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.

Multifunctional Phase-Transition Nanoparticles for Effective Targeted Sonodynamic-Gene Therapy Against Thyroid Papillary Carcinoma.

Introduction: In order to diagnose and treat papillary thyroid carcinoma (PTC) accurately, phase-transition nanoparticles, P@IP-miRNA (PFP@IR780/PLGA-bPEI-miRNA338-3p), was engineered. The nanoparticles (NPs) can target the tumor cells, realize the multimodal imaging, and provide sonodynamic-gene therapy for PTC. Methods: P@IP-miRNA NPs were synthesized through double emulsification method, and miRNA338-3p was attached to the surface of the NPs by electrostatic adsorption. The characterization of NPs was detected to screen out qualified nanoparticles. In vitro, laser confocal microscopy and flow cytometry were used to detect the targeting and subcellular localization of NPs. Western blot, qRT-PCR, and immunofluorescence were used to detect the ability to transfect miRNA. CCK8 kit, laser confocal microscopy and flow cytometry were used to detect the inhibition on TPC-1 cells. In vivo experiments were performed based on tumor-bearing nude mice. The efficacy of combined treatment by NPs was comprehensively evaluated, and the multimodal imaging ability of NPs in vivo and in vitro was detected. Results: P@IP-miRNA NPs were successfully synthesized which have spherical shape, uniform size, good dispersion and positive potential. The encapsulation rate of IR780 was (82.58±3.92) %, the drug loading rate was (6.60±0.32) %, and the adsorption capacity of miRNA338-3p was 41.78 µg/mg. NPs have excellent tumor targeting ability, miRNA transfection ability, ROS production ability and multimodal imaging ability in vivo and in vitro. The antitumor effect of combined treatment group was the best, and the efficacy was better than that of single factor treatment group, and the difference was statistically significant. Conclusion: P@IP-miRNA NPs can realize multimodal imaging and sonodynamic-gene therapy, providing a new idea for accurate diagnosis and treatment of PTC.

Value of CEUS combined with feeding artery ablation in the microwave ablation of large solid benign thyroid nodules.

OBJECTIVES: To investigate the value of contrast-enhanced ultrasound (CEUS) combined with feeding artery ablation in the microwave ablation (MWA) of large solid benign thyroid nodules (LSBTNs) with a diameter ≥ 4 cm. METHODS: We retrospectively analyzed 122 patients with LSBTN ≥ 4 cm in diameter treated with MWA. During evaluations before and after MWA, 53 patients who underwent conventional ultrasound examination were classified as the routine group, and 69 patients who underwent CEUS combined with feeding artery ablation were classified as the union group. The differences in ablation energy required per milliliter (AERPM), complication rate, regrowth rate, and volume reduction rate (VRR) were compared between the two groups. RESULTS: The AERPM of the union group was significantly less than that of the routine group (956.3 ± 38.5 J/mL vs. 1025.9 ± 121.5 J/mL, p < 0.001). The complication rate of the routine group was significantly higher than that of the union group (13.2% vs. 2.9%, p = 0.031). The regrowth rate of the routine group (22.6%, 12/53) was significantly higher than that of the union group (7.2%, 5/69) (p = 0.015). At the 1st, 3rd, 6th, 12th, 18th, and 24th month after ablation, the mean VRRs of the routine group were significantly less than those of the union group, with p values of < 0.001, < 0.001, 0.002, 0.007, 0.013, and < 0.001, respectively. CONCLUSIONS: The application of CEUS combined with feeding artery ablation in the MWA of LSBTNs is helpful to reduce the regrowth rate, improve the ablation efficiency, and reduce bleeding. KEY POINTS: • CEUS combined with feeding artery ablation in MWA of LSBTNs is helpful to reduce regrowth rate. • CEUS combined with feeding artery ablation can help improve ablation efficiency than conventional ultrasound in LSBTNs. • CEUS combined with feeding artery ablation helps reduce the incidence of bleeding during MWA.

