The purpose of this study was to evaluate the long-term efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) in a large population. From June 2014 to December 2017, 414 patients (323 females, 91 males, mean age 43.56 ± 9.79 years, range 18–73 years) with unifocal low-risk PTMC confirmed by core-needle biopsy (CNB) were treated by RFA. Patients were followed up at 1, 3, 6, and 12 months and every 6–12 months thereafter by ultrasound and contrast-enhanced ultrasound (CEUS). The volume and the volume reduction ratio (VRR) were calculated. Recurrence and lymph node or distant metastasis were evaluated. The mean initial volume was 92.74 ± 83.43 mm3 (range 4.19–490.07 mm3), which decreased significantly to 1.37 ± 7.94 mm3 (range 0–67.97 mm3) at a mean follow-up time of 42.15 ± 11.88 months (range 24–69 months) with a mean VRR of 98.81 ± 6.41% (range 50–100%). No life-threatening or delayed complications occurred. After RFA, 366 tumors (88.41%) completely disappeared. The overall incidence of local tumor progression rate was 3.62%. Among them, one patient (0.24%) was diagnosed to have residual cancer by CNB and underwent additional RFA. Four patients (0.97%) developed metastatic lymph node, and 10 patients (2.42%) had recurrent PTMC. A total of 13 patients underwent additional RFA, and 11 lesions completely disappeared during the follow-up. RFA is an effective and safety treatment for low-risk PTMC after a long-term follow-up period for a large cohort with careful patient enrollment evaluation. • Radiofrequency ablation is an effective and safe alternative for low-risk PTMC. • The overall incidence of local tumor progression rate was low. • No life-threatening or delayed complications occurred.

Long-term outcomes of radiofrequency ablation for unifocal low-risk papillary thyroid microcarcinoma: a large cohort study of 414 patients

To investigate the use of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in assessing local therapeutic response of percutaneous laser ablation (PLA) for papillary thyroid microcarcinoma (PTMC). Sixty-four patients with 64 PTMCs who were referred to our hospital from November 2013 to July 2016 were treated with PLA. The extent of ablation was assessed by CEUS at 10–20 min and 7 days after PLA. The size and volume of the ablation zone were evaluated on conventional ultrasound at 1 h, 1, 3, 6 and 12 months, and every half-year thereafter, and recurrences were also recorded. Ultrasound-guided fine needle aspiration biopsy (FNAB) of the ablated area was performed at 1, 6 and 12 months after PLA. Two incomplete ablations were detected by CEUS, and a second ablation was performed. The mean largest diameter and volume of the ablated area on CEUS at 10–20 min and 7 days after PLA were significantly larger than those of pre-treatment on conventional ultrasound (p < 0.05, for both). At the last follow-up, the mean largest diameter was reduced from 4.6 ± 1.5 to 0.6 ± 1.3 mm (p < 0.0.5), and the average volume was 41.0 ± 40.4 mm3, which decreased to 1.8 ± 6.7 mm3 (p < 0.0.5). A cervical metastatic lymph node was detected on ultrasound and confirmed by ultrasound-guided FNAB at 30 months after PLA. CEUS could play a crucial role in assessing the completeness of PLA for treating PTMC, and conventional ultrasound can not only guide the FNAB process but also is important in the follow-up of PTMC after PLA.

Percutaneous Laser Ablation of Unifocal Papillary Thyroid Microcarcinoma: Utility of Conventional Ultrasound and Contrast-Enhanced Ultrasound in Assessing Local Therapeutic Response.

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 progre...

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

Background: Thermal ablation (TA) has been applied in patients with low-risk papillary thyroid microcarcinoma (PTMC) who refuse surgery or active surveillance (AS). Recently, TA has been proposed a...

Ultrasound-Guided Radiofrequency Ablation Versus Thyroid Lobectomy for Low-Risk Papillary Thyroid Microcarcinoma: A Propensity-Matched Cohort Study of 884 Patients.

