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.

Recent advances in sonodynamic immunotherapy.

Tumor immunotherapy has become an important means of tumor therapy by enhancing the immune response and triggering the activation of immune cells. However, currently, only a small number of patients respond to immunotherapy alone, and patients may experience immune-related adverse events (irAEs) during the course of treatment. Sonodynamic therapy (SDT) can produce cytotoxic substances to tumor tissue, induce apoptosis and enhance immunity. SDT combined with immunotherapy is considered a promising strategy for cancer treatment. In this mini review, we summarize the role of SDT in immunotherapy in recent years, including the application of SDT-triggered immunotherapy and the combination of SDT and immunotherapy.

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.

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 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.

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.

MicroRNA-338-3p inhibits thyroid cancer progression through targeting AKT3.

microRNA-338-3p (miR-338-3p) has been implicated in tumor development and progression in many types of cancers. However, the function and mechanism underlying the action of miR-383-3p in thyroid cancer remain unclear and were therefore investigated in this study by in vitro and in vivo experiments. We found that miR-338-3p was downregulated in thyroid cancer tissues and cell lines. miR-338-3p expression was significantly associated with the clinical stage and lymph node metastasis of thyroid cancer. Forced expression of miR-338-3p suppressed thyroid cancer cell proliferation, clonogenicity, migration, and invasion in vitro and inhibited tumorigenesis in a nude mouse xenograft model system. Moreover, AKT3, a known oncogene, was confirmed as a direct target of miR-383-3p in thyroid cancer cells, as evidenced by the fact that ectopic miR-383 expression suppressed AKT3 expression and its downstream pathway (AKT pathway). In addition, AKT3 silencing by siRNA mimicked the effect of ectopic miR-338-3p on the growth and invasion of thyroid cancer cells. In contrast, AKT3 overexpression attenuated the inhibitory effect induced by miR-338-3p overexpression in thyroid cancer cells. These results suggest that miR-338-3p functions as a novel tumor suppressor that blocks thyroid cancer cell growth through targeting AKT3.

The value of combined application of ultrasound-guided fine needle aspiration cytology and thyroglobulin measurement for the diagnosis of cervical lymph node metastases from thyroid cancer.

OBJECTIVE: The aim of this study was to explore the diagnostic value of ultrasound-guided (US-guided) fine-needle aspiration cytology (FNAC), thyroglobulin measurement on fine-needle aspiration (FNA-Tg), combined US-guided FNAC, and the ratio between FNA-Tg and serum Tg (FNA-Tg/serum Tg) for patients with cervical lymph node (CLN) metastases from thyroid carcinoma. METHODS: We selected 148 patients with thyroid cancer with suspicious CLN metastases who met the inclusion criteria. FNAC findings, FNA-Tg levels, and serum Tg levels were evaluated before surgical treatment. The results of FNAC and FNA-Tg from CLNs were analyzed retrospectively. RESULTS: Ninety-four of 148 cases were metastatic and 54 were benign. The sensitivity, specificity, and accuracy of FNAC were 68.1%, 100.0%, and 79.7%, respectively. The sensitivity, specificity, and accuracy of FNA-Tg/serum Tg were 91.5%, 88.9%, and 90.5%, respectively. The sensitivity, specificity, and accuracy of FNA-Tg [10 ng/mL] were 98.9%, 68.5%, and 87.8%, respectively. The sensitivity, specificity, and accuracy of combined US-guided FNAC and FNA-Tg/serum Tg were 95.7%, 96.3%, and 95.9%, respectively. There was a statistically significant difference between FNAC and combined US-guided FNAC and FNA-Tg/serum Tg for sensitivity, specificity, and accuracy (P < 0.05). CONCLUSION: The method of FNA-Tg/serum Tg is sensitive enough for diagnosing CLN metastases from thyroid cancer. The combined application of US-guided FNAC and FNA-Tg/serum Tg contributes to improving the accuracy of diagnosing CLN metastases in patients with thyroid cancer.

Comparison of strain ratio with elastography score system in differentiating malignant from benign thyroid nodules.

BACKGROUND: To prospectively compare strain ratio to elastography score system in distinguishing between malignant and benign thyroid nodules. METHODS: The local institutional review board approved the study, and all patients provided written informed consent. We examined 168 thyroid nodules (52 malignant and 116 benign) with freehand elastography. The elastogram was performed with both the five-degree elastography score system and thyroid tissue-to-nodule strain ratio before core biopsies as standard reference. The area under the curve (AUC) and the best cut-off point were both obtained using receiver-operating characteristic (ROC) curve analysis. The sensitivity, specificity, and accuracy of both techniques were compared with the χ(2) test. Furthermore, strain ratio distribution was also compared with histopathological result. P<.05 was considered to indicate significance. RESULTS: The strain ratio distribution of malignant thyroid nodules significantly differed from that of benign nodules (all P<.001). The AUC of strain ratio was higher than that of the elastography score system (0.907 vs. 0.829; P<.05). By applying the best cut-off point of 3.855 for strain ratio and 3.5 for the elastography score system, strain ratio had significantly higher specificity (P<.05) in detecting malignant thyroid nodules. However, there was no significant difference in the sensitivity in distinguishing malignant thyroid nodules from benign ones between strain ratio and the elastography score system (P>.05). CONCLUSION: Strain ratio is more specific than conventional elastography score system in differentiating malignant from benign thyroid nodules.

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.