Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Clinical outcomes of percutaneous microwave ablation for pulmonary oligometastases from hepatocellular carcinoma: a retrospective, multicenter study.

BACKGROUND: Pulmonary oligometastases are common in hepatocellular carcinoma (HCC), however, the existing therapeutic options have several limitations. This study aimed to assess the safety and efficacy of microwave ablation (MWA) in the treatment of HCC-originating pulmonary oligometastases. METHODS: A total of 83 patients, comprising 73 males and 10 females with a median age of 57 years, who had pulmonary oligometastases from HCC, underwent MWA treatment at four different medical institutions. Inclusion criteria for patients involved having primary HCC under control and having less than three oligometastases with a maximum diameter of ≤ 5 cm in the unilateral lung or less than five oligometastases with a maximum diameter of ≤ 3 cm in the bilateral lung. A total of 147 tumors were treated with MWA over 116 sessions. The primary endpoints assessed included technical success, treatment efficacy, and local progression rate, while secondary endpoints encompassed complications, clinical outcomes, overall survival (OS), local progression-free survival (LPFS), and prognostic factors. RESULTS: The technical success rate for MWA was 100% (116/116 sessions), and the treatment efficacy rate was 82.3% (121/147 tumors). Six months after MWA, the local progression rate was 23.1% (18/147 tumors). Complications were observed in 10.3% (major) and 47.4% (minor) of the 116 sessions, with no cases of ablation-related deaths. The median follow-up period was 21.6 months (range: 5.7-87.8 months). Median OS was 22.0 months, and the 1-, 2-, and 3-year OS rates were 82.6%, 44.5%, and 25.2%, respectively. Median LPFS was 8.5 months. Multivariate Cox regression analysis identified α-fetoprotein (AFP) levels during initial diagnosis and the number of oligometastases as potential independent prognostic factors for OS (p = 0.017 and 0.045, respectively). CONCLUSION: Percutaneous MWA is a safe and effective treatment modality for pulmonary oligometastases originating from HCC.

MeIS: DNA methylation-based immune response signatures for thyroid nodule diagnostics.

CONTEXT: Accurately distinguishing between benign thyroid nodules (BTNs) and papillary thyroid cancers (PTCs) with current conventional methods poses a significant challenge. OBJECTIVE: We identify DNA methylation markers of immune response-related genes for distinguishing BTNs and PTCs. METHODS: In this study, we analyzed a public reduced representative bisulfite sequencing (RRBS) dataset and revealed distinct methylation patterns associated with immune signals in PTCs and BTNs. Based on these findings, we developed a diagnostic classifier named as the Methylation-based Immune Response Signature (MeIS), which was composed of fifteen DNA methylation markers associated with immune response-related genes. We validated the MeIS's performance in two independent cohorts: ZS's retrospective cohort (50 PTC and 18 BTN surgery-leftover samples) and ZS's preoperative cohort (31 PTC and 30 BTN fine-needle aspiration (FNA) samples). RESULTS: The MeIS classifier demonstrated significant clinical promise, achieving AUCs of 0.96, 0.98, 0.89 and 0.90 in the training set, validation set, ZS's retrospective cohort, and ZS's preoperative cohort, respectively. For the cytologically indeterminate thyroid nodules, in the ZS's retrospective cohort, MeIS exhibited a sensitivity of 91% and a specificity of 82%; in the ZS's preoperative cohort, MeIS achieved a sensitivity of 84% and a specificity of 74%. Additionally, combining MeIS and BRAFV600E detection improved the detecting performance of cytologically indeterminate thyroid nodules, yielding sensitivities of 98% and 87%, and specificities of 82% and 74% in the ZS's retrospective cohort and ZS's preoperative cohort, respectively. CONCLUSIONS: The fifteen markers we identified can be employed to improve the diagnostic of cytologically indeterminate thyroid nodules.

Reactive lymphoid hyperplasia of the liver: A rare case report.

BACKGROUND: Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign lymphoproliferative lesion and a poorly understood disease. It is usually asymptomatic and incidental, but it is difficult to distinguish from hepatocellular carcinoma and metastatic liver tumor on imaging, and percutaneous biopsy is not sufficient to distinguish from low-grade malignant lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), making diagnosis difficult. CASE SUMMARY: A 69-year-old woman came to our hospital for reexamination of pulmonary nodules followed by liver occupation. The lesions showed "wash-in and wash-out" on contrast-enhanced ultrasonography and magnetic resonance imaging. Enhanced magnetic resonance also showed annular envelope enhancement and limited diffusion on the ADC map during the delay period. Imaging revealed metastatic liver cancer, and the patient underwent a partial hepatectomy. However, the final histopathological diagnosis was RLH. CONCLUSION: If small isolated nodules are found in the liver of middle-aged and elderly female patients with no risk factors for liver malignancy, when the enhanced imaging suggests "wash-in and wash-out", further focus should be placed on whether the enhanced imaging shows perinodular enhancement and whether the DWI shows limited diffusion in MRI, in order to emphasize the possibility of liver RLH diagnosis.