Purpose: Our study aims to compare ultrasound (US)-guided percutaneous microwave ablation (PMWA) and conventional thyroidectomy in benign thyroid nodules (BTN) treatment.Materials and methods: From December 2015 to December 2017, a total of 280 patients with at least one benign thyroid nodule were studied retrospectively, including 156 patients treated with US-guided PMWA and 124 patients treated with conventional thyroidectomy. Propensity score matching was performed to decrease the confounding bias due to retrospective assignment and to balance the pre-operation data of the two groups. A total of 106 pairs (1:1) was created. The operation time, intraoperative blood loss, postoperative hospitalization time, serum levels of interleukin (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) 12 h after operation and postoperative complications incidence rate were compared between the two groups. The volume reduction ratio was calculated in the US-guided PMWA group at 1, 3, 6 and 12 months...

A propensity score matching study between ultrasound-guided percutaneous microwave ablation and conventional thyroidectomy for benign thyroid nodules treatment

The prevalence of papillary thyroid microcarcinoma (PTMC) increases rapidly all around the world, but the management of PTMC hasn't reached a consensus. Recently, ultrasound-guided (US-guided) ablation therapy was introduced as a feasible treatment for low-risk PTMC. The clinical application of US-guided ablation therapy needs doctors' effort to investigate the efficacy and the safety of US-guided ablation in treating PTMC carefully. Although the present evidence showed some limitations, such as short-term study time spans and no randomized control design, in our perspective, US-guided thermal ablation therapy has good short-term efficacy and safety and is a promising PTMC's treatment in future clinical practice.

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The Efficacy and The Safety of Ultrasound-guided Ablation Therapy for Treating Papillary Thyroid Microcarcinoma

http://www.cell.com/article/S2589004222000037/pdf

Mechanosensitive channel Piezo1 induces cell apoptosis in pancreatic cancer by ultrasound with microbubbles

Sonodynamic therapy (SDT) induces immunogenic cell death (ICD) in tumors and promises to play an assistive role in immunotherapy in pancreatic cancer. However, the short half-life and limited diffusion distance of reactive oxygen species (ROS) impair ICD induction, especially in tumors with relatively poor blood perfusion and dense stroma.To address this problem, we fabricated cavitation-assisted endoplasmic reticulum (ER) targeted sonodynamic nanodroplets (PMPS NDs, 329 nm). The good sonodynamic effect and precise endoplasmic reticulum target effect was verified. After intravenous injection, the cRGD peptide modified nanodroplets initially aggregated around the tumor vascular endothelial cells. Stimulated by ultrasound, the liquid-to-gas bubbles began to oscillate and cavitate. This acoustic droplet evaporation strategy facilitated transport of the nanoparticle across the vessel, with deep penetration. This loosened the tumor stroma and facilitated accumulation and penetration of loaded sonosensitizer after 6 h. The modified sonosensitizer can selectively accumulate in the ER to generate a large amount of ROS in situ, inducing potent ER stress, amplified ICD and dendritic cell maturation in vitro and in vivo. Furthermore, the elevated antitumor effect of SDT plus anti-PD-L1 immunotherapy was verified using an orthotopic tumor model.This study reports a cavitation assisted ER targeted sonodynamic therapy that can enhance the effect of anti-PD-L1 immunotherapy effectively in orthotopic and distant pancreatic cancer. 

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Cavitation assisted endoplasmic reticulum targeted sonodynamic droplets to enhanced anti-PD-L1 immunotherapy in pancreatic cancer