Effectiveness and Safety of Ultrasound-guided Percutaneous Microwave Ablation for a Single Uterine Fibroid Greater than 300 cm3.

STUDY OBJECTIVE: To evaluate the effectiveness and safety of ultrasound-guided percutaneous microwave ablation (MWA) for a single uterine fibroid greater than 300 cm3. DESIGN: Retrospective observational study. SETTING: China-Japan Union Hospital of Jilin University, China. PATIENTS: Thirty-seven patients each with a single fibroid greater than 300 cm3 diagnosed by ultrasound and core needle biopsy. INTERVENTIONS: Ultrasound-guided percutaneous MWA. MEASUREMENTS AND MAIN RESULTS: All patients were followed up for 12 months postoperatively to assess the postoperative lesion volume reduction rate, degree of symptomatic relief, improvements in quality of life, and occurrence of adverse events. All 37 patients met the criteria for complete ablation, and the lesion volume significantly decreased from 334.28 cm3 (95% confidence interval [CI] 326.75-366.73) preoperatively to 52.01 cm3 (95% CI, 46.95-74.69) at the 12-month follow-up (difference: 280.15 cm3; 95% CI, 267.92-294.65; p <.001). The lesion volume reduction rates at 1, 3, 6, and 12 months postoperatively were 27.30% (95% CI, 24.12-31.45), 52.90% (95% CI, 47.95-55.80), 67.90% (95% CI, 63.03-70.77), and 84.00% (95% CI, 80.22-85.94), respectively. The differences in the preoperative and postoperative Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire scores were significant (p <.01). The hemoglobin levels of the anemic patients were significantly elevated after the procedure (p <.001). Of the 37 patients in this study, 29 patients (78.38%) had a highly significant treatment effect, and 8 patients (21.62%) had a significant treatment effect. Seventeen patients (45.95%) had Society of Interventional Radiology grade A to B adverse effects that required no clinical intervention or only simple clinical intervention. CONCLUSION: Ultrasound-guided percutaneous MWA has good clinical efficacy and high safety in the treatment of a single uterine fibroid greater than 300 cm3.

Over than three-year follow-up results of thermal ablation for papillary thyroid carcinoma: A systematic review and meta-analysis.

Background: This study is a meta-analysis based on evidence-based medicine to explore the long-term (≥3 years) efficacy of thermal ablation in the treatment of papillary thyroid carcinoma (PTC). Methods: We searched the PubMed, Embase, and Cochrane Library databases for studies published during the time between the establishment of the databases through June 2022. We included 13 non-randomized-controlled trials (non-RCTs) that reported the application of ultrasound-guided thermal ablation in PTC. We excluded studies that were repeated publications, research without full text, contained incomplete information, lacked data extraction, involved animal experiments, reviews, and systematic reviews. STATA 15.1 software was used to analyze the data. Results: Tumor volume after thermal ablation at 3-year follow-up was significantly lower than pre-ablation (standardized mean difference [SMD] = -1.06, 95% CI: -1.32~-0.80). The pooled results indicated that the maximum diameter after thermal ablation at 3-year follow-up was significantly lower than pre-ablation (SMD = -1.93, 95% CI: -12.13~-1.73). The pooled results indicated that volume reduction rate (VRR) after thermal ablation at 3-year follow-up was 98.91% (95% CI: 97.98-99.83%), and complete disappearance rate (CDR) after thermal ablation at 3-year follow-up was 83% (95% CI: 67-94%). In addition, the incidence of newly discovered mPTC and lymph node metastases after thermal ablation was 0.3% (95% CI: 0.0-1.0%) and 0.0% (95% CI: 0.0-0.0%), respectively. Conclusion: Overall, the long-term (≥3 years) efficacy of ultrasound-guided thermal ablation in the treatment of PTC was significant, with favorable disease progression. Ultrasound-guided thermal ablation can be considered an alternative approach for patients with PTC who refuse surgery or are unable to undergo surgery.

