=0.006) and appearance of HEMs (OR 275.44, 95 % CI 26.63-2848.98, p<0.001) were independent predictors for treatment success. CONCLUSIONS: The appearance of HEMs during treatment was an independent determinant of treatment success following single-session HIFU ablation of benign thyroid nodule. KEY POINTS: • HIFU is a safe and effective treatment for benign thyroid nodules. • Lower BMI and greater applied power increase likelihood of hyperechoic marks. • The appearance of hyperechoic marks during HIFU affects subsequent treatment outcome.

Sequential high intensity focused ultrasound (HIFU) ablation in the treatment of benign multinodular goitre: an observational retrospective study.

OBJECTIVES: Assessing the efficacy and safety of sequential high-intensity focused ultrasound (HIFU) ablation in a multinodular goitre (MNG) by comparing them with single HIFU ablation. METHODS: One hundred and four (84.6%) patients underwent single ablation of a single nodule (group I), while 19 (15.4%) underwent sequential ablation of two relatively-dominant nodules in a MNG (group II). Extent of shrinkage per nodule [by volume reduction ratio (VRR)], pain scores (by 0-10 visual analogue scale) during and after ablation, and rate of vocal cord palsy (VCP), skin burn and nausea/vomiting were compared between the two groups. RESULTS: All 19 (100%) sequential ablations completed successfully. The 3- and 6-month VRR of each nodule were comparable between the two groups (p > 0.05) and in group II, the 3- and 6-month VRR between the first and second nodules were comparable (p = 0.710 and p = 0.548, respectively). Pain score was significantly higher in group II in the morning after ablation (2.29 vs 1.15, p = 0.047) and nausea/vomiting occurred significantly more frequently in group II (15.8% vs 0.0%, p = 0.012). However, VCP and skin burn were comparable (p > 0.05). CONCLUSIONS: Sequential ablation had comparable efficacy and safety as single ablation. However, patients undergoing sequential ablation are at higher likelihood of pain in the following morning and nausea/vomiting after ablation. KEY POINTS: • Sequential HIFU ablation is well-tolerated in patients with two dominant thyroid nodules • More pain is experienced in the morning following sequential HIFU ablation • More nausea/vomiting is experienced following sequential HIFU ablation.

Evaluation of pain during high-intensity focused ultrasound ablation of benign thyroid nodules.

OBJECTIVE: To assess severity and factors of pain during high-intensity focused ultrasound (HIFU) ablation of benign thyroid nodules. METHODS: 128 patients who underwent a HIFU ablation for a benign thyroid nodule were analysed. All patients received a bolus of intravenous pethidine and diazepam before treatment. After treatment, patients were asked to rate their overall pain experience on a visual analogue scale (0-100) (0 = no pain; 100 = worse possible pain) during treatment, 2 h after treatment and the following morning. Binary logistic regression was performed to evaluate associated factors for pain including patient demographics, nodule size, body mass index (BMI) and treatment parameters. RESULTS: At T1, median (range) pain score was 65.0 (0.00-100.00). Only 16 (12.5 %) patients had a pain score of zero. In multivariate analysis, only lower BMI (OR 1.265, 95 % CI 1.102-1.452, p=0.001) and longer nodule diameter (OR 1.462, 95 % CI 1.071-1.996, p=0.017) were independent factors for pain score at T1 ≤ 65.0. CONCLUSIONS: A moderate to severe amount of pain was reported during ablation of benign thyroid nodules in over 50 % of patients. Patients' BMI and length of nodule diameter were independent variables for pain during HIFU ablation. KEY POINTS: • Pain was moderate to severe during HIFU ablation of thyroid nodules. • Only one in eight patients reported no pain during ablation. • Level of energy per pulse did not affect pain. • Patients with lower BMI and larger nodules had less pain.

Changes in serum thyroglobulin and antithyroglobulin shortly following high-intensity focused ablation of benign thyroid nodules in patients with positive antithyroglobulin status.