Correlation analysis of MR elastography and Ki-67 expression in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver cancer with dismal outcome, high Ki-67 expression is associated with active progression and poor prognosis of iCCA, the application of MRE in the prediction of iCCA Ki-67 expression has not yet been investigated until now. We aimed to evaluate the value of magnetic resonance elastography (MRE) in assessing Ki-67 expression for iCCA. RESULTS: In the whole cohort, 97 patients (57 high Ki-67 and 40 low Ki-67; 58 males, 39 females; mean age, 58.89 years, ranges 36-70 years) were included. At the multivariate analysis, tumor stiffness (odds ratio (OR) = 1.669 [95% CI: 1.307-2.131], p < 0.001) and tumor apparent diffusion coefficient (ADC) (OR = 0.030 [95% CI: 0.002, 0.476], p = 0.013) were independent significant variables associated with Ki-67. Areas under the curve of tumor stiffness for the identification of high Ki-67 were 0.796 (95% CI 0.702, 0.871). Tumor stiffness was moderately correlated with Ki-67 level (r = 0.593, p < 0.001). When both predictive variables of tumor stiffness and ADC were integrated, the best performance was achieved with area under the curve values of 0.864 (95% CI 0.780-0.926). CONCLUSION: MRE-based tumor stiffness correlated with Ki-67 in iCCA and could be investigated as a potential prognostic biomarker. The combined model incorporating both tumor stiffness and ADC increased the predictive performance. CRITICAL RELEVANCE STATEMENT: MRE-based tumor stiffness might be a surrogate imaging biomarker to predict Ki-67 expression in intrahepatic cholangiocarcinoma patients, reflecting tumor cellular proliferation. The combined model incorporating both tumor stiffness and apparent diffusion coefficient increased the predictive performance. KEY POINTS: • MRE-based tumor stiffness shows a significant correlation with Ki-67. • The combined model incorporating tumor stiffness and apparent diffusion coefficient demonstrated an optimized predictive performance for Ki-67 expression. • MRE-based tumor stiffness could be investigated as a potential prognostic biomarker for intrahepatic cholangiocarcinoma.

Comparison of intraluminal brachytherapy combined with and without stent placement for treatment of obstructive jaundice induced by tumor thrombus.

PURPOSE: To compare the safety and efficacy of intraluminal brachytherapy with iodine-125 (125I) seed strand implantation combined with and without stent placement to treat patients with obstructive jaundice induced by tumor thrombus. METHODS: Between January 2018 and June 2022, 42 patients with malignant obstructive jaundice (MOJ) induced by tumor thrombus were included. 20 patients received 125I seed strand implantation and stent placement (group A). The remaining 22 patients, implanted 125I seed strands only, served as control (group B). The two groups' overall survival and jaundice-free survival were compared using the Kaplan-Meier method and log-rank test. RESULTS: During the follow-up period, the mean survival time of group A was 38.0 ± 4.1 months (95%CI, 30.0-46.1 months), while that of group B was 25.1 ± 2.8 (95% CI, 19.5-30.6 months) (p = 0.406). The mean survival rates of 12 months for all patients, group A, and group B was 66.7%, 65%, and 68%, respectively. The mean jaundice-free survival of group A and group B were 34.0 ± 3.6 months (95% CI, 27.9-41.2months) and 22.9 ± 2.7 months (95%CI, 17.5-28.2months) (p = 0.254), respectively. Two PTBD drainage tube infection cases occurred in group A and group B separately. CONCLUSIONS: 125I intraluminal brachytherapy is an effective and safe therapy for treating patients with obstructive jaundice induced by tumor thrombus.

Preliminary radiogenomic study of hepatitis B virus-related hepatocellular carcinoma: associations between MRI features and mutations.

