Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

Integrated analysis of DNA methylome and transcriptome revealing epigenetic regulation of CRIR1-promoted cold tolerance.

BACKGROUND: DNA methylation contributes to the epigenetic regulation of nuclear gene expression, and is associated with plant growth, development, and stress responses. Compelling evidence has emerged that long non-coding RNA (lncRNA) regulates DNA methylation. Previous genetic and physiological evidence indicates that lncRNA-CRIR1 plays a positive role in the responses of cassava plants to cold stress. However, it is unclear whether global DNA methylation changes with CRIR1-promoted cold tolerance. RESULTS: In this study, a comprehensive comparative analysis of DNA methylation and transcriptome profiles was performed to reveal the gene expression and epigenetic dynamics after CRIR1 overexpression. Compared with the wild-type plants, CRIR1-overexpressing plants present gained DNA methylation in over 37,000 genomic regions and lost DNA methylation in about 16,000 genomic regions, indicating a global decrease in DNA methylation after CRIR1 overexpression. Declining DNA methylation is not correlated with decreased/increased expression of the DNA methylase/demethylase genes, but is associated with increased transcripts of a few transcription factors, chlorophyll metabolism and photosynthesis-related genes, which could contribute to the CRIR1-promoted cold tolerance. CONCLUSIONS: In summary, a first set of transcriptome and epigenome data was integrated in this study to reveal the gene expression and epigenetic dynamics after CRIR1 overexpression, with the identification of several TFs, chlorophyll metabolism and photosynthesis-related genes that may be involved in CRIR1-promoted cold tolerance. Therefore, our study has provided valuable data for the systematic study of molecular insights for plant cold stress response.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

Feeding artery: a valuable feature for differentiation of regenerative nodule, dysplastic nodules and small hepatocellular carcinoma in CEUS LI-RADS.

OBJECTIVE: To investigate whether the feeding artery (FA) feature can aid in discriminating small hepatocellular carcinoma (HCC) using the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) from precancerous lesions. METHODS: Between June 2017 and May 2021, a total of 347 patients with 351 precancerous liver lesions or small HCCs who underwent CEUS were enrolled. Two independent radiologists assigned LI-RADS categories to all lesions and assessed the presence of the FA feature, which was used as an ancillary feature to either upgrade or downgrade the LI-RADS category. The diagnostic performance of CEUS LI-RADS, both with and without the FA feature, was evaluated based on accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The FA feature was found to be more prevalent in HCC (85.54%, p < 0.001) than in regenerative nodules (RNs, 29.73%), low-grade dysplastic nodules (LGDNs, 33.33%), and high-grade dysplastic nodules (HGDNs, 55.26%). Furthermore, the presence of arterial phase hyperenhancement (APHE), washout (WO), and FA in liver nodules was associated with a higher expression of GPC-3 and Ki-67 compared to the group without these features (p < 0.001). After adjusting, the sensitivity and accuracy of LR-5 for HCC improved from 68.67% (95%CI: 62.46%, 74.30%) to 77.51% (95%CI: 71.72%, 82.44%) and from 69.23% (95%CI: 64.11%, 74.02%) to 73.79% (95%CI: 68.86%, 78.31%), respectively. CONCLUSION: The FA feature is a valuable feature for distinguishing small HCC and precancerous lesions and could be added as a possible ancillary feature in CEUS LI-RADS which was backed up by biomarkers. CLINICAL RELEVANCE STATEMENT: The presence of a feeding artery is a valuable imaging feature in the differentiation of HCC and precancerous lesions. Incorporating this characteristic in the CEUS LI-RADS can enhance the diagnostic ability. KEY POINTS: • Feeding artery is more frequent in HCC than in regenerative nodules, low-grade dysplastic nodules, and high-grade dysplastic nodules. • Feeding artery feature is a valuable ancillary feature for CEUS LI-RADS to differentiate regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, and HCC. • The existence of feeding artery, arterial phase hyperenhancement, and washout is associated with more GPC-3 positive expression and higher Ki-67 expression than the group without these features.