BACKGROUND: We aimed to describe changes in serum thyroglobulin (Tg) and anti-Tg autoantibody shortly following high-intensity focused ultrasound (HIFU) ablation in patients with positive anti-Tg status by comparing them with patients with negative anti-Tg and to correlate them with 6-month nodule shrinkage and treatment success. METHODS: From 2015 to 2017, patients who underwent HIFU ablation of a benign thyroid nodule were analysed. Serum Tg and anti-Tg were checked on treatment day (baseline) and 4 days after treatment. Anti-Tg >99 IU/ml were considered positivity. Percentage Tg or anti-Tg change = [Level on Day-4 - baseline level]/[Baseline level] × 100 while nodule shrinkage was measured by volume reduction ratio (VRR) = [Baseline volume - volume at 6 month]/[Baseline volume] × 100. Treatment success was defined as VRR >50%. RESULTS: Among the 276 eligible patients, 85 (30.8%) patients were positive for anti-Tg (Group I) while the others (n = 191, 69.2%) were negative (Group II). Relative to group II, Group I had a less significant Tg rise on Day 4 (4121.78 ± 9321.90% vs. 5711.53 ± 23487.20%, p = .013). There was a fall in anti-Tg on day 4 for group I (-11.56 ± 139.69%). This percentage anti-Tg drop significantly correlated with the 6-month VRR (ρ = -0.602, p = .030) but was not a significant factor of treatment success. CONCLUSIONS: Given the fact that the percentage anti-Tg drop correlated significantly with 6-month nodule shrinkage in group I, monitoring early anti-Tg change may help to predict the 6-month nodule shrinkage in patients with positive anti-Tg.

Measurement properties of ThyPRO short-form (ThyPRO-39) for use in Chinese patients with benign thyroid diseases.

PURPOSE: To evaluate the validity and reliability of a newly-translated Thyroid-specific Patient-Reported Outcome short-form (ThyPRO-39) instrument for ethnic-Chinese patients suffering from benign thyroid diseases. METHODS: The translation and cross-cultural adaptation of the English ThyPRO-39 were performed using the double forward translation, reconciliation, single backward translation, and cognitive debriefing, followed by a panel review. Cross-sectional data of 308 patients with benign thyroid diseases were utilized for this psychometric evaluation of ThyPRO-39 instrument. Convergent validity between similar construct in the ThyPRO-39, SF-6D, and SF-12v2 was assessed using Spearman correlations. The internal construct validity was assessed by corrected item-total correlations. Sensitivity of the ThyPRO-39 domain scores was determined by performing known group comparisons by independent t test. The internal consistency reliability was assessed by Cronbach's alpha coefficient. RESULTS: Significant floor effects were observed in 9 out of 13 domains of the ThyPRO-39. The hypothesized correlations between similar constructs in the ThyPRO-39 and the SF-12v2 and SF-6D were generally observed, supporting convergent validity. The internal construct validity was supported in most items, except eight items in six scales. Scale score of hyperthyroid symptoms of the ThyPRO-39 was significantly higher in the group with Graves' disease or hyperthyroid disease than the group without Graves' disease nor hyperthyroid disease. Scale scores of eye symptoms and impaired daily life were significantly higher in the incidental group than the non-incidental group. For six domains (hyperthyroid symptoms, hypothyroid symptoms, eye symptoms, tiredness, depressivity, and emotional susceptibility), Cronbach's alpha did not reach the recommended standard of 0.7. CONCLUSIONS: This was the first psychometric study to translate and adapt the ThyPRO-39 instrument for non-Caucasian patients, and report its validity and reliability for use in Chinese patients with benign thyroid diseases. Given the low item-total correlations in eight items and low internal consistency reliability in respective scales of the ThyPRO-39, we suggest that the improvement of those eight items should produce a more valid and reliable ThyPRO-39 instrument.

The significance of unrecognized histological high-risk features on response to therapy in papillary thyroid carcinoma measuring 1-4 cm: implications for completion thyroidectomy following lobectomy.

