Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer.

OBJECTIVES: The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC). MATERIALS AND METHODS: This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test. RESULTS: In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05). CONCLUSION: 2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC. CLINICAL RELEVANCE STATEMENT: 2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery. KEY POINTS: • Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

Multi-shot Diffusion-Weighted MRI With Multiplexed Sensitivity Encoding (MUSE) in the Assessment of Active Inflammation in Crohn's Disease.

BACKGROUND: Single-shot diffusion-weighted imaging (ssDWI) has been shown useful for detecting active bowel inflammation in Crohn's disease (CD) without MRI contrast. However, ssDWI suffers from geometric distortion and low spatial resolution. PURPOSE: To compare conventional ssDWI with higher-resolution ssDWI (HR-ssDWI) and multi-shot DWI based on multiplexed sensitivity encoding (MUSE-DWI) for evaluating bowel inflammation in CD, using contrast-enhanced MR imaging (CE-MRI) as the reference standard. STUDY TYPE: Prospective. SUBJECTS: Eighty nine patients with histological diagnosis of CD from previous endoscopy (55 male/34 female, age: 17-69 years). FIELD STRENGTH/SEQUENCES: ssDWI (2.7 mm × 2.7 mm), HR-ssDWI (1.8 mm × 1.8 mm), MUSE-DWI (1.8 mm × 1.8 mm) based on echo-planar imaging, T2-weighted imaging, and CE-MRI sequences, all at 1.5 T. ASSESSMENT: Five raters independently evaluated the tissue texture conspicuity, geometry accuracy, minimization of artifacts, diagnostic confidence, and overall image quality using 5-point Likert scales. The diagnostic performance (sensitivity, specificity and accuracy) of each DWI sequences was assessed on per-bowel-segment basis. STATISTICAL TESTS: Inter-rater agreement for qualitative evaluation of each parameter was measured by the intra-class correlation coefficient (ICC). Paired Wilcoxon signed-rank tests were performed to evaluate the statistical significance of differences in qualitative scoring between DWI sequences. A P value <0.05 was considered to be statistically significant. RESULTS: Tissue texture conspicuity, geometric distortions, and overall image quality were significantly better for MUSE-DWI than for ssDWI and HR-ssDWI with good agreement among five raters (ICC: 0.70-0.89). HR-ssDWI showed significantly poorer performance to ssDWI and MUSE-DWI for all qualitative scores and had the worst diagnostic performance (sensitivity of 57.0% and accuracy of 87.3%, with 36 undiagnosable cases due to severe artifacts). MUSE-DWI showed significantly higher sensitivity (97.5% vs. 86.1%) and accuracy (98.9% vs. 95.1%) than ssDWI for detecting bowel inflammation. DATA CONCLUSION: MUSE-DWI was advantageous in assessing bowel inflammation in CD, resulting in improved spatial resolution and image quality. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Magnetic resonance imaging metrics and the predictability of adverse outcomes in on-treatment Asian chronic hepatitis B.

BACKGROUND AND AIM: Liver fibrosis and steatosis are important factors affecting chronic hepatitis B (CHB) disease outcome. Multiparametric magnetic resonance (MR) imaging of the liver measures fibroinflammation, fat, and iron through iron-corrected T1 relaxation time (cT1), proton density fat fraction (PDFF), and T2*-weighted imaging, respectively. We assessed the utility of MR metrics for prognostication in CHB. METHODS: Chronic hepatitis B patients receiving nucleos(t)ide analogs with advanced fibrosis documented by vibration-controlled transient elastography were recruited. Paired multiparametric MR liver and transient elastography were performed at baseline and after at least 2 years. Adverse outcomes including death, hepatocellular carcinoma (HCC), and liver decompensation were monitored. RESULTS: One hundred and ninety-two patients (mean age 60.3 ± 8.5 years; 76.0% male) were recruited. Eight patients (4.2%) developed HCC after 11.6 (8.8-22.8) months, and increased baseline liver iron independently predicted HCC (hazard ratio 2.329 [1.030-5.266]; P = 0.042). Liver MR metrics were not predictive of death or hepatic decompensation. Among 150 patients with follow-up liver MR at 30.3 (25.2-35.6) months, longitudinal liver PDFF increase was associated with liver cT1 increase (odds ratio 1.571 [1.217-2.029]; P = 0.001). Ninety patients received simultaneous multiparametric MR pancreas during the follow-up MR. Pancreatic PDFF correlated with liver PDFF (r = 0.501, P < 0.001), while pancreatic T1 had no correlation with liver cT1 (r = -0.092, P = 0.479). Pancreatic T1 and PDFF were not associated with adverse outcomes. CONCLUSION: Among CHB patients with advanced disease, liver iron level on MR predicts HCC. Multiparametric MR can also simultaneously assess the pancreas and the liver. Multiparametric MR should be further studied as a one-stop option for monitoring and prognosticating CHB.