Ultrasound-guided microwave ablation versus surgery for solitary T1bN0M0 papillary thyroid carcinoma: a prospective multicenter study.

OBJECTIVE: Microwave ablation (MWA) has emerged as a minimally invasive technology for papillary thyroid microcarcinoma (PTMC), but it has not been widely applied to treat T1bN0M0 PTC with high-level evidence. This study was designed to compare the real-world efficacy and safety of MWA or surgery for treating T1bN0M0 PTC. METHODS: From December 2019 to April 2021, 123 continuous unifocal T1bN0M0 PTC patients without lymph node metastasis (LNM) or distant metastasis (DM) were included from 10 hospitals. Patients were allocated into the MWA or surgery group based on their willingness. The main outcomes were local tumour progression (LTP), new thyroid cancer, LNM, and DM. The secondary outcomes included changes in tumour size and volume, complications, and cosmetic results. Subgroup analyses were conducted to identify influencing factors. RESULTS: Fifty-two patients chose MWA, and 71 patients chose surgery. Patients had similar demographic information and tumour characteristics in the two groups. The follow-up durations after MWA and surgery were 10.6 ± 4.2 and 10.4 ± 3.4 months, respectively. The LNM rate was 5.8% in the MWA group and 1.4% in the surgery group (p = 0.177). No LTP, new thyroid cancer, or distant metastasis (DM) occurred in either group. Five (9.6%) of the 52 patients in the MWA group and 8 (11.3%) of the 71 patients in the surgery group had complications (p = 0.27). Better cosmetic results were found in the MWA group (p < 0.01). CONCLUSION: MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. CLINICAL RELEVANCE STATEMENT: MWA achieved comparable short-time treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC. KEY POINTS: • MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. • The complication rate in the surgery group was higher than that in the MWA group without a significant difference. • There was no statistically significant difference in the LNM rate between the MWA and surgery groups.

Ultrasound-guided percutaneous microwave ablation for metabolic-associated fatty liver disease-related hepatocellular carcinoma (HCC) versus hepatitis virus B-related HCC: a propensity score matching study.

OBJECTIVES: To compare the long-term outcomes of microwave ablation (MWA) for primary hepatocellular carcinoma (HCC) in patients with metabolic-associated fatty liver disease (MAFLD) with those infected by hepatitis virus B (HBV). METHODS: The clinical data of HCC patients under the treatment of MWA were analyzed retrospectively between 2010 and 2021 at Chinese PLA General Hospital. Patients were divided into MAFLD-HCC and HBV-HCC group according to the chronic liver disease etiology. The propensity score matching (PSM) was performed to reduce the interference of confounders. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), cancer-specific survival (CSS) and intrahepatic distant recurrence (IDR). RESULTS: A total of 648 patients (age range, 18-91 years) with 1019 lesions were enrolled including 601 with HBV-HCC and 47 with MAFLD-HCC. After a variable ratio of 1:n ≤ 4 PSM, 100 patients were included in the HBV-HCC and 41 in the MAFLD-HCC group. No statistical differences in OS and CSS (p = 0.880 and p = 0.980, respectively) were observed between the two groups in the matched cohort, while MAFLD-HCC exhibited better RFS and lower IDR rates compared to HBV-HCC (p = 0.043 and p = 0.041, respectively). Additionally, MAFLD-HCC generated lower ascending range in the liver function indexes like ΔALT (46.7 vs. 98.5, p < 0.001), ΔTBIL (1.9 vs. 7.5, p = 0.001) and ΔAST (38.1 vs. 148.6, p < 0.001) than HBV-HCC after MWA. CONCLUSIONS: MWA is an effective treatment for HCC patients with MAFLD. The recurrence prognosis of MAFLD-HCC was better than HBV-HCC and the degree of liver injury after MWA was lower.