Inefficient intracellular gene release and transfection limit nonviral gene delivery applications in cancer therapy. Reactive oxygen species (ROS) responsive nonviral gene delivery is the most widely explored strategy for such applications, yet the development of fast and safe ROS responsive nanocarriers proves to be a challenge because of the intracellular chemical equilibrium of high ROS and glutathione levels. Here, we report an ultrasound-enhanced ROS responsive charge-reversal polymeric nanocarrier (BTIL) for fast and efficient pancreatic cancer gene delivery. The BTIL is composed of B-PDEAEA/DNA polyplex-based cores and IR780-loaded liposome coatings. The IR780 is able to produce an excess of ROS under low intensity ultrasound irradiation, thus disequilibrating the chemical equilibrium of ROS and glutathione, and promoting the ROS-responsive positive-to-negative charge-reversal of the B-PDEAEA polymer. This charge conversion results in fast polyplex dissociation and intracellular gene release, inducing efficient gene transfection and cancer cell apoptosis. Moreover, following the intravenous administration, BTIL maintains a stable and long circulation in the bloodstream, achieves orthotopic pancreatic ductal adenocarcinoma distribution, and exhibits potent antitumor activity with negligible side effects. Our results reveal the proposed strategy to be both promising and universal for the development of fast and safe ROS responsive nonviral gene delivery in cancer therapy.

Ultrasound-Enhanced Reactive Oxygen Species Responsive Charge-Reversal Polymeric Nanocarriers for Efficient Pancreatic Cancer Gene Delivery.

Tumor drug resistance (TDR) invariably leads to the failure of chemotherapy. In addition, current treatment strategies for TDR are not satisfactory due to limitations in terms of safety and feasibility. The aim of the present study was to determine whether low-intensity low-frequency ultrasound (LILFU) could improve the effect of chemotherapy and reverse TDR in gemcitabine-resistant ASPC-1 (ASPC-1/GEM) cells. The investigation focused on the association between LILFU effectiveness and the adenosine triphosphate-binding cassette (ABC) transporters and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB signaling pathway. A Cell Counting Kit-8 assay was used to determine the appropriate acoustic intensity, half-maximal inhibitory concentration of gemcitabine (GEM) and the viability of ASPC-1/GEM cells. ASPC-1/GEM cells were divided into control, GEM, LILFU and GEM+LILFU groups. Cell proliferation was evaluated through colony formation assays, whereas cell apoptosis was detected using flow cytometry. Western blotting was used to explore the expression levels of ABC transporters and PI3K/AKT/NF-κB signaling pathway-associated proteins. Xenograft models in mice were established to identify the enhancing effect of GEM+LILFU in vivo. Immunohistochemistry was used to detect the expression levels of Ki-67 in tumor tissues. The acoustic parameter of 0.2 W/cm2 and a GEM concentration of 6.63 mg/ml were used in subsequent experiments. Following treatment with GEM+LILFU, the cell viability and proliferation ability were decreased, whereas the apoptotic rate was increased compared with the GEM group. The expression levels of ABC transporters, PI3K-P110α and NF-κB were decreased in the GEM+LILFU group. Notably, LILFU increased the effectiveness of GEM in inhibiting tumor growth, and reduced the expression levels of Ki-67 in the xenograft mouse model. LILFU improved the chemosensitivity of ASPC-1/GEM cells via inhibition of cell viability and proliferation, and promoted cell apoptosis in the GEM+LILFU group. In conclusion, LILFU may downregulate the expression levels of ABC transporters by inhibiting the PI3K-p110α/AKT/NF-κB signaling pathway, thereby reversing resistance in pancreatic cancer.

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Low‑intensity low‑frequency ultrasound enhances the chemosensitivity of gemcitabine‑resistant ASPC‑1 cells via PI3K/AKT/NF‑κB pathway‑mediated ABC transporters

Jifan Chen

Papers

The Efficacy and The Safety of Ultrasound-guided Ablation Therapy for Treating Papillary Thyroid Microcarcinoma

Mechanosensitive channel Piezo1 induces cell apoptosis in pancreatic cancer by ultrasound with microbubbles

Cavitation assisted endoplasmic reticulum targeted sonodynamic droplets to enhanced anti-PD-L1 immunotherapy in pancreatic cancer

Ultrasound-Enhanced Reactive Oxygen Species Responsive Charge-Reversal Polymeric Nanocarriers for Efficient Pancreatic Cancer Gene Delivery.

Low‑intensity low‑frequency ultrasound enhances the chemosensitivity of gemcitabine‑resistant ASPC‑1 cells via PI3K/AKT/NF‑κB pathway‑mediated ABC transporters