Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Efficacy and safety of microwave ablation for the treatment of multifocal versus unifocal T1N0M0 papillary thyroid carcinoma: a propensity-matched multicentre retrospective study.

OBJECTIVES: Microwave ablation (MWA) has been widely used for unifocal papillary thyroid carcinoma (U-PTC) and has recently been preliminarily used in multifocal papillary thyroid carcinoma (M-PTC). However, the efficacy and safety of MWA for M-PTC have not been investigated in large samples. The aim of the present study was to evaluate the efficacy and safety of MWA for M-PTC and compare them with MWA for U-PTC. MATERIALS AND METHODS: This retrospective multicentre study enrolled 504 patients (376 females) who underwent MWA for U-PTC (340 cases) or M-PTC (164 cases) from Jan 2015 to Dec 2020. The median age of the patients was 43 years (age range, 20-80 years). Propensity score matching (PSM) was used to balance the baseline characteristics between M-PTC group and U-PTC group. The tumour progression, tumour disappearance, and complication rates were compared between the two groups. RESULTS: The complete ablation was achieved in all enrolled cases in one session. According to the statistical results, no significant differences were shown in tumour progression-free survival (p  = 0.29) or cumulative tumour progression rate (6.7% vs. 4.3%, p  = 0.33) between the M-PTC and U-PTC groups during the follow-up time. However, the tumour disappearance rate in the M-PTC group was lower in the U-PTC group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the M-PTC group (p < 0.001). The complication rate showed no significant difference (3.0% vs. 4.9%, p  = 0.571). CONCLUSIONS: MWA is an effective and safe treatment for selected patients with M-PTC, and the prognosis is similar to that of U-PTC. CLINICAL RELEVANCE STATEMENT: The present study provided evidence that compared with unifocal papillary thyroid cancer, microwave ablation could also treat multifocal T1N0M0 papillary thyroid cancer safely with similar clinical outcome, which could promote the application of minimally invasive treatment for papillary thyroid cancer. KEY RESULTS: • Microwave ablation for multifocal and unifocal T1N0M0 papillary thyroid carcinoma had similar tumour progression rates after propensity score matching (6.7% vs. 4.3%, p = 0.33). • The tumour disappearance rate in the multifocal group was lower than that in the unifocal group (40.9% vs. 62.8%, p < 0.001), and tumour disappearance was slower in the multifocal group (p < 0.001). • Tumour size, number, and location were not risk factors for tumour progression in the multifocal papillary thyroid cancer group.

Stereochemistry of Chiral 2-Substituted Chromanes: Twist of the Dihydropyran Ring and Specific Optical Rotation.

Chiral 2-substituted chromanes are important substructures in organic synthesis and appear in numerous natural products. Herein, the correlation between specific optical rotations (SORs) and the stereochemistry at C2 of chiral 2-substituted chromanes was investigated through data mining, quantum-chemical calculations using density functional theory (DFT), and mechanistic analyses. For 2-aliphatic (including acyloxy and alkenyl) chromanes, the P-helicity of the dihydropyran ring usually corresponds to a positive SOR; however, 2-aryl chromanes with P-helicity tend to exhibit negative SORs. 2-Carboxyl (including alkoxycarbonyl and carbonyl) chromanes often display small experimental SORs, and theoretical calculations for them are prone to error because of the fluctuating conformational distribution with computational parameters. Several typical compounds were discussed, including detailed descriptions of the asymmetric synthesis, absolute configuration (AC) assignment methods, and systematic conformational analysis. We hope this work will enrich the knowledge of the stereochemistry of chiral 2-substituted chromanes.

Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity.

Polycyclic aromatic systems have been considered good biological probes, but some may also be good scaffolds for drug development. In this study, a series of benzobis(imidazole) derivatives were identified as STAT3 signal inhibitors, among which compound 24 showed significant inhibition of IL-6 induced JAK/STAT3 signalling pathway activation. Moreover, 24 inhibited cancer cell growth and migration, and induced cell apoptosis as well as cycle arrest in human hepatocellular carcinoma cells (HepG2) and oesophageal carcinoma cells (EC109). Compound 24 also displayed obvious antitumor activity in a mouse HepG2 cell xenograft tumor model without affecting the body weight. These results confirmed that 24 was a potential STAT3 signal inhibitor with certain antitumor activity.