Aim: To investigate associations between MRI features and high-frequency mutations of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: This study included 58 HCC patients who underwent contrast-enhanced MRI prior to surgical resection and genome sequencing. MRI features and mutation information were evaluated. Results: The top five most frequently mutated genes in HCC were TP53 (53.45%), TAF1 (24.14%), PDE4DIP (22.41%), ABCA13 (18.97%) and LRP1B (17.24%). Mutations in TP53 and LRP1B were associated with tumor necrosis (p = 0.035) and mosaic architecture (p = 0.015), respectively. Mutations in ABCA13 were associated with mosaic architecture (p = 0.025) and necrosis (p = 0.010). Conclusion: This preliminary radiogenomics analysis showed associations between MRI features and high-frequency mutations in HBV-related HCCs.

Radiogenomics has been helpful for disease prevention, diagnosis, treatment, prognosis and drug development, and has shown good prospects in gene function analysis and gene therapy research. Some studies have explored the relationship between the underlying genotype and MRI features. However, few studies have indicated the relationship between the underlying genotype and MRI features of hepatocellular carcinoma (HCC) so far. In this study, the top five most frequently mutated genes in hepatitis B virus-related HCCs were TP53, TAF1, PDE4DIP, ABCA13 and LRP1B and certain associations existed between MRI features and high-frequency mutations. These results demonstrated the potential clinical value of imaging traits as surrogate markers of molecular portraits in HCC. The potential correlations between MRI features and high-frequency mutations may provide effective clinical information for hepatitis B virus-related HCCs.

The prognostic role of the AST/ALT ratio in hepatocellular carcinoma patients receiving thermal ablation combined with simultaneous TACE.

BACKGROUND: To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. METHODS: The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. RESULTS: The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600-0.748). CONCLUSIONS: The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.

Assessment of an MR Elastography-Based Nomogram as a Potential Imaging Biomarker for Predicting Microvascular Invasion of Hepatocellular Carcinoma.

BACKGROUND: Microvascular invasion (MVI) is a well-established poor prognostic factor for hepatocellular carcinoma (HCC). Preoperative prediction of MVI is important for both therapeutic and prognostic purposes, but noninvasive methods are lacking. PURPOSE: To develop an MR elastography (MRE)-based nomogram for the preoperative prediction of MVI in HCC. STUDY TYPE: Prospective. SUBJECTS: A total of 111 patients with surgically resected single HCC (52 MVI-positive and 59 MVI-negative), randomly allocated to training and validation cohorts (7:3 ratio). FIELD STRENGTH/SEQUENCE: 2D-MRE and conventional sequences (T1-weighted in-phase and opposed phase gradient echo, T2-weighted fast spin echo, diffusion-weighted single-shot spin echo echo-planar, and dynamic contrast-enhanced T1-weighted gradient echo) at 3.0 T. ASSESSMENT: MRE-stiffness and conventional qualitative and quantitative MRI features were evaluated and compared between MVI-positive and MVI-negative HCCs. STATISTICAL TESTS: Univariable and multivariable logistic regression analyses were applied to identify potential predictors for MVI, and a nomogram was constructed according to the predictive model. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. Harrell's C-index evaluated the discrimination performance of the nomogram, calibration curves analyzed its diagnostic performance and decision curve analysis determined its clinical usefulness. A P value <0.05 was considered statistically significant. RESULTS: Tumor stiffness >6.284 kPa (odds ratio [OR] = 24.38) and the presence of arterial peritumoral enhancement (OR = 6.36) were independent variables associated with MVI. The areas under the ROC curves for tumor stiffness were 0.81 (95% confidence interval [CI]: 0.70, 0.89) and 0.77 (95% CI: 0.60, 0.90) in the training and validation cohorts, respectively. When both predictive variables were integrated, the best nomogram performance was achieved with C-indices of 0.88 (95% CI: 0.78, 0.94) and 0.87 (95% CI: 0.71, 0.96) in the two cohorts, fitting well in calibration curves. The decision curve exhibited optimal net benefit with a wide range of threshold probabilities for the nomogram. DATA CONCLUSION: An MRE-based nomogram may be a potential noninvasive imaging biomarker for predicting MVI of HCC preoperatively. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Corrigendum: Comparison of clinical outcomes between cone beam CT-guided thermal ablation and helical tomotherapy in pulmonary metastases from hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.947284.].

Comparison of clinical outcomes between cone beam CT-guided thermal ablation and helical tomotherapy in pulmonary metastases from hepatocellular carcinoma.