Efficacy and safety of ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma: a systematic review and meta-analysis.

BACKGROUND: We comprehensively evaluate the efficacy and safety of US-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) via a systematic review and meta-analysis. METHODS: We searched the PubMed, Embase and Cochrane Library databases for studies published during the time between the establishment of the database through October 2021. We included a 10 non-randomized controlled trial (non-RCT) that reported the application of US-guided RFA in PTMC. The sample size of patients totaled 1279. We evaluated the ablation efficacy by analyzing the volume reduction rate (VRR), complete disappearance rate (CDR) and recurrence rate of PTMC treated by RFA. We analyzed all data using STATA version 15.1 (Stata Corporation, College Station, TX). RESULTS: Our pooled results proved RFA treatment significantly reduces the volume of tumors (Weighted Mean Difference [WMD] = -103.20, 95% CI: -111.93 - -94.48, p = 0.000). We also found the VRR at 12 months after RFA was 93.27% (95% CI: 84.68-101.86), and the CDR at 12 months after RFA was 64% (95% CI: 39-89%). Additionally, pooled results showed the incidence of mPTC residue in ablation area, newly discovered mPTC and lymph node metastases after RFA treatment were respectively 0.3% (95% CI: -0.1-0.7%), 2.5% (95% CI: 1.1-3.9%) and 1.0% (95% CI: 0.2-1.9%), and the incidence of complications after RFA treatment was 1.8% (95% CI: 0.7-3.2%). CONCLUSIONS: US-guided RFA is effective and safe for treating PTMC. It could be an excellent alternative to the existing treatment options.

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 Core Needle Biopsy Under the Assistance of Hydrodissection With Fine Needle Aspiration in the Diagnosis of High-Risk Cervical Lymph Nodes: A Randomized Controlled Trial.

A randomized comparison of ultrasound (US)-guided core needle biopsy (CNB) under the assistance of hydrodissection with fine needle aspiration (FNA) was performed to evaluate the feasibility, safety and effectiveness for the diagnosis of high-risk cervical lymph nodes. Patients from December 2018 to May 2020 were randomly assigned to the CNB group and the FNA group at a ratio of 1:1. This study protocol was approved by the Ethics Committee of our hospital and registered in the Chinese Clinical Trial Registry (ChiCTR1800019370). The feasibility of CNB for high-risk cervical lymph nodes was evaluated by observing and recording the separation success rate (SSR) and technical success rate (TSR) of the CNB group. Safety was evaluated by comparing the incidence of major complications in the two groups. The diagnostic efficacy was evaluated by comparing the diagnostic accuracy, sensitivity, and specificity of the two groups. A total of 84 patients (84 lymph nodes) were randomized into the CNB (n = 42) and FNA (n = 42) groups. All patients in the CNB group achieved successful hydrodissection and biopsy. The SSR and TSR were both 100% in the CNB group. There were no major complications during or after the process in the two groups. Compared with the FNA group, the CNB group was significantly superior in terms of diagnostic accuracy and sensitivity (100% vs. 81.0%, P = 0.009; 100% vs. 79.2%, P = 0.035, respectively). The specificity of the two groups was 100%, and there was no significant difference. Compared with FNA, CNB under the assistance of hydrodissection is a feasible and safe method but is more effective for the diagnosis of high-risk cervical lymph nodes. CLINICAL TRIAL REGISTRATION: http://www.medresman.org, ChiCTR1800019370.

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.

A photothermal-hypoxia sequentially activatable phase-change nanoagent for mitochondria-targeting tumor synergistic therapy.