Factors related to the absorption rate of benign thyroid nodules after image-guided microwave ablation: a 3-year follow-up.

PURPOSE: To assess the absorption rate and factors related to the development of benign thyroid nodules (BTNs) following image-guided microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study reviewed nodule efficacy in patients who underwent MWA of BTNs between January 2016 and January 2018. The endpoint was a third-year follow-up. Nodules were categorized into those showing complete absorption (volumes with less than 100% volume reduction ratio (VRR) and those showing partial absorption (100% VRR)). Univariable and multivariable regression analyses were carried out to identify variables that were associated with nodule absorption rates. RESULTS: A total of 173 BTNs (median volume= 4.23 ml; 25-75 percentiles= 2.27-9.00 ml) from 173 patients were evaluated. 49.7% (86/173) of patients had nodules that became completely absorbed. The mean VRRs of all BTNs were 18.0%, 78.7%, 89.0%, 94.5%, and 97.1% at the 1-, 6-,12-, 24- and 36- month follow-ups. At the 3-year follow-up time point, nodule characteristics related to nodule VRR included nodule volume (adjusted odds ratio [AOR], 1.1 [95% CI: 1.0, 1.2]; p = 0.03) and nodule margin (AOR, 5.3 [95% CI: 1.8, 16.0]; p < 0.01). Treatment-related characteristics included energy per ml in nodular volume (AOR, 1.0 [95% CI: 1.0, 1.0]; p < 0.01) and blockage of peripheral flow (AOR, 3.3 [95% CI: 1.3 8.3]; p = 0.01). CONCLUSIONS: US-guided image-guided MWA results in satisfactory long-term outcomes for the patients with BTNs. Factors related to nodule absorption rate were the volume and margin of the nodule, energy per ml in nodular volume and blockage of peripheral flow.

A nonneglectable stereochemical factor in drug development: Atropisomerism.

Chirality is one of the key factors affecting the medicinal efficacy of compounds. In addition to central chirality, sterically hindered chiral axes commonly appear in drugs and the resulting chirality is known as atropisomerism. With developments in medicinal chemistry, atropisomerism has attracted increasing attention. This review discusses the classification, biological activity, pharmacokinetics, toxicity and side effects of atropisomers, and can serve as a reference in the research and development of potential chiral drugs.

Novel predictive tools and therapeutic strategies for patients with initially diagnosed glottic cancer in the United States.

OBJECTIVE: The objective of this study is to identify valuable prognostic factors, build clinical prediction nomograms, and recommend the optimal therapeutic strategy for patients with initially diagnosed glottic cancer. METHODS: Patients were extracted from the SEER database. Cox regression analyses, survival analyses, an internal validation, the propensity score analysis, and the competing risk analysis were performed. RESULTS: Nine overlapped factors were considered as valuable prognostic factors. Furthermore, nomograms were established for clinical prediction models to assess the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS). C-indexes, receiver operating characteristic curves, calibration curves, and decision curve analyses proved that nomograms showed better predictive accuracy, ability, and prognostic value compared to the American Joint Committee on Cancer stage. For patients in stage I, primary site surgery alone would acquire best OS and CSS. For patients in stage II, primary site surgery and/or radiation would gain better OS and CSS. For patients in stage III, radiation plus chemotherapy or primary site surgery (alone or plus radiation) would acquire better OS and CSS. Moreover, for patients in stage IV, primary site surgery plus radiation would gain better OS and CSS. CONCLUSIONS: Nomograms could be useful for patients' counseling and guide therapeutic decision-making. Primary site surgery alone may likely be the optimal therapy for stage I glottic cancer, and primary site surgery and/or radiation may be the recommended therapy for stage II glottic cancer. The combination treatment would be the preferred choice for advanced-stage (stage III & IV) glottic cancer, and the role of chemotherapy needs to be further explored.

Correlations between the ECD spectra and absolute configuration of bridged-ring lactones: revisiting Beecham's rule.