MAFLD-HCC exhibited better recurrence-free survival and lower intrahepatic distance metastasis rates compared with HBV-HCC (p = 0.043 and p = 0.041, respectively).MAFLD-HCC generated lower ascending range in the liver function indexes than HBV-HCC after MWA on the first day.After PSM, MAFLD-HCC displayed better prognosis on recurrence-free survival and intrahepatic distance recurrence in almost all subgroups.

Percutaneous microwave ablation versus sclerotherapy for large hepatic hemangioma: a multi-center cohort study.

OBJECTIVE: The study aimed to compare the effectiveness and safety of ultrasound-guided microwave ablation (MWA) and percutaneous sclerotherapy (PS) for the treatment of large hepatic hemangioma (LHH). METHODS: This retrospective study included 96 patients who underwent MWA (n = 54) and PS (n = 42) as first-line treatment for LHH in three tertiary hospitals from January 2016 to December 2021. Primary outcomes were technique efficacy rate (volume reduction rate [VRR] > 50% at 12 months), symptom relief rate at 12 months and local tumor progression (LTP). Secondary outcomes included procedure time, major complications, treatment sessions, cost and one-, two-, three-year VRR. RESULTS: During a median follow-up of 36 months, the MWA group showed a higher technique efficacy rate (100% vs. 90.4%, p = .018) and symptom relief rate (100% vs. 80%, p = .123) than the PS group. The MWA group had fewer treatment sessions, higher one-, two- and three-year VRR, lower LTP rate (all p < .05), longer procedure time and higher treatment costs than the PS group (both p < .001). MWA shared a comparable major complications rate (1.8% vs. 2.4%, p = .432) with PS. After multivariate analysis, the lesion's heterogeneity and maximum diameter >8.1 cm were independent risk factors for LTP (all p < .05). In the PS group, lesions with a cumulative dose of bleomycin > 0.115 mg/cm3 had a lower risk of LTP (p = .006). CONCLUSIONS: Both MWA and PS treatments for large hepatic hemangioma are safe and effective, with MWA being superior in terms of efficacy.

Biological function research of Fusarium oxysporum f. sp. cubense inducible banana long noncoding RNA Malnc2310 in Arabidopsis.

Long noncoding RNAs (lncRNAs) participate in plant biological processes under biotic and abiotic stresses. However, little is known about the function and regulation mechanism of lncRNAs related to the pathogen at a molecular level. A banana lncRNA, Malnc2310, is a Fusarium oxysporum f. sp. cubense inducible lncRNA in roots. In this study, we demonstrate the nuclear localization of Malnc2310 by fluorescence in situ hybridization and it can bind to several proteins that are related to flavonoid pathway, pathogen response and programmed cell death. Overexpression of Malnc2310 increases susceptibility to Fusarium crude extract (Fu), salinity, and cold in transgenic Arabidopsis. In addition, Malnc2310 transgenic Arabidopsis accumulated more anthocyanins under Fusarium crude extract and cold treatments that are related to upregulation of these genes involved in anthocyanin biosynthesis. Based on our findings, we propose that Malnc2310 may participate in flavonoid metabolism in plants under stress. Furthermore, phenylalanine ammonia lyase (PAL) protein expression was enhanced in Malnc2310 overexpressed transgenic Arabidopsis, and Malnc2310 may participate in PAL regulation by binding to it. This study provides new insights into the role of Malnc2310 in mediating plant stress adaptation.

Microwave Ablation for Papillary Thyroid Microcarcinoma with and without US-detected Capsule Invasion: A Multicenter Prospective Cohort Study.

