Long-term efficacy of microwave ablation for multifocal papillary thyroid microcarcinoma: a 5-year follow-up study.

OBJECTIVES: Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines. METHODS: This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery. RESULTS: After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period. CONCLUSIONS: Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS). CLINICAL RELEVANCE STATEMENT: This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance. KEY POINTS: • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.

Incorporation of CEUS and SWE parameters into a multivariate logistic regression model for the differential diagnosis of benign and malignant TI-RADS 4 thyroid nodules.

PURPOSE: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) quantitative analysis parameters combined with shear wave elastography (SWE) quantitative parameters in the differentiation of benign and malignant ACR TI-RADS category 4 thyroid nodules and to provide a more effective reference for clinical work. METHODS: We analyzed 187 category 4 nodules, including 132 nodules in the development cohort and 55 nodules in the validation cohort, divided the development cohort into benign and malignant groups, and analyzed the differences in all CEUS and SWE quantitative parameters between the two groups. We selected the highest AUC of the two parameters, performed binary logistic regression analysis with the ACR TI-RADS score and constructed a diagnostic model. ROC curves were applied to evaluate their diagnostic efficacy. RESULTS: 1) The diagnostic model had an AUC of 0.926, sensitivity of 87.5%, specificity of 86.8%, diagnostic threshold of 3, accuracy of 87.12%, positive predictive value of 86.15%, and negative predictive value of 88.06%. 2) The diagnostic model had an AUC of 0.890 in the validation cohort, sensitivity of 81.5%, specificity of 79.6%, and accuracy of 80.00%. CONCLUSION: The combined multiparameter construction of the nodule diagnostic model can effectively improve the diagnostic efficacy of 4 types of thyroid nodules and provide a new reference index for clinical diagnostic work.

Endogenous H2O2 Self-Replenishment and Sustainable Cascades Enhance the Efficacy of Sonodynamic Therapy.

Purpose: Sonodynamic therapy (SDT), with its high tissue penetration and noninvasive advantages, represents an emerging approach to eradicating solid tumors. However, the outcomes of SDT are typically hampered by the low oxygen content and immunosuppression in the tumor microenvironment (TME). Accordingly, we constructed a cascade nanoplatform to regulate the TME and improve the anti-tumor efficiency of SDT. Methods: In this study, we rationally design cascade nanoplatform by incorporating immunostimulant hyaluronic acid (HA) and sonosensitizer chlorin e6 (Ce6) on the polydopamine nanocarrier that is pre-doped with platinum nanozymes (designated Ce6/Pt@PDA-HA, PPCH). Results: The cascade reactions of PPCH are evidenced by the results that HA exhibits reversing immunosuppressive that converts M2 macrophages into M1 macrophages in situ, while producing H2O2, and then platinum nanozymes further catalyze the H2O2 to produce O2, and O2 produces abundant singlet oxygen (1O2) under the action of Ce6 and low-intensity focused ultrasound (LIFU), resulting in a domino effect and further amplifying the efficacy of SDT. Due to its pH responsiveness and mitochondrial targeting, PPCH effectively accumulates in tumor cells. Under LIFU irradiation, PPCH effectively reverses immunosuppression, alleviates hypoxia in the TME, enhances reactive oxygen species (ROS) generation, and enhances SDT efficacy for eliminating tumor cells in vivo and in vitro. Meanwhile, an in vivo dual-modal imaging including fluorescence and photoacoustic imaging achieves precise tumor diagnosis. Conclusion: This cascade nanoplatform will provide a promising strategy for enhancing SDT eradication against tumors by modulating immunosuppression and relieving hypoxia.

Nomogram prediction for cervical lymph node metastasis in multifocal papillary thyroid microcarcinoma.

Aim: Accurate preoperative prediction of cervical lymph node metastasis (LNM) in patients with mPTMC provides a basis for surgical decision making and the extent of tumor resection. This study aimed to develop and validate an ultrasound radiomics nomogram for the preoperative assessment of LN status. Methods: A total of 450 patients pathologically diagnosed with mPTMC were enrolled, including 348 patients in the modeling group and 102 patients in the validation group. Univariate and multivariate logistic regression analyses were performed on the basic information, ultrasound characteristics, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) scores of the patients in the modeling group to identify independent risk factors for LNM in mPTMC and to construct a logistic regression equation and nomogram to predict the risk of LNM. The validation group data were used to evaluate the predictive performance of the nomogram. Results: Male sex, age <40 years, a single lesion with a maximum diameter >0.5 cm, capsular invasion, a maximum ACR score >9 points, and a total ACR score >19 points were independent risk factors for the development of cervical LNM in mPTMC. Both the area under the curve (AUC) and concordance index (C-index) of the prediction model constructed from the above six factors were 0.838. The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, decision curve analysis (DCA) demonstrated a significantly greater net benefit of the model. The external validation demonstrated the reliability of the prediction nomogram. Conclusions: The presented radiomics nomogram, which is based on ACR TI-RADS scores, shows favorable predictive value for the preoperative assessment of LNs in patients with mPTMC. These findings may provide a basis for surgical decision making and the extent of tumor resection.

