Radiofrequency ablation for capsular-located versus noncapsular-located papillary thyroid microcarcinoma: a propensity score matching study of 1095 patients.

OBJECTIVES: To assess the safety and efficacy of radiofrequency ablation (RFA) for capsular-located papillary thyroid microcarcinoma (PTMC) in a large cohort and to compare its outcomes with those of noncapsular-located PTMC. METHODS: We retrospectively reviewed patients who underwent RFA for solitary capsular-located and noncapsular-located low-risk PTMC (n = 1095) from June 2014 to October 2020. To balance confounding variables between capsular and noncapsular groups, we employed the 1:1 propensity score matching approach. We evaluated and compared tumor changes, disease progression, and complications in both groups. Furthermore, we analyzed the association between capsular location and disease progression using multivariable Cox regression. RESULTS: During a mean follow-up time of 29.86 ± 16.14 months and 29.73 ± 15.69 months, no substantial difference was observed between capsular and noncapsular groups in the latest volume (0.83 ± 3.66 mm3 vs. 0.85 ± 3.67 mm3, p = 0.44) and volume reduction ratio (99.29 ± 4.04% vs. 99.43 ± 3.03%, p = 0.43), and cumulative disappearance rate (87.87% vs. 86.07%, p = 0.31). In addition, no significant differences were observed in complication incidence (1.35% vs. 1.12%, p = 0.76) and progression-free survival (p = 0.53). Based on adjusted multivariate Cox proportional hazard analysis, the association between capsular location and disease progression was nonsignificant (all p > 0.05). CONCLUSION: This study demonstrates that the short-term outcomes of RFA for capsular-located PTMCs are comparable to those of noncapsular-located PTMCs. These findings indicate that RFA may be a viable and effective alternative for eligible patients with solitary capsular-located PTMC. CLINICAL RELEVANCE STATEMENT: Radiofrequency ablation may serve as a safe and effective alternative treatment method for eligible patients with capsular-located and noncapsular-located papillary thyroid microcarcinoma. KEY POINTS: • The safety and efficacy of radiofrequency ablation for capsular-located and noncapsular-located papillary thyroid microcarcinomas were comparable. • Disease progression did not differ significantly between capsular-located and noncapsular-located papillary thyroid microcarcinomas. • The incidence of complications for capsular-located papillary thyroid microcarcinoma was low.

Radiofrequency ablation for papillary thyroid microcarcinoma with a trachea-adjacent versus trachea-distant location.

OBJECTIVE: To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea. METHODS: Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated. RESULTS: A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73). CONCLUSION: For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

Sonographic Evolution and Pathologic Findings of Papillary Thyroid Cancer After Radiofrequency Ablation: A Five-Year Retrospective Cohort Study.

Background: The criteria for determining technical efficacy of thermal ablation for papillary thyroid carcinoma (PTC) are not clearly defined. We analyzed the involution process of the ablation zone with clear pathologic results on core-needle biopsy (CNB) to clarify the relationship between sonographic changes and pathologic findings. Methods: This retrospective cohort study included 382 patients with unifocal T1N0M0 PTC who underwent radiofrequency ablation (RFA) between May 2014 and August 2021. Patients with a single ablation zone biopsy (recommended at 3 or 6 months for T1a and 6 or 12 months for T1b) and regular neck ultrasound (US)/contrast-enhanced ultrasound imaging follow-up at 1, 3, 6, and 12 months and every 6-12 months thereafter after RFA were included. Patients also underwent yearly chest computed tomography. CNB was performed in the target lesion ablation zone's central, peripheral, and surrounding thyroid parenchyma to detect the presence of tumor cells. If the thyrotropin (TSH) was >2 mU/L, levothyroxine was prescribed with the intention of keeping the TSH 0.5-2 mU/L. Technical efficacy was defined as tumor disappearance by imaging follow-up together with the pathologically confirmed absence of tumor cells in the ablation zone. Results: During the mean follow-up period of 67.8 ± 18.2 months (22-110 months), the overall incidence of persistent disease and the technical efficacy rate were 3.9% (15/382; 2.9% of T1a, and 12.2% of T1b) and 96.1%, respectively. Tumor size (p = 0.03) and subcapsular location (p = 0.04) were risk factors associated with persistent disease. The technical success rate was 100%. Of the 367 ablation zones with benign CNB results, 336 (91.6%) showed tumor disappearance on US and no re-emergence of imaging-visible tumors during follow-up. Male sex (p = 0.006), age <40 years (p = 0.003), T1a tumor (p < 0.01), and energy per milliliter (p < 0.03) were significantly associated with tumor disappearance. Conclusions: US-guided RFA is an effective treatment for small low-risk PTC. Tumor disappearance on US after RFA may suggest an excellent prognosis and confirm complete ablation of the macroscopic tumor, but this sonographic finding is generally late and requires histological confirmation.