Background Microwave ablation (MWA) has achieved favorable results in the treatment of papillary thyroid microcarcinoma (PTMC) confined in glandular parenchyma. However, studies on the outcome of MWA for PTMC with US-detected capsular invasion remain unclarified in the literature. Purpose To compare the feasibility, effectiveness, and safety of MWA in the treatment of PTMC with and without US-detected capsular invasion. Materials and Methods Participants from 12 hospitals with a PTMC maximal diameter of 1 cm or less without US- or CT-detected lymph node metastasis (LNM) who planned to undergo MWA were enrolled in this prospective study between December 2019 and April 2021. All tumors were evaluated with preoperative US and were divided into those with and those without capsular invasion. The participants were observed until July 1, 2022. The primary end points, including technical success and disease progression, and the secondary end points, including treatment parameters, complications, and tumor shrinkage during follow-up, were compared between the two groups, and multivariable regression was performed. Results After exclusion, 461 participants (mean age, 43 years ± 11 [SD]; 337 women) were included: 83 with and 378 without capsular invasion. After one participant with capsular invasion aborted MWA because of technical failure, 82 participants with and 378 participants without capsular invasion (mean tumor volume, 0.1 mL ± 0.1 vs 0.1 mL ± 0.1; P = .07) were analyzed with a mean follow-up period of 20 months ± 4 (range, 12-25 months) and 21 months ± 4 (range, 11-26 months), respectively. In those with and those without capsular invasion, comparable technical success rates were achieved (99% [82 of 83] vs 100% [378 of 378], P = .18), with one and 11 complications, respectively (1% [one of 82] vs 3% [11 of 378], P = .38). There was no evidence of differences in disease progression (2% [one of 82] vs 1% [four of 378]; P = .82) or tumor shrinkage (mean, 97% ± 8 [SD] vs 96% ± 13; P = .58). Conclusion Microwave ablation was feasible in the treatment of papillary thyroid microcarcinoma with US-detected capsular invasion and showed comparable short-term efficacy with or without the presence of capsular invasion. © RSNA, 2023 Clinical trial registration no. NCT04197960 Supplemental material is available for this article.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Patients with metastatic renal cell carcinoma who receive immune-targeted therapy may derive survival benefit from nephrectomy.

BACKGROUND: Nephrectomy, whether in the era of cytokine therapy or targeted therapy, has an important role in the treatment of metastatic renal cell carcinoma. With the advent of immunotherapy, immunotherapy combined with targeted therapy has become the mainstream of systemic therapy, but the role of nephrectomy in metastatic renal cell carcinoma is unclear. In this study, we retrospectively analyzed the impact of nephrectomy on survival in patients with metastatic renal cell carcinoma who received immune-targeted therapy. METHODS: Patients with metastatic renal cell carcinoma who received immune-targeted therapy at three centers between May 17, 2019 and August 1, 2022 were collected, who were divided into two groups based on whether nephrectomy was performed or not. Survival, response rate and adverse event were compared between the two groups. The primary end point was progression free survival, Subgroup analysis and univariate and multivariable prognostic analyses were also assessed. RESULTS: With a median follow-up time of 29.3 months (95% CI 28.5-30.2), 165 patients were recruited and divided into two groups based on whether they underwent nephrectomy or not. There were 68 patients in the non-nephrectomy group, 97 in the nephrectomy group. Compared to patients treated with immune-targeted therapy, patients treated with immune-targeted therapy plus nephrectomy were able to achieve survival benefits, with a median PFS of 10.8 months (95% CI 8.3-13.3) and 14.4 months (95% CI 12.6-16.2), respectively, as well as an HR of 0.476 (95% CI 0.323-0.701, p = 0.0002). The 12-month and 18-month PFS rates were 30.9% versus 60.8% and 7.4% versus 25.8%, respectively. The objective response rate (ORR) was 52.9% and 60.8%, respectively, in the non-nephrectomy and nephrectomy groups (p = 0.313), and the disease control rate (DCR) was 75% and 83.5%, respectively (p = 0.179). The most common adverse events related to treatment were hypothyroidism, immune-related pneumonitis and rash. Multivariate analysis showed that primary tumor nephrectomy prior to immune-targeted therapy, clear cell renal carcinoma and oligo metastasis were independent prognostic factors. CONCLUSIONS: Nephrectomy may provide PFS benefit with tolerable safety for patients with metastatic renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors.