BACKGROUND: Although lobectomy is an alternative to total thyroidectomy (TT) for 1-4 cm papillary thyroid carcinoma (PTC) without high-risk features (HRFs) such as aggressive histology, vascular invasion, lymphovascular invasion (LVI), microscopic extrathyroidal extension, positive margin, nodal metastasis >5 mm and multifocality, these HRFs are not recognized until after surgery. Therefore, the chance of completion TT being required following lobectomy might be high. We evaluated the frequency of unrecognized HRFs and how they affected the response to therapy following TT and radioiodine (RAI). METHODS: Altogether, 1513 patients were analysed. Only 1-4 cm PTCs without recognizable HRFs were included. For response-to-therapy evaluation, only patients who had TT and post-RAI-stimulated thyroglobulin were analysed. Patients without an excellent response were defined as having 'incomplete response'. A multivariate analysis for incomplete response was performed. RESULTS: Of the 600 patients eligible for lobectomy, 257 (42·8%) had ≥1 unrecognized histological HRF before surgery. The prevalence of unrecognized HRFs was similar between 1-2 cm and >2-4 cm PTCs (P = 0·393). Of the 330 patients eligible for response-to-therapy evaluation, 260 (78·8%) had an excellent response while 70 (21·2%) had an incomplete response. LVI was the only independent unrecognized HRF for incomplete response (P = 0·021). CONCLUSIONS: The prevalence of unrecognized histological HRFs under the current recommendations is relatively high among 1-4 cm PTCs. Among the unrecognized histological HRFs, LVI was the only one which independently associated with an incomplete response (i.e. posing an increased risk of persistent/recurrent disease after curative surgery). These findings may have implications for patients who undergo lobectomy for 1-4 cm PTCs with no clinically recognizable HRFs under the current recommendations.

The percentage of serum thyroglobulin rise in the first-week did not predict the eventual success of high-intensity focussed ablation (HIFU) for benign thyroid nodules.

BACKGROUND: Given that high-intensity focussed ultrasound (HIFU) of benign thyroid nodules often causes a massive release of thyroglobulin (Tg) into the circulation, we hypothesised a greater initial Tg rise may result in a greater nodule shrinkage 6 months after ablation. METHODS: One hundred and five patients who underwent HIFU for symptomatic benign thyroid nodule from 2015 to 2016 were analysed. Serum Tg and anti-Tg autoantibody were checked on treatment day (baseline) and 4 d after treatment. The % of Tg rise = [serum Tg on day-4 - baseline serum Tg]/[baseline serum Tg] * 100 while the nodule shrinkage as measured by volume reduction ratio (VRR) = [baseline volume - volume at 6-month]/[baseline volume] * 100. Treatment success was defined as VRR >50%. RESULTS: At 6-month, the mean VRR was 62.2 ± 25.0% and 59 (76.6%) patients had treatment success. The mean baseline Tg level increased from 292.8 ± 672.7 ng/mL to 2022.7 ± 1759.8 ng/mL in the first-week. The % of Tg rise did not significantly correlate with either 3-month or 6-month VRR (p = 0.920 and p = 0.699, respectively). The mean % of Tg rise in the first week was not different between those with and without 6-month treatment success (368.2% vs. 1068.7%, p = 0.381). No clinical factors significantly correlated with treatment success. CONCLUSIONS: There was an almost seven-fold increase in the mean Tg level 4 d after HIFU ablation. The % of Tg rise in the first week did not appear to correlate with the 6-month nodule shrinkage or treatment success.

High-intensity focused ablation (HIFU) of single benign thyroid nodule rarely alters underlying thyroid function.

BACKGROUND: High intensity focused ultrasound (HIFU) is a promising ablation technique for benign thyroid nodules. However, its effect on underlying thyroid function remains unknown. We aimed to evaluate the 6 months changes in serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) after HIFU treatment. METHODS: Eighty-three consecutive patients who underwent single HIFU ablation for symptomatic benign thyroid nodule were analysed. Eligible patients had serum TSH and FT4 checked before treatment (baseline), 1 week, 3 and 6 months following HIFU treatment. Primary endpoints were hypothyroidism (FT4 < 12 pmol/L) and hyperthyroidism (FT4 > 23 pmol/L) in the 6 months following treatment. To express extent of nodule ablation relative to the total gland volume, an ablation volume ratio was calculated by [(Ablated nodule volume/total thyroid volume)/(total thyroid volume)] × 100. RESULTS: Relative to baseline, 1-week serum TSH significantly dropped (from 1.16 to 0.76 mIU/L, p < 0.001) while 1-week serum FT4 significantly rose (from 16.0 to 17.8 pmol/L, p < 0.001). However, 3- and 6-months TSH and FT4 did not changed significantly from baseline (p > 0.05). No patients developed hyperthyroidism while one (1.4%) developed hypothyroidism (FT4 = 11 pmol/L) at 3 months and 6 months. Interestingly, this patient had a previous lobectomy and an ablation volume ratio of 64.00%. CONCLUSIONS: Hypothyroidism following single HIFU ablation occurred rarely (1.4%) and resulted in little clinical relevance. Given that only one patient developed hypothyroidism following single HIFU ablation, it remains unclear how patients with different amount of parenchyma and relative extent of ablation may affect subsequent thyroid function.