Study on Changes in Immune Function After Microwave Ablation of Papillary Thyroid Microcarcinoma.

Background: In recent years, papillary thyroid microcarcinoma (PTMC) has been a main cause of the high incidence of thyroid carcinoma. No existing study has reported whether microwave ablation (MWA) affects patients' immunity. Therefore, this study explored the effects of MWA treatment on the immune functions of patients with PTMC. Methods: This study included 50 patients diagnosed with PTMC who received MWA treatment under ultrasound guidance at the ultrasound department of our hospital from January 2019 to October 2020. Changes in immune function after MWA treatment in PTMC patients were detected by T lymphocyte subsets and cytokines secreted by T helper cells. Results: At 1 day and 2 weeks after MWA treatment, the proportions of CD3+, CD4+ and CD4+/CD8+ T lymphocyte subsets and the levels of the cytokines interleukin (IL)-2 and interferon (IFN)-γ in the peripheral blood of the patients were significantly higher than those before MWA treatment (P<0.05). The levels of CD8+ T lymphocytes, tumour necrosis factor (TNF)-α, IL-4, IL-6, IL-10 and IL-17A were not significantly different from those before MWA treatment (P>0.05). One month after MWA treatment, the proportions of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocytes and the levels of the cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17A were not significantly different from those before MWA treatment (P>0.05). Conclusion: The immune functions of patients with PTMC are temporarily enhanced after MWA treatment, which has important clinical significance for patients' anti-PTMC ability.

Long-term outcome of microwave ablation for benign thyroid nodules: Over 48-month follow-up study.

Objectives: The short-term effects of microwave ablation (MWA) for the treatment of benign thyroid nodules (BTNs) were satisfactory in previous studies. However, as a slowly progressing disease, the long-term efficacy of MWA for BTNs at present is not clear. Our study aim was to assess the long-term results of MWA for BTNs after a 48-month follow-up. Methods: From June 2015 to September 2017, 148 patients had 148 BTNs. All patients were from the China-Japan Union Hospital of Jilin University. Careful ultrasound examinations were performed 1 day, 1 month, 3 months, 6 months, 12 months, and every 6 months after MWA. The volume, volume reduction rate (VRR), recurrence rate of the ablated area and thyroid function were recorded. Results: The mean volumes of the 148 nodules were 15.6 ± 9.4 cm3 (range: 1.3-48.9 cm3) and 0.6 ± 0.6 cm3 (range: 0-3.5 cm3) before and 48 months after MWA, respectively, with a nodule VRR of 96.9 ± 2.5% (range: 90.4-100%). Two patients (1.35%) had recurrence after MWA. Compared with thyroid function before MWA, no significant variation was observed after MWA. Five patients experienced complications (3.38%): two patients (1.35%) had bleeding, two patients (1.35%) had ear pain and toothache during MWA, and one patient (0.68%) had hoarseness after MWA. No cases of oesophageal injury, tracheal injury, infection, skin burns, etc., were reported during or after MWA. Conclusions: Based on a long-term follow-up, MWA is an effective method for treating BTNs and is expected to be a potential first-line treatment.

The efficacy and safety of microwave ablation versus lobectomy for the treatment of benign thyroid nodules greater than 4 cm.

PURPOSE: To evaluate the safety and effectiveness of microwave ablation (MWA) versus lobectomy for the treatment of benign thyroid nodules > 4 cm. METHODS: We retrospectively analyzed the data of 48 patients who underwent MWA and 53 patients who underwent lobectomy to treat benign thyroid nodules > 4 cm. The patients were followed up for 12 months. The volume reduction ratio (VRR) was calculated. The operation time, incision length, hospitalization time, complications, thyroid function, symptoms, and cosmetic improvement were analyzed and compared between the two groups. RESULTS: During the 12-month follow-up, the mean nodule volume in the MWA group was reduced from 36.1 ± 23.1 to 4.0 ± 4.1 ml, and the mean VRR of the nodules was 90 ± 5% in the MWA group, which was comparable with that in the surgery group. No significant postoperative change in thyroid function was observed in the MWA group. Compared with the surgery group, the incidence of complications and postoperative pain in the MWA group were lower, the operation time, incision length, and hospitalization time in the MWA group were shorter, and satisfaction with the esthetic results in the MWA group was greater. CONCLUSION: MWA is safe and effective for the treatment of benign thyroid nodules > 4 cm. Moreover, MWA is associated with a faster recovery, fewer complications, better protection of thyroid function, and superior esthetic results relative to thyroid lobectomy.