To enhance the specificity and efficiency of anti-tumor therapies, we have designed a multifunctional nanoparticle platform for photochemotherapy using fluorescence (FL) and photoacoustic (PA) imaging guidance. Nanoparticles (NPs) composed of a eutectic mixture of natural fatty acids that undergo a solid-liquid phase transition at 39 °C were used to encapsulate materials for the rapid and uniform release of the hypoxia-activated prodrug tirapazamine (TPZ) and the photosensitizer IR780, which targets the mitochondria of tumor cells and can be used to induce hypoxic cell death via photodynamic therapy and photothermal therapy. In vitro, the NPs containing TPZ and IR7890 exhibited appreciable cell uptake and triggered drug release when irradiated with a NIR laser. In vivo, photochemotherapy of the NPs achieved the best anti-tumor efficacy under PA and FL imaging guidance and monitoring. By combining IR780 mitochondria-targeting phototherapy with TPZ, we observed improved anti-tumor effectiveness and this has the potential to reduce the side effects of traditional chemotherapy. Herein, we demonstrate a new intracellular photochemotherapy nanosystem that co-encapsulates photosensitizers and hypoxia-activated drugs to enhance the overall anti-tumor effect precisely and efficiently.

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.

Learnability and reproducibility of ACR Thyroid Imaging, Reporting and Data System (TI-RADS) in postgraduate freshmen.

PURPOSE: The Thyroid Imaging, Reporting and Data System (TI-RADS) from the American College of Radiology (ACR) has been used since 2017 for the evaluation of thyroid nodules. The purpose of this study is to assess the learnability and reproducibility of TI-RADS in postgraduate freshmen. METHODS: This was a retrospective study involving 400 nodules with a final diagnosis following ultrasound (US) examination. The nodules were randomized into eight groups (50/group). Three postgraduate freshmen and three experts evaluated the nodules according to ACR TI-RADS without knowledge of the final diagnosis. After evaluating each group, training was carried out based on the inconsistencies of the freshmen/experts. Training was stopped after 200 nodules because the κ value showed almost perfect concordance. Three months later, the 50 nodules of Group 4 (the last evaluated group) were re-evaluated to assess the reproducibility of ACR TI-RADS. RESULTS: The diagnostic accuracy of the three postgraduate freshmen increased from 60%, 48%, and 46% in Group 1 to 80%, 78%, and 72% in Group 4 (P= 0.029, 0.002, and 0.008), respectively. After training, the diagnostic accuracy of the postgraduate freshmen was close to that of the experts (84%). For the US features, the postgraduate freshmen were consistent with the experts (all κ > 0.6). When re-evaluating Group 4 three months later, the five features had substantial to almost perfect agreement for the same researcher (all κ > 0.7). CONCLUSION: Based on experts' consensus, ACR TI-RADS can be learned well, and its reproducibility is excellent.

Adeno-associated virus (AAV)-mediated neuroprotective effects on the degenerative retina: the therapeutic potential of erythropoietin.

Retinal degeneration (RD) results in photoreceptor loss and irreversible visual impairments. This study sought to alleviate the photoreceptor degeneration via the adeno-associated virus (AAV)-mediated erythropoietin (EPO) therapy. AAV-2/2-mCMV-EPO vectors were constructed and delivered into the subretinal space of a RD model. The retinal morphology, optokinetic behaviour and electrophysiological function of the treated animals were analysed. The subretinal delivery of AAV-2/2 vectors induced robust EPO gene expressions in the retinas. AAV2/2-mediated EPO therapy ameliorated the photoreceptor degeneration and visual impairments of the RD animal model. Furthermore, the multi-electrodes array (MEA) was used to detect the firing activities of retinal ganglion cells. MEA recording showed that the EPO therapy could restrain the spontaneous firing response, enhance the light-induced firing response and preserve the basic configurations of visual signal pathway in RD model. Our MEA assay provided an example to evaluate the potency of pharmacological compounds on retinal plasticity. In conclusion, AAV2/2-mediated EPO therapy can ameliorate the photoreceptor degeneration and rectify the abnormities in visual signal transmission. These beneficial results suggest the AAV vector is a viable therapeutic option for retinopathies with rapidly degenerating kinetics and lay the groundwork for future development of EPO gene therapy.