Prospective comparison of an 18-gauge versus 16-gauge needle for percutaneous liver core-needle biopsy in children.

PURPOSE: The objective of this study was to analyzed the impact of needle gauge (G) on the adequacy of specimens and hemorrhagic complications in pediatric patients undergoing ultrasound (US)-guided transplanted liver biopsies. METHODS: The study included 300 consecutive biopsies performed in 282 pediatric patients (mean age 6.75 ± 3.82 years, range 0.84-17.90) between December 2020 and April 2022. All pediatric patients that referred to our institution for US-guided core-needle liver biopsy (CNLB) were randomized to undergo 16-G or 18-G CNLB. Hemorrhagic complications were qualitatively evaluated. The number of complete portal tracts (CPTs) per specimen was counted and specimen adequacy was assessed based on the American Association for the Study of Liver Diseases guidelines. RESULTS: The incidence of bleeding was 7.00% (n = 21) and adequate specimens for accurate pathological diagnosis were obtained from 98.33% (n = 295) of patients. There was no significant difference in the incidence or amount of bleeding between the 16-G and 18-G groups (11 vs 10, p = 0.821; 35.0 mL vs 31.3 mL, p = 0.705). Although biopsies obtained using a 16-G needle contained more complete portal tracts than those obtained using an 18-G needle (20.0 vs 18.0, p = 0.029), there was no significant difference in specimen inadequacy according to needle gauge (2 vs 3, p = 1.000). CONCLUSIONS: Biopsy with a 16-G needle was associated with a greater number of CPTs but did not increase the adequate specimen rate. There was no significant difference in the complication rate between 16-G biopsy and 18-G biopsy.

Five-year Outcome Between Radiofrequency Ablation vs Surgery for Unilateral Multifocal Papillary Thyroid Microcarcinoma.

CONTEXT: Ultrasound (US)-guided radiofrequency ablation (RFA) has been considered as an alternative to surgery or active surveillance for papillary thyroid microcarcinoma (PTMC). However, little is known about the long-term outcomes of RFA in comparison with surgery for unilateral multifocal PTMC. OBJECTIVE: This work aims to report the comparison between RFA vs surgery for unilateral multifocal PTMC over a more than 5-year follow-up period. METHODS: This was a retrospective study at a primary care center with a median follow-up period of 72.9 months. A total of 97 patients with unilateral multifocal PTMC were treated with RFA (RFA group, n = 44) or surgery (surgery group, n = 53). In the RFA group, patients were treated by a bipolar RFA generator and an 18-gauge bipolar RF electrode with a 0.9-cm active tip. In the surgery group, patients underwent thyroid lobectomy with prophylactic central neck dissection. RESULTS: During the follow-up, no statistically significant differences were found in disease progression (4.5% vs 3.8%; P = ≥.999), lymph node metastasis (2.3% vs 3.8%; P = ≥.999), persistent lesion (2.3% vs 0%; P = .272), and RFS rates (97.7% vs 96.2%; P = .673) in the RFA and surgery groups. Patients undergoing RFA had a shorter hospitalization (0 vs 8.0 [3.0] d; P < .001), shorter procedure time (3.5 [2.4] vs 80.0 [35.0] min; P < .001), lower estimated blood loss (0 vs 20.0 [15.0] mL; P < .001), and lower costs ($1768.3 [0.1] vs $2084.4 [1173.8]; P = .001) than those in the surgery group. The complication rate in the surgery group was 7.5%, whereas none of the RFA-treated patients experienced any complications (P = .111). CONCLUSION: This study revealed 6-year comparable outcomes between RFA and surgery for unilateral multifocal PTMC. RFA may be a safe and effective alternative to surgery in selected patients with unilateral multifocal PTMC.

Investigation of a bacteriochlorin-containing pentad array for panchromatic light-harvesting and charge separation.