Bridged lactones frequently appear as structural fragments in natural products. To elucidate their stereochemistry using electronic circular dichroism (ECD) spectra, Beecham correlated the sign of the Cotton effect (CE) from the n → π* transition of lactones at approximately 220 nm with the skeleton of bridged lactones. By combining experimental and theoretical ECD analyses of various bridged lactones using time-dependent density functional theory calculations and a methodology for extracting core structures, Beecham's rule was revisited and revised to define the scope of application. Both the position of the ß-C atom in the larger lactone system and the additive contribution of groups at ß-C exerted effects on the sign of the CE. The revised rule provides an alternative way to interpret experimental ECD data in addition to quantum-chemical calculation for various bridged lactones.

Identification of core miRNA prognostic markers in patients with laryngeal cancer using bioinformatics analysis.

PURPOSE: Lots of studies indicated that many microRNAs (miRNAs) are associated with the prognosis of patients with laryngeal cancer (LC). The objective of our study is to identify potential core miRNAs associated with the pathogenesis and prognosis of LC. METHODS: Using the Cancer Genome Atlast database, we identified 70 differentially expressed miRNAs between LC tumor specimens and non-tumor specimens. Then Cox regression analyses and the least absolute shrinkage and selection operator regression signature were performed to detect miRNA prognostic markers. A nomogram integrating miRNA prognostic markers was constructed to predict overall survival (OS) for LC patients. The potential target genes of the key miRNA were predicted by miRTarBase and miRDB databases. Subsequently, their potential functions were revealed by gene ontology annotation and kyoto encyclopedia of genes and genomes pathway enrichment analysis. Related biological pathways of the key target gene involved in LC were detected through gene set enrichment analysis (GSEA). RESULTS: A prognostic miRNA signature was constructed. The up-regulated miR-105-1 was related to a worse OS (p = 0.043), which suggested that miR-105-1 may likely be the key miRNA prognostic marker. Survival analyses and paired expression analyses of target genes indicated that ENDOU may be the key target gene. Finally, we conducted GSEA to elucidate the pathways enriched between low- and high-ENDOU expression datasets. CONCLUSION: Our findings might bring some new light on the pathogenesis of LC. Then, it might facilitate doctors to predict the prognosis and improve treatment outcomes for LC patients. However, the behaviors of LC are relatively heterogeneous, and the TCGA database cannot provide detailed information about the subsites and treatment modalities of LC. Further molecular biological experiments and clinical investigations would be required to confirm this conclusion.

Prognostic risk factors for initially diagnosed T2N0M0 glottic cancer: competing risk analysis and propensity-score matched cohort analysis.

BACKGROUND: Prognostic risk factors of patients with initially diagnosed T2N0M0 glottic cancer remain unclear. This study was aimed to conduct a comprehensive analysis to identify valuable prognostic risk factors for initially diagnosed T2N0M0 glottic cancer. METHODS: Data of patients with initially diagnosed T2N0M0 glottic cancer were extracted from the Surveillance, Epidemiology, and End Results database. Survival analyses and Cox regression analyses were conducted to evaluate overall survival (OS) and cancer-specific survival (CSS). In consideration of competing events, the competing risk (CR) analysis was applied. Furthermore, propensity-score matching (PSM) was applied to mimic randomized-controlled trials and reduce selection bias. RESULTS: A total of 923 eligible patients met the inclusion criteria. Survival analyses showed that age, marital status, primary site surgery, and radiation were independent predictors of OS. Besides, age, marital status, primary site surgery, radiation, and chemotherapy were independent predictors of CSS. Cox regression analyses and the CR analysis were basically consistent with this result. In addition, an internal validation and PSM were performed to explore the role of chemotherapy. CONCLUSION: We conducted a comprehensive analysis to prove that age, marital status, primary site surgery, radiation, and chemotherapy may be valuable prognostic risk factors for initially diagnosed T2N0M0 glottic cancer. Primary site surgery and radiation should be recommended, whereas chemotherapy was likely not suitable so far. Furthermore, we constructed a CR nomogram to predict survival rates.