Deep learning model based on contrast-enhanced ultrasound for predicting early recurrence after thermal ablation of colorectal cancer liver metastasis.

OBJECTIVES: To develop and validate a deep learning (DL) model based on quantitative analysis of contrast-enhanced ultrasound (CEUS) images that predicts early recurrence (ER) after thermal ablation (TA) of colorectal cancer liver metastasis (CRLM). METHODS: Between January 2010 and May 2019, a total of 207 consecutive patients with CRLM with 13,248 slice images at three dynamic phases who received CEUS within 2 weeks before TA were retrospectively enrolled in two centres (153 for the training cohort (TC), 32 for the internal test cohort (ITC), and 22 for the external test cohort (ETC)). Clinical and CEUS data were used to develop and validate the clinical model, DL model, and DL combining with clinical (DL-C) model to predict ER after TA. The performance of these models was compared by the receiver operating characteristic curve (ROC) with the DeLong test. RESULTS: After a median follow-up of 56 months, 49% (99/207) of patients experienced ER. Three key clinical features (preoperative chemotherapy (PC), lymph node metastasis of the primary colorectal cancer (LMPCC), and T stage) were used to develop the clinical model. The DL model yielded better performance than the clinical model in the ETC (AUC: 0.67 for the clinical model, 0.76 for the DL model). The DL-C model significantly outperformed the clinical model and DL model (AUC: 0.78 for the DL-C model in the ETC; both, p < 0.001). CONCLUSIONS: The model based on CEUS can achieve satisfactory prediction and assist physicians during the therapeutic decision-making process in clinical practice. KEY POINTS: • This is an exploratory study in which ablation-related contrast-enhanced ultrasound (CEUS) data from consecutive patients with colorectal cancer liver metastasis (CRLM) were collected simultaneously at multiple institutions. • The deep learning combining with clinical (DL-C) model provided desirable performance for the prediction of early recurrence (ER) after thermal ablation (TA). • The DL-C model based on CEUS provides guidance for TA indication selection and making therapeutic decisions.

Analysis of Sonazoid contrast-enhanced ultrasound for predicting the risk of microvascular invasion in hepatocellular carcinoma: a prospective multicenter study.

OBJECTIVES: The aim of this study was to evaluate the potential of Sonazoid contrast-enhanced ultrasound (SNZ-CEUS) as an imaging biomarker for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: From August 2020 to March 2021, we conducted a prospective multicenter study on the clinical application of Sonazoid in liver tumor; a MVI prediction model was developed and validated by integrating clinical and imaging variables. Multivariate logistic regression analysis was used to establish the MVI prediction model; three models were developed: a clinical model, a SNZ-CEUS model, and a combined model and conduct external validation. We conducted subgroup analysis to investigate the performance of the SNZ-CEUS model in non-invasive prediction of MVI. RESULTS: Overall, 211 patients were evaluated. All patients were split into derivation (n = 170) and external validation (n = 41) cohorts. Patients who had MVI accounted for 89 of 211 (42.2%) patients. Multivariate analysis revealed that tumor size (> 49.2 mm), pathology differentiation, arterial phase heterogeneous enhancement pattern, non-single nodular gross morphology, washout time (< 90 s), and gray value ratio (≤ 0.50) were significantly associated with MVI. Combining these factors, the area under the receiver operating characteristic (AUROC) of the combined model in the derivation and external validation cohorts was 0.859 (95% confidence interval (CI): 0.803-0.914) and 0.812 (95% CI: 0.691-0.915), respectively. In subgroup analysis, the AUROC of the SNZ-CEUS model in diameter ≤ 30 mm and ˃ 30 mm cohorts were 0.819 (95% CI: 0.698-0.941) and 0.747 (95% CI: 0.670-0.824). CONCLUSIONS: Our model predicted the risk of MVI in HCC patients with high accuracy preoperatively. CLINICAL RELEVANCE STATEMENT: Sonazoid, a novel second-generation ultrasound contrast agent, can accumulate in the endothelial network and form a unique Kupffer phase in liver imaging. The preoperative non-invasive prediction model based on Sonazoid for MVI is helpful for clinicians to make individualized treatment decisions. KEY POINTS: • This is the first prospective multicenter study to analyze the possibility of SNZ-CEUS preoperatively predicting MVI. • The model established by combining SNZ-CEUS image features and clinical features has high predictive performance in both derivation cohort and external validation cohort. • The findings can help clinicians predict MVI in HCC patients before surgery and provide a basis for optimizing surgical management and monitoring strategies for HCC patients.