Objective: This retrospective study compares the clinical results of cone beam CT (CBCT)-guided thermal ablation with those of helical tomotherapy in hepatocellular carcinoma (HCC) patients with pulmonary metastases. Methods: A total of 110 patients undergoing thermal ablation or helical tomotherapy for pulmonary metastases from April 2014 to December 2020 were included in the study. The endpoints were local tumor progression-free survival (LTPFS), overall survival (OS), and complications. Univariate and multivariate analyses using the Cox proportional hazard model were conducted to identify independent factors (univariate: P < 0.1; multivariate: P < 0.05). The Kaplan-Meier method was used to calculate the LTPFS and OS rates. Results: The results of 106 patients were taken into the final analysis. The 1- and 3-year LTPFS rates were 50 and 19% for the thermal ablation group and 65 and 25% for the helical tomotherapy group. The median LTPFS in the thermal ablation group was 12.1 months, while it was 18.8 months in the helical tomotherapy group (P = 0.25). The 1- and 3-year OS rates were 75 and 26% for the thermal ablation group and 77 and 37% for the helical tomotherapy group. The median OS was 18.0 months in the thermal ablation group and 23.4 months in the helical tomotherapy group (P = 0.38). The multivariate analyses found that α-fetoprotein (AFP) at <400 ng/ml (P = 0.003) was significantly associated with better LTPFS. Tumor number <3 and AFP <400 ng/ml were favorable prognostic factors for OS. There were no grades 3-5 adverse events in both groups. Grade 2 was recorded in three patients (4.8%) in the thermal ablation group and two patients (4.7%) in the helical tomotherapy group. Conclusions: For pulmonary metastases from HCC, CBCT-guided thermal ablation and helical tomotherapy provided comparable clinical effects and safety.

Microwave ablation combined with lipiodol-microsphere mixed or conventional transarterial chemoembolization for the treatment of colorectal liver metastases: A retrospective study.

PURPOSE: To investigate the clinical outcomes of microwave ablation (MWA) combined with lipiodol-microsphere mixed transarterial chemoembolization (mTACE) or conventional TACE (cTACE) for patients with colorectal liver metastases (CRLM). MATERIALS AND METHODS: This retrospective study evaluated the medical records of patients with CRLM who underwent MWA combined with mTACE or cTACE from January 2018 to September 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated during the follow-up. In addition, prognostic factors affecting survival were analyzed by univariate and multivariate methods. RESULTS: A total of 79 patients with CRLM were enrolled in the study (MWA-mTACE group, n = 38; MWA-cTACE group, n = 41). The patients who underwent MWA-mTACE had higher DCR (86.8% vs. 65.9%, P = 0.029) and better PFS (median, 8.1 vs. 5.5 months, P = 0.018) than those who underwent MWA-cTACE, but no significant difference was found in ORR (34.2% vs. 22.0%, P = 0.225) and OS (median, 15.7 vs. 13.0 months, P = 0.231). Further univariate and multivariate analyses indicated that MWA-mTACE was an independent positive factor for PFS, and abnormal carcinoembryonic antigen level was a hazard factor for OS. The postoperative laboratory tests and complications in patients who underwent MWA-mTACE were similar to those who underwent MWA-cTACE. CONCLUSION: Lipiodol-microsphere mixed TACE might be an effective and safe treatment to combine with microwave ablation for patients with colorectal liver metastases.

Application of contrast-enhanced ultrasound in minimally invasive ablation of benign thyroid nodules.

Objective: This study aimed to investigate the application value of contrast-enhanced ultrasound (CEUS) before and after minimally invasive ablation procedures for benign thyroid nodule(s) (BTN). Methods: This prospective study included patients with BTNs scheduled to undergo ultrasound-guided minimally invasive ablation treatment. CEUS was performed before and after ablation (at 1 day, and 1, 6, and 12 months after ablation). Changes in microvascular perfusion and the volume of BTNs were noted and assessed. Results: Sixty-two patients (62 BTNs), who underwent ablation procedures between June 2016 and August 2020, were included. All lesions were confirmed by biopsy, and histopathological results were obtained before ablation treatment. On preoperative CEUS, the lesions exhibited hyperenhancement (53.23%) or iso-enhancement (46.77%) during the arterial phase, and all lesions exhibited iso-enhancement in the venous and late phases. One day after ablation, none of the BTNs exhibited obvious enhancement on CEUS. One (1.61%) lesion was re-treated due to a nodule-like enhancement area detected by CEUS at the 6-month follow-up. The mean nodular volume reduction rate (VRR) at 1, 6, and 12 months follow-up demonstrated no significant difference between the two ablation groups (microwave ablation versus radiofrequency ablation). Twelve months after ablation, the mean (±SD) VRR of all BTNs was 60.3 â€‹± â€‹10.3%. Conclusion: CEUS helped guide treatment decisions for BTNs before ablation treatment. Moreover, it could also be used to accurately and noninvasively evaluate treatment efficacy.