Comparison of ultrasound-guided thermal ablation and conventional thyroidectomy for benign thyroid nodules: a systematic review and meta-analysis.

Objective: To compare the safety and efficacy of ultrasound-guided thermal ablation and conventional thyroidectomy for benign thyroid nodules (TNs) by performing a systematic review and meta-analysis.Methods: We searched PubMed, Embase, Web of Science and Cochrane Library databases for clinical trials from the date of their inception to 1 April 2019. Two investigators independently examined the trials to select qualified studies, extracted relevant information and assessed the risk of bias according to the Cochrane Collaboration checklist (Oxford, UK). The primary study outcomes were safety (hoarseness, hypothyroidism and postoperative pain) and efficacy (symptom improvement, postoperative cosmetic effects and hospitalization time). This study is registered with PROSPERO (CRD42019125643).Results: Seven studies involving 1289 patients were included. The results demonstrated that the incidences of hoarseness [odds ratio (OR) 0.33, 95% confidence interval (95% CI) (0.14, 0.79)], hypothyroidism [risk difference (RD) -0.31, 95% CI (-0.34, -0.28)] and postoperative pain [OR 0.35, 95% CI (0.25, 0.49)] were lower, and the hospitalization time was shorter [standard mean difference (SMD) -4.01, 95% CI (-4.22, -3.81)], in the thermal ablation group than in the conventional thyroidectomy group, and postoperative cosmetic effects were better [relative risk (RR) ratio 1.12, 95% CI (1.01, 1.24)] (p < 0.05). For symptom improvement, the difference was not statistically significant.Conclusions: This study shows that for benign TNs, ultrasound-guided thermal ablation may have potential advantages in terms of safety, cosmetic effects and shorter hospitalization time compared with conventional thyroidectomy, while symptom improvement is the same.

Effects of Microwave Ablation on Papillary Thyroid Microcarcinoma: A Five-Year Follow-Up Report.

Background: Some researchers have achieved favorable efficacy in the treatment of primary papillary thyroid microcarcinoma (PTMC) using microwave ablation (MWA). However, as PTMC is a slowly progressing disease, a long follow-up period is required to confirm treatment efficacy. Our study aim was to investigate the long-term efficacy and safety of ultrasound (US)-guided MWA in PTMC. Methods: In this study, 41 patients with thyroid masses (41 nodules) were diagnosed with PTMC by fine-needle aspiration or core needle biopsy. They underwent US-guided MWA. Preablation ultrasonic images of the thyroid nodules were collected, and the volumes were measured. The patients had follow-up at 1, 3, 6, and 12 months in the first year and every 6 months from the second year on, after MWA. The volume reduction rates (VRRs) of the thyroid nodules were analyzed. Results: In total, 40 of 41 nodules were completely ablated by MWA. After 60 months of follow-up, the volume significantly decreased from a median of 55.78 mm3 (quartile: 21.50, 112.20 mm3) to 0 mm3 (0, 0 mm3) (p < 0.001), with a VRR of 99.37% ± 4.02%. Two patients developed hoarseness after ablation; one recovered within 10 minutes, and the hoarseness in the other patient resolved 2 months after the ablation. No recurrence, metastatic cervical lymph nodes, or distal metastasis was found during the follow-up period. Conclusions: In this five-year follow-up, MWA presented favorable efficacy with satisfactory safety for the treatment of PTMC. It should be considered an alternative therapy to surgery and active surveillance for solitary PTMC.

Comparison and preliminary discussion of the reasons for the differences in diagnostic performance and unnecessary FNA biopsies between the ACR TIRADS and 2015 ATA guidelines.

OBJECTIVES: (1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules <1 cm in diameter. MATERIALS AND METHODS: In the present study, 1000 thyroid nodules in 894 consecutive patients with final diagnoses were included; these thyroid nodules were investigated via FNA biopsies in our hospital. The ultrasound (US) features of the thyroid nodules were reviewed and stratified according to the categories defined by the ACR TIRADS and ATA guidelines. RESULTS: Compared with the ACR TIRADS guidelines, the ATA guidelines had a higher sensitivity (93.4% (P < 0.001)) and a larger negative predictive value (NPV) (85.3% (P= 0.034)). Compared with the ATA guidelines, the ACR TIRADS guidelines had a higher specificity (66.0% (P < 0.001)), a greater PPV (73.6% (P= 0.001)), and greater accuracy (75.5% (P= 0.017)). Compared with the ATA guidelines, the ACR TIRADS guidelines resulted in significantly fewer unnecessary FNA biopsies (P= 0.007). CONCLUSIONS: This study suggests that both the ACR TIRADS and ATA guidelines have unique strengths with regard to their diagnostic performance. In terms of reducing the number of FNA biopsies, the ACR TIRADS guidelines were superior to the ATA guidelines.