A new pentad array designed to exhibit panchromatic absorption and charge separation has been synthesized and characterized. The array is composed of a triad panchromatic absorber (a bis(perylene-monoimide)-porphyrin) to which are appended an electron acceptor (perylene-diimide) and an electron donor/hole acceptor (bacteriochlorin) in a crossbar arrangement. The motivation for incorporation of the bacteriochlorin versus a free-base or zinc chlorin utilized in prior constructs was to facilitate hole transfer to this terminal unit and thereby achieve a higher yield of charge separation across the array. The intense S0 → S1 (Qy) band of the bacteriochlorin also enhances absorption in the near-infrared spectral region. Due to synthetic constraints, a phenylethyne linker was used to join the bacteriochlorin to the core porphyrin of the panchromatic triad rather than the diphenylethyne linker employed for the prior chlorin-containing pentads. Static and time-resolved photophysical studies reveal enhanced excited-state quenching for the pentad in benzonitrile and dimethyl sulfoxide compared to the prior chlorin-containing analogues. Success was only partial, however, as a long-lived charge separated state was not observed despite the improved energetics for the final ground-state hole/electron-shift reaction. The apparent reason is more facile competing charge-recombination due to the shorter bacteriochlorin - porphyrin linker that increases electronic coupling for this process. The studies highlight design criteria for balancing panchromatic absorption and long-lived charge separation in molecular architectures for solar-energy conversion.

Dyads with tunable near-infrared donor-acceptor excited-state energy gaps: molecular design and Förster analysis for ultrafast energy transfer.

Bacteriochlorophylls, nature's near-infrared absorbers, play an essential role in energy transfer in photosynthetic antennas and reaction centers. To probe energy-transfer processes akin to those in photosynthetic systems, nine synthetic bacteriochlorin-bacteriochlorin dyads have been prepared wherein the constituent pigments are joined at the meso-positions by a phenylethyne linker. The phenylethyne linker is an unsymmetric auxochrome, which differentially shifts the excited-state energies of the phenyl- or ethynyl-attached bacteriochlorin constituents in the dyad. Molecular designs utilized known effects of macrocycle substituents to engineer bacteriochlorins with S0 → S1 (Qy) transitions spanning 725-788 nm. The design-predicted donor-acceptor excited-state energy gaps in the dyads agree well with those obtained from time dependent density functional theory calculations and with the measured range of 197-1089 cm-1. Similar trends with donor-acceptor excited-state energy gaps are found for (1) the measured ultrafast energy-transfer rates of (0.3-1.7 ps)-1, (2) the spectral overlap integral (J) in Förster energy-transfer theory, and (3) donor-acceptor electronic mixing manifested in the natural transition orbitals for the S0 → S1 transition. Subtle outcomes include the near orthogonal orientation of the π-planes of the bacteriochlorin macrocycles, and the substituent-induced shift in transition-dipole moment from the typical coincidence with the NH-NH axis; the two features together afforded the Förster orientation term κ2 ranging from 0.55-1.53 across the nine dyads, a value supportive of efficient excited-state energy transfer. The molecular design and collective insights on the dyads are valuable for studies relevant to artificial photosynthesis and other processes requiring ultrafast energy transfer.

Graphdiyne oxide elicits a minor foreign-body response and generates quantum dots due to fast degradation.

Graphdiyne (GDY) is a novel two-dimensional (2D) carbon allotrope that has attracted much attention in materials, physics, chemistry, and microelectronics for its excellent properties. Much effort has been devoted to exploring the biomedical applications of GDY in 2D carbon nanomaterials, especially for smart drugs and gene delivery. However, few studies have focused on the biocompatibility and potential environmental hazards of GDY and its derivatives. In this study, graphdiyne oxide (GDYO) and graphene oxide (GO) were obtained using different oxidation methods. Their cytotoxicity and hemolysis in vitro and biocompatibility in subcutaneous and peritoneal locations in vivo were compared. GDYO had very low biotoxicity in vitro and was moderately biocompatible in the muscle and abdominal cavity in vivo. Highly oxidized products and graphdiyne quantum dots (GDQDs) were observed in peritoneal cells. GDYO had better biocompatibility and its sheet size was easily diminished through oxidative degradation. Therefore, GDYO is a good candidate for use in 2D carbon nanomaterials in biomedicine.