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.

Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19.

Background Current coronavirus disease 2019 (COVID-19) radiologic literature is dominated by CT, and a detailed description of chest radiography appearances in relation to the disease time course is lacking. Purpose To describe the time course and severity of findings of COVID-19 at chest radiography and correlate these with real-time reverse transcription polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, nucleic acid. Materials and Methods This is a retrospective study of patients with COVID-19 confirmed by using RT-PCR and chest radiographic examinations who were admitted across four hospitals and evaluated between January and March 2020. Baseline and serial chest radiographs (n = 255) were reviewed with RT-PCR. Correlation with concurrent CT examinations (n = 28) was performed when available. Two radiologists scored each chest radiograph in consensus for consolidation, ground-glass opacity, location, and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. Results The study was composed of 64 patients (26 men; mean age, 56 years ± 19 [standard deviation]). Of these, 58 patients had initial positive findings with RT-PCR (91%; 95% confidence interval: 81%, 96%), 44 patients had abnormal findings at baseline chest radiography (69%; 95% confidence interval: 56%, 80%), and 38 patients had initial positive findings with RT-PCR testing and abnormal findings at baseline chest radiography (59%; 95% confidence interval: 46%, 71%). Six patients (9%) showed abnormalities at chest radiography before eventually testing positive for COVID-19 with RT-PCR. Sensitivity of initial RT-PCR (91%; 95% confidence interval: 83%, 97%) was higher than that of baseline chest radiography (69%; 95% confidence interval: 56%, 80%) (P = .009). Radiographic recovery (mean, 6 days ± 5) and virologic recovery (mean, 8 days ± 6) were not significantly different (P = .33). Consolidation was the most common finding (30 of 64; 47%) followed by ground-glass opacities (21 of 64; 33%). Abnormalities at chest radiography had a peripheral distribution (26 of 64; 41%) and lower zone distribution (32 of 64; 50%) with bilateral involvement (32 of 64; 50%). Pleural effusion was uncommon (two of 64; 3%). The severity of findings at chest radiography peaked at 10-12 days from the date of symptom onset. Conclusion Findings at chest radiography in patients with coronavirus disease 2019 frequently showed bilateral lower zone consolidation, which peaked at 10-12 days from symptom onset. © RSNA, 2020.

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.

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.

Role of second high-intensity focused ultrasound (HIFU) treatment for unsatisfactory benign thyroid nodules after first treatment.

BACKGROUND: We aimed to assess the efficacy and safety of second high-intensity focused ultrasound (HIFU) ablation treatment in benign thyroid nodules that had failed to shrink by > 50% 6 months after the first treatment. METHODS: Twenty-eight patients who did not achieve 50% volume reduction at 6 months after the first HIFU treatment underwent a second HIFU treatment. Nodule volume was measured on ultrasound at baseline, 3 months and 6 months. Extent of nodule shrinkage (by volume reduction ratio) (VRR) = [Baseline volume - volume at 6 months]/[Baseline volume] * 100. Treatment success was defined as VRR > 50%. Obstructive symptom score (by 0-10 visual analogue scale, VAS) was evaluated for 6 months after treatment. RESULTS: No complications occurred after the second treatment. The mean 6-month VRR was 21.78 ± 16.87% with a median (range) of 16.16 (1.63-54.07)%. At 6 months, only two (7.1%) patients achieved treatment success, while nine (32.1%) patients had VRR < 10%. However, relative to baseline (3.96 ± 1.04), the mean VAS significantly improved at 3 and 6 months (2.96 ± 1.43, p<0.001 and 2.58 ± 1.39, p<0.001, respectively). There was a significant correlation between VRR and improvement in VAS score at 6 months (ρ=0.438, p=0.025). Greater nodule volume before the second treatment (OR=1.169, 95% CI=1.004-1.361, p=0.045) was a significant factor for greater VRR after the second treatment. CONCLUSIONS: Although subjective obstructive symptoms continued to improve after the second treatment, the actual extent of nodule shrinkage was small. Larger-volume nodules tended to shrink more significantly than smaller-volume nodules in the second treatment. KEY POINTS: • Second treatment resulted in small shrinkage in unsatisfactory nodules after first treatment. • Obstructive symptoms tended to continue to improve after second treatment. • Larger-size nodules tended to respond better in the second treatment.

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.

Two-year outcomes of single-session high-intensity focused ultrasound (HIFU) treatment in persistent or relapsed Graves' disease.