FeNi Alloy Nanoparticles Encapsulated in Carbon Shells Supported on N-Doped Graphene-Like Carbon as Efficient and Stable Bifunctional Oxygen Electrocatalysts.

The development of cost-effective and durable oxygen electrocatalysts remains highly critical but challenging for energy conversion and storage devices. Herein, a novel FeNi alloy nanoparticle core encapsulated in carbon shells supported on a N-enriched graphene-like carbon matrix (denoted as FeNi@C/NG) was constructed by facile pyrolyzing the mixture of metal salts, glucose, and dicyandiamide. The in situ pyrolysis of dicyandiamide in the presence of glucose plays a significant effect on the fabrication of the porous FeNi@C/NG with a high content of doped N and large specific surface area. The optimized FeNi@C/NG catalyst displays not only a superior catalytic performance for the oxygen reduction reaction (ORR, with an onset potential of 1.0 V and half-wave potential of 0.84 V) and oxygen evolution reaction (OER, the potential at 10 mA cm-2 is 1.66 V) simultaneously in alkaline, but also outstanding long-term cycling durability. The excellent bifunctional ORR/OER electrocatalytic performance is ascribed to the synergism of the carbon shell and FeNi alloy core together with the high-content of nitrogen doped on the large specific surface area graphene-like carbon.

Selenium (Se) Does Not Reduce Cadmium (Cd) Uptake and Translocation in Rice (Oryza sativa L.) in Naturally Occurred Se-Rich Paddy Fields with a High Geological Background of Cd.

This study examined the selenium (Se) and cadmium (Cd) uptake by rice from soil and analyzed the relationship between Se and Cd in naturally occurred Se-rich paddy fields with a high geological background of Cd. Significant correlations were observed between soil Se and plant biomass Se, but not between soil Cd and plant biomass Cd. High concentrations of Cd were detected in rice plants and particularly in rice grains, suggesting potential health risks to human. Contrary to results from other previous studies, our results showed that high soil Se did not reduce Cd uptake by rice, although it decreased the availability of Cd in soil. Rather, soil Se and internal Se pool in rice were positively correlated to the transfer of Cd from root to straw. The effect of Se on the uptake and translocation of Cd in rice in field is therefore different from those in pot experiments.

Enantioseparation, Stereochemical Assignment and Chiral Recognition Mechanism of Sulfoxide-Containing Drugs.

The distinct pharmacodynamic and pharmacokinetic properties of enantiopure sulfoxide drugs have stimulated us to systematically investigate their chiral separation, stereochemical assignment, and chiral recognition mechanism. Herein, four clinically widely-used sulfoxide drugs were chosen and optically resolved on various chiral stationary phases (CSPs). Theoretical simulations including electronic circular dichroism (ECD) calculation and molecular docking were adopted to assign the stereochemistry and reveal the underlying chiral recognition mechanism. Our results showed that the sequence of calculated mean binding energies between each pair of enantiomers and CSP matched exactly with experimentally observed enantiomeric elution order (EEO). It was also found that the length of hydrogen bond might contribute dominantly the interaction between two enantiomers and CSP. We hope our study could provide a fresh perspective to explore the stereochemistry and chiral recognition mechanism of chiral drugs.

Multi-omics pan-cancer analysis reveals the prognostic values and immunological functions of PPA2, with a spotlight on breast cancer.

Background: Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer. Methods: A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity. Results: PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed. Conclusion: In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors.

A Large Vestibular Aqueduct With Conductive Hearing Loss as the Only Manifestation.

Conductive hearing loss is a common clinical condition caused by disorders of the middle and external ear. Here, we report a case of conductive hearing loss with complete tympanic membranes. Clinical examinations revealed no external and middle ear lesions, but high-resolution temporal bone computed tomography revealed enlarged vestibular aqueducts. Detailed audiological tests and follow-up results indicate that the exclusive air-bone gap is the outcome of inner ear malformation but not middle ear lesions, preventing the need for tympanic assessment.

A Large Intratemporal Facial Nerve Schwannoma Presenting as an Occluding External Auditory Canal Mass.