Clinical Application of Ultrasound Guidance for Parametrial Treatment of Advanced Cervical Cancer.

OBJECTIVES: To evaluate the accuracy of ultrasound (US) in determining the positions of parametrial implants by comparing US with magnetic resonance imaging (MRI) for advanced cervical cancer. METHODS: Patients undergoing brachytherapy with parametrial implantation for cervical cancer from February 2017 to February 2019 were involved in the study. The transverse section of the cervix (surface S1 ) and the transverse section 1 cm above the external cervix (surface S2 ) were selected from MRI and US images as the observation planes. In the MRI observation plane, the distances between the uterine titanium needles and the uterine tube/implanter were set as M1 to M4 ; in the US observation plane, the distances between the uterine titanium needles and the uterine tube/implanter were set as D1 to D4 . The differences and consistency in M and D of each group were then compared. RESULTS: There were no significant differences between M and D in each group (P = .058; P = .821; P = .870; and P = .936, respectively). The intraclass correlation coefficients of M and D in each group were 0.970, 0.968, 0.952, and 0.956. A regression analysis showed that the relationships between M and D in each group were as follows: M1 = 0.9449D1 + 0.1812; M2 = 0.9463D2 + 0.0965; M3 = 0.9176D3 + 0.1233; and M4 = 0.9253D4 + 0.1224. CONCLUSIONS: In parametrial brachytherapy for cervical cancer, US can accurately determine the positions of parametrial implantation needles, which is already applicable on MRI, and can provide assistance in parametrial brachytherapy for advanced cervical cancer.

A sequential targeting nanoplatform for anaplastic thyroid carcinoma theranostics.

Effective accumulation of nanoparticles (NPs) in tumor regions is one of the major motivations in nanotechnology research and that the establishment of an efficient targeting nanoplatform for the treatment of malignant tumors is urgently needed for theranostic applications. In this study, we engineered multifunctional sequential targeting NPs for achieving synergistic antiangiogenic photothermal therapy (PTT) and multimodal imaging-guided diagnosis for anaplastic thyroid carcinoma (ATC) theranostics. Antibody bevacizumab with an affinity towards vascular endothelial growth factor (VEGF) on the tumor cell surface was conjugated onto the surface of polymer NPs for VEGF targeting and antiangiogenic therapy. Encapsulated IR825 was employed as a photothermal agent (PTA) with a mitochondrial targeting capability, which further cascades NPs into mitochondria to enhance hyperthermic efficiency in the ablation of tumor cells. Importantly, the combination of bevacizumab and IR825 in a single nanosystem achieved desirable accumulations of NPs and that sequential targeted PTT combined with antiangiogenesis significantly promoted the therapeutic efficiency in eradicating tumors by near-infrared (NIR) laser irradiation. Furthermore, these NPs are extraordinary contrast agents for photoacoustic, ultrasound and fluorescence imaging applications, providing multimodal imaging capabilities for therapeutic monitoring and a precise diagnosis. Therefore, this multifunctional nanoplatform provides a promising theranostic strategy for extremely malignant ATC. STATEMENT OF SIGNIFICANCE: Anaplastic thyroid carcinoma (ATC), with extremely aggressive behavior, lacks a satisfactory therapeutic method and a comprehensive early diagnostic strategy. Herein, we successfully synthesized a sequential targeting nanoplatform (IR825@Bev-PLGA-PFP NPs) with theranostic function, which specifically binds to VEGF on the tumor cell surface and further cascades into mitochondria to achieve effective accumulation of NPs in the tumor regions. As a result, it solves the urgent demand for ATC detection and therapy. By breaking the limitation of traditional target, such as low efficacy and frequent recurrence as the results of low accumulation, sequential targeting combined with synergistic antiangiogenic PTT completely eradicates tumors without any residual tissue and side effect. Therefore, this strategy paves a solid way for further investigation in the theranostic progressing of ATC.