Elevated interleukin-35 suppresses liver inflammation by regulation of T helper 17 cells in acute hepatitis B virus infection.

Interleukin (IL)-35 is a responsive anti-inflammatory cytokine implicated in different diseases processes. It has been reported that elevated IL-35 contributed to immunosuppression in chronic hepatitis by modulation of T helper 17 (Th17) and regulatory T cells. However, the role of IL-35 in acute hepatitis B (AHB) was still not completely elucidated. Thus, in the present study, we analyzed the expression and regulatory activity of IL-35 to Th17 cells and inflammatory response during acute hepatitis B virus (HBV) infection in both peripheral blood cells isolated from AHB patients and in hydrodynamic induced HBV-infected mouse model. Plasma IL-35 level and circulating HBV peptides-induced Th17 frequency was significantly elevated in AHB patients, and IL-35 expression negatively correlated with liver inflammation. In vitro IL-35 stimulation to CD4+ T cells purified from AHB patients down-regulated HBV peptides-induced Th17-phenotype, which presented as reduced IL-17 and IL-22 production. In vivo IL-35 administration dampened liver inflammation in HBV plasmid injected mice, however, did not affect HBV antigens production. This process was accompanied by suppression of natural killer cells and down-regulation of HBV peptides-induced Th17 cells in the liver, but did not affect total intrahepatic lymphocytes and other cell subsets numbers or chemokines expression in the liver. In conclusion, the current data indicated that IL-35 might be a novel mediator associated with hepatocytes damage and liver inflammation by regulating HBV peptides-induced Th17 cells during acute HBV infection. The potential anti-inflammatory property of IL-35 might be pivotal for developing new therapeutic approaches for hepatitis B.

Preliminary report of microwave ablation for the primary papillary thyroid microcarcinoma: a large-cohort of 185 patients feasibility study.

PURPOSE: To assess the safety and efficacy of microwave ablation (MWA) for primary papillary thyroid microcarcinoma (PTMC) with a large sample of 185 patients. METHODS: A total of 185 patients underwent MWA for 206 primary PTMC nodules. They received ultrasound follow-up at 1, 3, 6, and 12 months after MWA and every 6 months thereafter. Nodule volumes were calculated at each follow-up and compared with those before MWA. Additionally, the volume reduction rate (VRR) of the nodules was calculated. Patients' thyroid functions were tested before and 1 month after MWA. RESULTS: The mean follow-up time of the 185 patients was 20.7 ± 8.8 months (range 12-36 months). During the follow-up period, the mean volume of the 206 nodules was 100.1 ± 92.9 mm3 (range 3.6-423.9) before MWA, which decreased to 2.2 ± 5.6 mm3 (range 0-20.3 mm3) after MWA (P = 0.000). The mean VRR of the nodules was 98.65 ± 3.60% after MWA (range 83.85-100%). One hundred and seventy four of 206 nodules (84.5%) were fully absorbed. Compared with the preoperative results, no significant variation in thyroid function was observed 1 month after MWA. Thirty-eight patients (20.5%) had different types of complications, ranging from minor to major. Five patients (2.7%) had hoarseness, 11 patients (5.9%) had bleeding, 21 patients (11.4%) had earache or toothache, and one patient had another lesion 1 month after MWA. CONCLUSIONS: This preliminary study suggests that MWA is safe and effective in the treatment of primary PTMC and offers a new alternative for clinical treatment.

Value of ultrasound elastography in assessment of enlarged cervical lymph nodes.

BACKGROUND: To investigate the value of ultrasound elastography (UE) in the differentiation between benign and malignant enlarged cervical lymph nodes (LNs). METHODS: B-mode ultrasound, power Doppler imaging and UE were examined to determine LN characteristics. Two kinds of methods, 4 scores of elastographic classification and a strain ratio (SR) were used to evaluate the ultrasound elastograms. RESULTS: The cutoff point of SR had high utility in differential diagnosis of benign and malignant of cervical lymph nodes, with good sensitivity, specificity and accuracy. CONCLUSION: UE is an important aid in differential diagnosis of benign and malignant cervical LNs.