Facial nerve schwannomas are rare, benign, slow-growing tumors that can occur in any segment of the facial nerve, although 71% of cases are intratemporal. Surgical resection can lead to facial nerve injury. Facial function recovery after reanimation is usually not better than House-Brackmann (HB) grade III. Thus, for cases of intratemporal facial nerve schwannomas (IFNSs) with favorable facial function (HB grade I or II), observation by periodic magnetic resonance imaging is the mainstay of management. Here, we present a case of a large IFNS with normal facial function in which the mass fully occluded the external auditory canal. The occlusion caused squamous debris to accumulate, potentially leading to cholesteatoma. Faced with this therapeutic dilemma, we chose surgical resection with the patient's informed consent. Stripping surgery was achieved with normal postoperative facial function. There was no postoperative facial paralysis or recurrence at 2-year follow-up. We describe the experience of diagnosis and treatment process for this case, and discuss the possibility of total resection of the tumor with preserving the integrity of facial nerve.

Discovery, Optimization, and Evaluation of Novel N-(Benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine Analogues as Potent STAT3 Inhibitors for Cancer Treatment.

Signal transducer and activator of transcription 3 (STAT3) is an attractive target for cancer therapy. However, identifying potent and selective STAT3 small-molecule inhibitors with drug-like properties remains challenging. Based on a scaffold combination strategy, compounds with a novel N-(benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine scaffold were designed and their inhibition of the interleukin-6 (IL-6)/JAK/STAT3 pathway was tested in HEK-Blue IL-6 reporter cells. After optimization of lead compound 12, compound 40 was identified as a selective STAT3 inhibitor that directly binds the SH2 domain to inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. Compound 40 exhibited antiproliferative activities against STAT3-overactivated DU145 (IC50 value = 2.97 µM) and MDA-MB-231 (IC50 value = 3.26 µM) cancer cells and induced cell cycle arrest and apoptosis. In the DU145 xenograft model, compound 40 showed in vivo antitumor efficacy following intraperitoneal administration, with a tumor growth inhibition rate of 65.3% at 50 mg/kg, indicating promise for further development.

Specific chiroptical sensing of cysteine via ultrasound-assisted formation of disulfide bonds in aqueous solution.

Cysteine (Cys) can serve as a biomarker to indicate diseases or disorders, and its chiral sensing has attracted increasing attention. Herein, we established an ultrasound-facilitated chiral sensing method for Cys using 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) and electronic circular dichroism (ECD) spectroscopy. The formation of chiral disulfide bonds induced degenerate exciton coupling between two NBD chromophores, resulting in intense Cotton effects (CEs) of the sensing product. The anisotropy factor (g) was linearly correlated with the enantiomeric excess of Cys across the visible region (400-500 nm), and other natural amino acids or biothiols did not interfere with the detection. This ultrasound-promoted efficient and specific chiral sensing method of Cys has potential for application in the diagnosis of related diseases.

Internal Jugular Vein Thrombosis After Microwave Ablation of Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Case Report.

In this study, two patients with papillary thyroid carcinoma and lymph node metastasis were treated by Dr. Shurong Wang's team and are reported. The two patients refused surgery and underwent microwave ablation (MWA) of the thyroid and lymph node lesions. Ultrasound review 2 days after MWA revealed internal jugular vein thrombosis. Patient #1 received low molecular weight heparin calcium injection, Xueshuantong injection, Xiangdan injection, and rivaroxaban. Patient #2 was treated with enoxaparin sodium injection, Xueshuantong injection, urokinase, and warfarin sodium tablet. The thrombus was successfully managed in each patient using anticoagulant treatment. Such complication of MWA has not been reported in many cases before. According to the relevant literature, thrombosis after thyroid cancer ablation might be related to subclinical hypothyroidism, increased heme oxidase 1 (HO-1) levels in the blood of patients with papillary thyroid cancer, and increased platelet content and mean platelet volume in patients with thyroid cancer. No specific cause of thrombosis was identified in the two cases reported here. No recurrence was observed after 1 (patient #1) and 4 (#2) years of follow-up. In conclusion, patients with papillary thyroid carcinoma and lymph node metastasis should undergo color Doppler ultrasound of the neck after MWA of thyroid lesions and neck metastasis.