Microwave ablation vs. surgery for papillary thyroid carcinoma with minimal sonographic extrathyroid extension: a multicentre prospective study.

OBJECTIVES: Minimal extrathyroid extension (mETE) was removed from the TNM staging system. This study was designed prospectively to compare the safety and efficacy of microwave ablation (MWA) versus surgery for treating T1N0M0 papillary thyroid carcinomas (PTC) with sonographically detected mETE. METHODS: From December 2019 to April 2021, 198 patients with T1N0M0 mETE-PTCs evaluated by preoperative ultrasound from 10 hospitals were included. Ninety-two patients elected MWA, and 106 patients elected surgery for treatment. MWA was performed using extensive ablation with hydrodissection. Surgery consisted of lobectomy with ipsilateral central lymph node dissection (CLD), lobe and isthmus excision with ipsilateral CLD and total thyroidectomy with ipsilateral CLD. The rates of technical success, cost, oncologic outcomes, complications and quality of life of the two groups were assessed. RESULTS: The follow-up times for the MWA and surgery groups were 12.7 ± 4.1 and 12.6 ± 5.0 months, respectively. The technical success rate was 100% for both groups. Oncological outcomes of the two groups were similar during the follow-up (all p > 0.05). The MWA group had a shorter operation time, less blood loss and lower costs (all p < 0.001). Three complications (3.3%) were reported in the MWA group and 4 (3.8%) in the surgery group (p = 0.846). The surgery group had higher scores for scar problems and anxiety (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: Microwave ablation was comparable in the short term to surgery in terms of treatment safety and efficacy in selected patients with T1N0M0 mETE-PTC detected by ultrasound. KEY POINTS: • Microwave ablation is comparable to surgery in the safety and short-term efficacy for PTCs with sonographically detected mETE. • Thermal ablation is technically feasible for mETE-PTC treatment. • Patients with mETE-PTC have similar quality of life in the two groups, except for worse scar problems and anxiety in the surgery group.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

BACKGROUND: Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry. METHODS: Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency. RESULTS: The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites). CONCLUSIONS: The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

Intratumoral perfusion may affect microwave ablation area of hepatocellular carcinoma.

OBJECTIVES: We aimed to evaluate the effect of intratumoral perfusion on microwave ablation (MWA) area in hepatocellular carcinoma (HCC). METHODS: Patients who underwent curative MWA for HCC between October 2013 and May 2015 were enrolled. Three days before MWA, contrast-enhanced ultrasound (CEUS) was performed to illustrate the perfusion characteristics of the target lesion. Using the Sonoliver quantification software, time-intensity curves of dynamic CEUS were obtained, and quantitative parameters were extracted. Two microwave antennae were inserted into the center of the tumor and MWA was performed with a continuous power output of 50 W for 5 min. A second CEUS was performed to measure the size of the ablated region. Thereafter, an additional MWA procedure was performed until complete ablation with a 5-10-mm safety margin was achieved. RESULTS: A total of 38 patients who underwent curative MWA for 39 HCC nodules were enrolled. The mean age was 57 years (34-80 years), and the median maximum diameter of the HCC was 3.4 cm (interquartile range, 2-6.8 cm). Time-intensity curves were obtained and the area under the curve (AUC) was selected as a parameter for intratumoral perfusion. The AUC was inversely and linearly correlated with the size of the MWA area, including long- and short-axis diameters and ablation volume. A 1,000-dB·s change in the AUC produced an average change of 1.17 ± 0.44 mm, 0.725 ± 0.355 mm, and 2.4995 ± 0.6575 cm³ in the long- and short-axis diameters and ablation volume, respectively. CONCLUSIONS: The intratumoral perfusion of HCC was inversely correlated with MWA area size.