Balancing Panchromatic Absorption and Multistep Charge Separation in a Compact Molecular Architecture.

A panchromatic triad and a charge-separation unit are joined in a crossbar architecture to capture solar energy. The panchromatic-absorber triad (T) is comprised of a central free-base porphyrin that is strongly coupled via direct ethyne linkages to two perylene-monoimide (PMI) groups. The charge-separation unit incorporates a free-base or zinc chlorin (C or ZnC) as a hole acceptor (or electron donor) and a perylene-diimide (PDI) as an electron acceptor, both attached to the porphyrin via diphenylethyne linkers. The free-base porphyrin is common to both light-harvesting and charge-separation motifs. The chlorin and PDI also function as ancillary light absorbers, complementing direct excitation of the panchromatic triad to produce the discrete lowest excited state of the array (T*). Attainment of full charge separation across the pentad entails two steps: (1) an initial excited-state hole/electron-transfer process to oxidize the chlorin (and reduce the panchromatic triad) or reduce the PDI (and oxidize the panchromatic triad); and (2) subsequent ground-state electron/hole migration to produce oxidized chlorin and reduced PDI. Full charge separation for pentad ZnC-T-PDI to generate ZnC+-T-PDI- occurs with a quantum yield of ∼30% and mean lifetime ∼1 µs in dimethyl sulfoxide. For C-T-PDI, initial charge separation is followed by rapid charge recombination. The molecular designs and studies reported here reveal the challenges of balancing the demands for charge separation (linker length and composition, excited-state energies, redox potentials, and medium polarity) with the constraints for panchromatic absorption (strong electronic coupling of the porphyrin and two PMI units) for integrated function in solar-energy conversion.

Probing the Effects of Electronic-Vibrational Resonance on the Rate of Excited-State Energy Transfer in Bacteriochlorin Dyads.

The impact of vibrational-electronic resonances on the rate of excited-state energy transfer is examined in a set of bacteriochlorin dyads that employ the same phenylethyne linker. The donor/acceptor excited-state energy gap is tuned from ∼200 to ∼1100 cm-1 using peripheral substituents on the donor and acceptor bacteriochlorin macrocycles. Ultrafast energy transfer is observed with rate constants of (0.3 ps)-1 to (1.7 ps)-1, which agree with those predicted by Förster theory to within a factor of 2. Furthermore, the measured rates follow a trend-line with only small deviations that do not correlate with the density of vibrations at the donor/acceptor excited-state energy gap. Thus, if vibrational-electronic resonances occur in any of these dyads, which seems likely, the impact on the rate of energy transfer is small.

How Best to Play the Role of Tumor Deposits in Stage III Colon Cancer?

Background: The purpose of this study is to comprehensively evaluate the prognostic role of tumor deposits (TD) in stage III colon cancer. Methods: 24,600 CC patients with III stage colon cancer were collected from the Surveillance, Epidemiology, and End Result (SEER) database and 618 CC patients from the Second Affiliated Hospital of Harbin Medical University. All patients were divided into development, internal, and external validation cohorts. The combination of positive lymph nodes (PLN) and the status or number of TD was defined as modified pN (mpN) and novel pN (npN). The Cox proportional hazard regression model was used to analyze the relationship between cancer-specific survival (CSS) and mpN or npN. CSS stratified by pN, mpN, and npN was analyzed by the Kaplan-Meier curves. The area under the receiver operating characteristic curve (AUC) was used to demonstrate the predictive abilities of the pN, mpN, and npN stages. The validation cohorts were used to validate the results. Results: The Cox proportional hazard regression model showed that mpN and npN were an independent prognostic factor for CSS. AUC showed that the predictive accuracy of mpN was better than that of the pN stage for 5-year CSS in the development (0.621 vs. 0.609, p < 0.001) and internal validation cohorts (0.618 vs. 0.612, p = 0.016) and the npN was also better than the pN stage for 5-year CSS in the development (0.623 vs. 0.609, p < 0.001) and internal validation cohorts (0.620 vs. 0.612, p = 0.001). However, there was no significant difference between the AUCs of mpN and npN. Moreover, the pN stage for 5-year CSS in the external validation cohort is 0.606 vs. 0.563, p = 0.045. Conclusions: In stage III CC, mpN and npN may be superior to the pN stage in assessing prognosis, suggesting that the TD information should be included in the pN stage.