OBJECTIVE: To evaluate the longer-term disease relapse of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) ablation as a treatment for persistent/relapsed Graves' disease (GD). METHODS: After ethics approval, consecutive patients with persistent or relapsed GD who underwent bilateral US-guided HIFU ablation from 2016 to 2017 were retrospectively analyzed. Altogether, 75 patients received HIFU ablation of the central portion of the right and left thyroid lobes with areas near the trachea-esophageal groove and common carotid artery un-ablated. They were followed for 24 months or longer. Baseline thyrotropin (TSH), free T4, anti-thyroid autoantibodies, and TSH receptor (TSHR) antibody were checked. Primary outcome was the 24-month relapse rate. Relapse referred to hyperthyroidism (free T4 (FT4) > 23 pmol/L) afterwards. Variables associated with relapse were analyzed by binary logistic regression. RESULTS: The cohort comprised mostly females (84.0%) with a mean age of 42.05 ± 10.74 years. The 24-month relapse rate was 41.3% with 31 patients suffering a relapse. No patient suffered from hypothyroidism. Three patients (4.0%) suffered from temporary vocal cord palsy but these injuries recovered spontaneously after 2 months. In univariate analysis, higher daily dose of carbimazole (OR = 1.125, 95% CI = 1.023-1.237, p = 0.015) and higher baseline TSHR level (OR = 1.085, 95% CI = 1.022-1.152, p = 0.007) were significant factors for disease relapse. In the multivariate analysis, higher baseline TSHR level was a significant independent factor for disease relapse within 24 months (OR = 1.079, 95% CI = 1.014-1.148, p = 0.016). CONCLUSIONS: US-guided HIFU of the thyroid gland was a safe and relatively efficacious treatment in the longer term for patients with persistent or relapsed GD. KEY POINTS: • US-guided HIFU ablation is relatively efficacious in the longer term. • US-guided HIFU ablation of the thyroid is safe. • Higher TSHR level may lead to higher disease relapse after treatment.

High intensity focused ultrasound (HIFU) ablation of benign thyroid nodule is safe and efficacious in patients who continue taking an anti-coagulation or anti-platelet agent in the treatment period.

BACKGROUND: High intensity focused ultrasound (HIFU) ablation is a promising treatment for benign thyroid nodules but because bleeding complications can occur following any intervention to the thyroid gland, the safety and efficacy of HIFU ablation were evaluated in patients who continued taking an anti-coagulation or anti-platelet agent during treatment. METHODS: From 2015 to 2017, 303 patients who underwent a single-session ablation for a benign thyroid nodule were analyzed. The primary study endpoint was thyroid bleeding, intra-lesional or peri-thyroidal hematoma or neck bruising diagnosed within 4 days of the treatment. Other endpoints included treatment-related complications, extent of nodule shrinkage and symptom score. Nodule volume was estimated by ultrasound. Extent of nodule shrinkage (by volume reduction ratio) (VRR)= [Baseline volume - volume at 6-month]/[Baseline volume] × 100. Obstructive symptom score (by 0- 10 visual analog scale, VAS) was evaluated after treatment. RESULTS: Twelve patients continued taking an anti-coagulation or anti-platelet agent while the other 291 patients did not during treatment. No patients in either group suffered active thyroid bleeding, intralesional/pericapsular hematoma or subcutaneous neck bruising in the first 4 days of treatment. Complication rate and the 6-month VRR were comparable between the two groups (0.0% vs. 1.7%, p = 1.000 and 55.96% vs. 61.29%, respectively, p = .073). CONCLUSIONS: HIFU ablation is a feasible treatment in patients who continue to take an anti-coagulation or anti-platelet agent during treatment and might be preferable in patients who continuously require an anti-coagulation or anti-platelet agent for one reason or another during treatment.

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.

Single-Session High-Intensity Focused Ultrasound Treatment for Persistent or Relapsed Graves Disease: Preliminary Experience in a Prospective Study.

Purpose To evaluate the safety and efficacy of ultrasonography (US)-guided high-intensity focused ultrasound (HIFU) ablation as a treatment for medically refractory Graves disease (GD). Materials and Methods After ethics approval, a prospective trial (NCT02685514) was performed from November 2015 to February 2016. Thirty patients underwent ablation of the entire right and left thyroid lobes, with areas near the tracheal-esophageal groove and common carotid artery left unablated. Serum thyroid-stimulating hormone (TSH), free T4 (FT4), antithyroid autoantibodies, and TSH receptor (TSHR) antibody levels were evaluated afterward, and US color Doppler, US volumetry, and eye assessment were performed. The primary outcome was the 12-month relapse rate. Relapse referred to hyperthyroidism (FT4 > 23 pmol/L) afterward. Variables associated with relapse were analyzed by using binary logistic regression. Results The technical success rate was 96.7%. The cohort comprised entirely women, with a median age of 38.2 years (interquartile range, 29.5-49.0 years). After 12 months, eight patients (26.7%; 95% confidence interval [CI]: 14.19%, 44.95%) experienced relapse. One patient (3.3%; 95% CI: 0.59%, 16.67%) experienced vocal cord palsy, while two patients (6.7%; 95% CI: 1.85%, 21.33%) experienced Horner syndrome, but none of these conditions were permanent. No changes in gland volume, antithyroid autoantibody levels, and ophthalmic parameters were found at 12-month follow-up. Baseline TSHR was found to have decreased significantly at 6- and 12-month follow-up (P < .001 for both). TSHR antibody (odds ratio [OR] = 1.414; 95% CI: 1.018, 1.965; P = .039) and gland volume (OR = 0.557; 95% CI: 0.353, 0.880; P = .012) were associated with 12-month relapse, with higher antibody levels conferring a higher likelihood and smaller gland volumes conferring a lower likelihood. Conclusion US-guided HIFU of the thyroid may be a safe and efficacious treatment in patients with persistent or relapsed GD. However, further study is warranted before it can become mainstream for this indication. © RSNA, 2017 Online supplemental material is available for this article.