Microwave ablation without subsequent lumpectomy versus breast-conserving surgery for early breast cancer: a propensity score matching study.

PURPOSE: To compare the efficacy of ultrasound-guided percutaneous microwave ablation (MWA) without subsequent lumpectomy and breast-conserving surgery (BCS) in patients with early breast cancer (BC). MATERIALS AND METHODS: This retrospective cohort study enrolled 106 patients with early BC (T0/1/2 N0/1 M0) treated by MWA (n = 21) or BCS (n = 85) from October 2014 to December 2020. Propensity score matching (PSM) was performed to balance the baseline characteristics between MWA and BCS groups. The tumor progression, overall survival (OS), disease-specific survival (DSS), complications, and cosmetic results were compared. RESULTS: After PSM, there were 21 patients with balanced baseline characteristics in each group. After a median follow-up of 43 months (range, 15-89 months), there was no significant difference in tumor progression (10% vs 2%, p = 0.18), OS (96% vs 99%, p = 0.36), DSS (100% vs 99%, p > 0.99), and complications (0% vs 19%, p = 0.58). The operation time of MWA was shorter (60 min vs 101 min, p < 0.001) than that of BCS. For the management of metastatic lymph nodes, five (5/21, 24%) patients with six metastatic nodes underwent ablation in the MWA group and three patients (3/21, 14%) with six metastatic nodes underwent axillary lymph node dissection in the BCS group. All the patients in the MWA group reported excellent cosmetic results, but 29% of BCS patients expressed dissatisfaction with breast asymmetry (10%) and scar formation (19%) (p < 0.001). CONCLUSION: This pilot study indicated that in selected early BC patients, microwave ablation without subsequent lumpectomy had comparable tumor control effect with breast-conserving surgery and better cosmetic results at an intermediate follow-up.HighlightsMWA without subsequent lumpectomy has a comparable interim survival effect and better cosmetic results as BCS in the treatment of selected early breast cancer.MWA has the potential to be a viable and promising therapeutic option for breast cancer patients reluctant or intolerant to surgery with the advantage of minimal invasion.

Long-term efficacy and safety of microwave ablation for hepatocellular carcinoma adjacent to the gallbladder with a diameter ≤ 5 cm: a multicenter, propensity score matching study.

OBJECTIVE: To compare the long-term efficacy and safety of microwave ablation (MWA) as first-line therapy for hepatocellular carcinoma (HCC) adjacent versus nonadjacent to the gallbladder. MATERIALS AND METHODS: From 2006 to 2018, 657 patients with ≤5 cm HCC who underwent percutaneous ultrasound-guided MWA as first-line therapy from 5 hospitals were enrolled in this retrospective study. Patients were grouped into the adjacent group (n = 49) and the nonadjacent group (n = 608) according to whether the tumor was adjacent to the gallbladder. Propensity score matching (PSM) was used to balance baseline variables between the two groups. RESULTS: Forty-eight patient pairs were matched after PSM. For the PSM cohort, during a median follow-up time of 60 months, there were no differences in PFS (hazard ratio [HR], 1.011; 95% confidence interval [CI], 0.647-1.578; p = 0.963) or OS (HR 0.925; 95% CI 0.522-1.639; p = 0.789) between the adjacent and nonadjacent groups. Univariate and multivariate analyses revealed that the tumor adjacent to the gallbladder was not an independent risk factor for PFS or OS (all p > 0.05). Subgroup analysis showed comparable PFS and OS between the two groups in the <3 cm subgroup and the 3-5 cm subgroups (all p > 0.05). In addition to more use of assistive technology (p < 0.05), the adjacent group shared comparable local tumor progression, complications, technical success rate, and hospital stay (all p > 0.05) to the nonadjacent group. CONCLUSION: There were comparable long-term efficacy and complications between patients with HCC adjacent and nonadjacent to the gallbladder treated with MWA.