Effect of Prophylactic Central Lymph Node Dissection on Locoregional Recurrence in Patients with Papillary Thyroid Microcarcinoma.

There is a consensus that central compartment lymph node dissection or modified radical lateral neck dissection should be performed in papillary thyroid microcarcinoma (PTMC) patients with lymph node metastases. Prophylactic central lymph node dissection (PCLND) in patients with clinically node-negative (cN0) PTMC to reduce locoregional recurrence (LRR) rate and improve prognosis remains controversial. The present study aimed to analyze the effect of PCLND on LRR and postoperative complications of PTMC in cN0 patients. We reviewed a cohort of patients with cN0 PTMC who underwent surgery between January 1997 and October 2019. The patients were divided into the PCLND and no lymph node dissection (NLND) groups. Kaplan-Meier curves were constructed to estimate 15-year locoregional recurrence-free survival rate of the two groups, and the difference was compared by the log-rank test. Three Cox regression models were performed to evaluate the correlation between PCLND and LRR. All patients underwent thyroidectomy, and 25 patients developed LRR; of whom, 23 underwent PCLND at initial surgery and 2 went without lymph node dissection. Cox regression analysis showed that PCLND had no effect on LRR. Postoperative hematoma and permanent recurrent laryngeal nerve injury did not occur in the NLND group, and their incidences were 0.5% and 0.3% in the PCLND group, respectively. PCLND had no significant correlation with LRR in patients with cN0 PTMC, and the absolute benefit for PTMC was small.

Evaluation of Risk Factors for Bleeding After Ultrasound-Guided Liver Biopsy.

PURPOSE: This study was performed to analyze the risk factors for hemorrhagic complications after ultrasound-guided liver biopsies. PATIENTS AND METHODS: In this retrospective study, we reviewed 1193 ultrasound-guided percutaneous liver biopsies performed in our hospital from January 2018 to December 2020. Relevant patient characteristics, indications for biopsy, laboratory findings, biopsy technique, hemorrhagic complications, and pathologic outcomes were collected. RESULTS: We analyzed 834 procedures performed on 807 patients with complete data. The bleeding group comprised 45 patients with post-procedure bleeding, and non-bleeding group comprising the remaining 789 patients. Univariate analysis showed that age (p < 0.001), number of needle passes (p = 0.009), platelet count (p = 0.002), prothrombin time (p < 0.001), and international normalized ratio (p < 0.001) were associated with post-procedure bleeding. Multivariable regression analysis showed that age under 18 years (p < 0.001), low platelet count (p = 0.001), and increased needle passes (p = 0.025) were independent risk factors for bleeding complications. CONCLUSION: Sex and focal liver lesions did not affect the risk of post-procedure bleeding. The international normalized ratio and prothrombin time were associated with an increased incidence of bleeding; however, they had no predictive value. Age, number of needle passes, and platelet count were identified as reliable predictors of bleeding.

Chaperonin-Containing TCP1 Subunit 6A Is a Prognostic Potential Biomarker That Correlates With the Presence of Immune Infiltrates in Colorectal Cancer.

AIMS: Chaperonin-containing TCP1 subunit (CCT) 6A is an oncogenic 6th subunit of the CCT family. Nevertheless, not much is documented regarding its function in colorectal cancer (COAD). This investigation seeks to explore the role of CCT6A in the prognosis of COAD. MAIN METHODS: Sequencing data from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas database (TCGA) were employed to analyze the expression of CCT6A and its involvement in various regulatory networks behind COAD. Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) analyzed Levels of expression and survival rates, while GEPIA was used to uncover further the functional networks that involved CCT6A. Database for Annotation, Visualization, and Integrated Discovery (DAVID) tools were used to interpret Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Evaluation of the expression levels of CCT6A in COAD samples was also verified via immunohistochemistry. KEY FINDINGS: We found that the expression of CCT6A is up-regulated in COAD. CCT6A correlated with poor prognosis and decreased immune infiltrates such as CD4+ T cells, B cells, and dendritic cells. CCT6A is increased in COAD patients. CCT6A is associated with several gene networks related to the DDX family and mismatch repair pathways. SIGNIFICANCE: Our data showed that data mining was able to uncover data regarding levels of CCT6A and its involvement in genetic regulating pathways in COAD.

Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis.

BACKGROUND: Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. METHODS: ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. RESULTS: We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. CONCLUSION: In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.