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.

Vocal cord paresis following single-session high intensity focused ablation (HIFU) treatment of benign thyroid nodules: incidence and risk factors.

BACKGROUND: Vocal cord paresis (VCP) may occur following high intensity focused ultrasound (HIFU) of thyroid nodules. We hypothesised its occurrence relates to the distance of the focus point (FP) of the HIFU beams from the recurrent laryngeal nerve (RLN) and the thermal power that this point received. Their relationships were examined. METHODS: One hundred and three patients who underwent HIFU for symptomatic benign thyroid nodule from October 2015 to March 2017 were analysed. All treatment images were captured and were later watched by 2 reviewers to identify three FPs closest to the tracheoesophageal groove (TEG) on transverse sonographic view. TEG was taken as the RLN position. After identifying these FPs, their distance (mm) from the TEG, thermal power (W) used and depth from skin (mm) were recorded. These parameters were compared between those with and without VCP. VCP was defined as a cord with reduced or no movement. RESULTS: Four (3.9%) patients suffered from a unilateral VCP afterwards but they all recovered fully within 6 weeks. There were no significant differences in baseline characteristics and treatment efficacy between the two groups. The distance from TEG (OR = 1.706, 95%CI = 1.001 to 2.915, p = 0.050) was the only significant factor for VCP. None of the other variables including thermal power were significant. CONCLUSIONS: The incidence of VCP was 3.9% (4/103) and they completely recovered within 6 weeks. The distance between the FP and the TEG was the only related factor for VCP. The safe distance between FP and TEG should be ≥1.1 cm.

Prognostic PET [11C]-acetate uptake is associated with hypoxia gene expression in patients with late-stage hepatocellular carcinoma - a bench to bed study.

BACKGROUND: Positron Emission Tomography (PET) with combined [18F]-FDG and [11C]-acetate (dual-tracer) is used for the management of hepatocellular carcinoma (HCC) patients, although its prognostic value and underlying molecular mechanism remain poorly understood. We hypothesized that radiotracer uptake might be associated with tumor hypoxia and validated our findings in public and local human HCC cohorts. METHODS: Twelve orthotopic HCC xenografts were established using MHCC97L cells in female nude mice, with 5 having undergone hepatic artery ligation (HAL) to create tumor hypoxia in vivo. Tumors in both Control and HAL-treated xenografts were imaged with [11C]-acetate and [18F]-FDG PET-MR and RNA sequencing was performed on the resected tumors. Semiquantitative analysis of PET findings was then performed, and the findings were then validated on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and patients from our institution. RESULTS: HAL-treated mice showed lower [11C]-acetate (HAL-treated vs. Control, tumor-to-liver SUV ratio (SUVTLR): 2.14[2.05-2.21] vs 3.11[2.75-5.43], p = 0.02) but not [18F]-FDG (HAL-treated vs. Control, SUVTLR: 3.73[3.12-4.35] vs 3.86[3.7-5.29], p = 0.83) tumor uptakes. Gene expression analysis showed the PET phenotype is associated with upregulation of hallmark hypoxia signature. The prognostic value of the hypoxia gene signature was tested on the TCGA-LIHC cohort with upregulation of hypoxia gene signature associated with poorer overall survival (OS) in late-stage (stage III and IV) HCC patients (n = 66, OS 2.05 vs 1.67 years, p = 0.046). Using a local cohort of late-stage HCC patients who underwent dual-tracer PET-CT, tumors without [11C]-acetate uptake are associated with poorer prognosis (n = 51, OS 0.25 versus 1.21 years, p < 0.0001) and multivariable analyses showed [11C]-acetate tumor uptake as an independent predictor of OS (HR 0.17 95%C 0.06-0.42, p < 0.0001). CONCLUSIONS: [11C]-acetate uptake is associated with alteration of tumor hypoxia gene expression and poorer prognosis in patients with advanced HCC.