The application of MWA to HCC adjacent and nonadjacent to the gallbladder resulted in comparable PFS and OS and complications.For both cohorts, MWA shared comparable complications (immediate and delayed), LTP, hospitalization, and operative time.MWA might be a first-line alternative for ≤5 cm HCC adjacent to the gallbladder with the use of assistive technologies and advances in technology.

On-Site Diagnostic Ability of CEUS/CT/MRI for Hepatocellular Carcinoma (2019-2022): A Multicenter Study.

OBJECTIVES: To compare the on-site diagnostic performance of contrast-enhanced ultrasound (CEUS), computed tomography (CECT), and magnetic resonance imaging (CEMRI) for hepatocellular carcinoma (HCC) across diverse practice settings. METHODS: Between May 2019 and April 2022, a total of 2085 patients with 2320 pathologically confirmed focal liver lesions (FLLs) were enrolled. Imaging reports were compared with results from pathology analysis. Diagnostic performance was analyzed in defined size, high-risk factors for HCC, and hospital volume categories. RESULTS: Three images achieved similar diagnostic performance in classifying HCC from 16 types of FLLs, including HCC ≤2.0 cm. For HCC diagnosis at low-volume hospitals and HCC with high-risk factors, the accuracy and specificity of CEUS were comparable to CECT and CEMRI, while the sensitivity of CEUS (77.4 and 89.5%, respectively) was inferior to CEMRI (87.0 and 92.8%, respectively). The diagnostic accuracy of CEUS + CEMRI and CEUS + CECT increased by 7.8 and 6.2% for HCC ≤2.0 cm, 8.0 and 5.0% for HCC with high-risk factors, and 7.4 and 5.5% for HCC at low-volume hospitals, respectively, compared with CEMRI/CECT alone. CONCLUSIONS: Compared with CECT and CEMRI, CEUS provides adequate diagnostic performance in clinical first-line applications at high-volume hospitals. Moreover, a higher diagnostic performance for HCC is achieved by combining CEUS with CECT/CEMRI compared with any single imaging technique.

The potential mechanism of Choulingdan mixture in improving acute lung injury based on HPLC-Q-TOF-MS, network pharmacology and in vivo experiments.

Choulingdan mixture (CLDM) is an empirical clinical prescription for the adjuvant treatment of acute lung injury (ALI). CLDM has been used for almost 30 years in the clinic. However, its mechanism for improving ALI still needs to be investigated. In this study, high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) was applied to characterize the overall chemical composition of CLDM. A total of 93 ingredients were characterized, including 25 flavonoids, 20 organic acids, 11 saponins, nine terpenoids, seven tannins and 21 other compounds. Then network pharmacology was applied to predict the potential bioactive components, target genes and signaling pathways of CLDM in improving ALI. Additionally, molecular docking was performed to demonstrate the interaction between the active ingredients and the disease targets. Finally, animal experiments further confirmed that CLDM significantly inhibits pulmonary inflammation, pulmonary edema and oxidative stress in lipopolysaccharide-induced ALI mice by inhibiting the PI3K-AKT signaling pathway. This study enhanced the amount and accuracy of compounds of CLDM and provided new insights into CLDM preventing and treating ALI.