Dendritic cell-cytokine killer combined with microwave ablation reduced recurrence for hepatocellular carcinoma compared to ablation alone.

BACKGROUND: Several international practice guidelines have recommended local ablation as the first-line treatment for early-stage hepatocellular carcinoma (HCC). OBJECTIVE: This study aims to investigate the synergetic anti-tumor impact of dendritic cell-cytokine killer (DC-CIK) combined with microwave ablation (MWA) for HCC. METHODS: This retrospective study included 1,141 patients from the American Joint Committee on Cancer stage I-II HCC, who were treated with therapeutic MWA. The immunotherapy group encompassing 40 patients received additional immunotherapy with DC-CIK, whereas the control group consisting of 1,101 patients was treated with MWA alone. Propensity score matching (PSM) with ratio of 1:3 was employed to balance selection bias. The oncological outcome and immune status were measured after combination therapy. RESULTS: The immunotherapy group patients exhibited significant longer disease-free survival (DFS, primary HCC: p= 0.036; recurrent HCC: p= 0.026). For patients with primary HCC, the recurrence frequency was reduced (p= 0.002), and recurrence interval (19 months vs. 9 months, p< 0.001) was prolonged in the immunotherapy group. Subgroup analysis revealed that patients ⩽ 60 years old, moderately-differentiated HCC, or co-infected with Hepatitis B Virus (HBV) had a significant benefit over DFS in the immunotherapy group. After combination therapy, the serum CD3+ (p= 0.049), CD8/CD28+ (p= 0.045) were elevated. CONCLUSION: Combination therapy with DC-CIK and MWA can significantly reduce the recurrence and prolong DFS, especially for patients ⩽ 60 years old or with moderately-differentiated HCC or co-infected with HBV.

Radiomics Based on Contrast-Enhanced Ultrasound Images for Diagnosis of Pancreatic Serous Cystadenoma.

OBJECTIVE: The purpose of the study was to develop and validate a radiomics model by using contrast-enhanced ultrasound (CEUS) data for pre-operative differential diagnosis of pancreatic cystic neoplasms (PCNs), especially pancreatic serous cystadenoma (SCA). METHODS: Patients with pathologically confirmed PCNs who underwent CEUS examination at Chinese PLA hospital from May 2015 to August 2022 were retrospectively collected. Radiomic features were extracted from the regions of interest, which were obtained based on CEUS images. A support vector machine algorithm was used to construct a radiomics model. Moreover, based on the CEUS image features, the CEUS and the combined models were constructed using logistic regression. The performance and clinical utility of the optimal model were evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity and decision curve analysis. RESULTS: A total of 113 patients were randomly split into the training (n = 79) and test cohorts (n = 34). These patients were pathologically diagnosed with SCA, mucinous cystadenoma, intraductal papillary mucinous neoplasm and solid-pseudopapillary tumor. The radiomics model achieved an AUC of 0.875 and 0.862 in the training and test cohorts, respectively. The sensitivity and specificity of the radiomics model were 81.5% and 86.5% in the training cohort and 81.8% and 91.3% in the test cohort, respectively, which were higher than or comparable with that of the CEUS model and the combined model. CONCLUSION: The radiomics model based on CEUS images had a favorable differential diagnostic performance in distinguishing SCA from other PCNs, which may be beneficial for the exploration of personalized management strategies.

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.

Peripheral immune factors aiding clinical parameter for better early recurrence prediction of hepatocellular carcinoma after thermal ablation.

OBJECTIVES: Current predictors are largely unsatisfied for early recurrence (ER) of hepatocellular carcinoma (HCC) after thermal ablation. We aimed to explore the prognostic value of peripheral immune factors (PIFs) for better ER prediction of HCC after thermal ablation. METHODS: Patients who received peripheral blood mononuclear cells (PBMCs) tests before thermal ablation were included. Clinical parameters and 18 PIFs were selected to construct ModelClin, ModelPIFs and the hybrid ModelPIFs-Clin. Model performances were evaluated using area under the curve (AUC), and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis and log-rank tests. RESULTS: 244 patients were included and were randomly divided in 3:1 ratio to discovery and validation cohorts. Clinical parameters including tumor size and AFP, and PIFs including neutrophils, platelets, CD3+CD16+CD56+ NKT and CD8+CD28- T lymphocytes were selected. The ModelPIFs-Clin showed increase in predictive performance compared with ModelClin, with the AUC improved from 0.664 (95%CI:0.588-0.740) to 0.801 (95%CI:0.734-0.867) in discovery cohort (p < 0.0001), and from 0.645 (95%CI:0.510-0.781) to 0.737(95%CI:0.608-0.865) in validation cohort (p = 0.1006). ModelPIFs-Clin enabled ER risk stratification of patients. Patients predicted in ModelPIFs-Clin high-risk subgroup had a poor RFS compared with those predicted as ModelPIFs-Clin low-risk subgroup, with the median RFS was 18.00 month versus 100.78 month in discovery cohort (p < 0.0001); and 24.00 month versus 60.35 month in validation cohort (p = 0.288). Patients in different risk subgroups exhibited distinct peripheral immune contexture. CONCLUSIONS: Peripheral immune cells aiding clinical parameters boosted the prediction ability for ER of HCC after thermal ablation, which be helpful for pre-ablation ER risk stratification.

Huaier granule prevents the recurrence of early-stage hepatocellular carcinoma after thermal ablation: A cohort study.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinical trials have demonstrated that Trametes robinophila Murr (Huaier granule) can inhibit recurrence and metastasis after hepatocellular carcinoma (HCC) resection, but its efficacy as an adjuvant therapy after thermal ablation of early HCC is unknown. AIM OF THE STUDY: To analyze the prognostic value and side effects of Huaier granules in HCC patients undergoing thermal ablation. MATERIALS AND METHODS: Clinical information from 340 eligible subjects with early-stage HCC who were admitted to our department from September 1, 2008 to January 1, 2019 was extracted from the electronic medical record database. They were divided into the thermal ablation + TCM group and the thermal ablation group. Differences in their overall survival (OS), progression-free survival (PFS), extrahepatic metastatic rate (EMR), and therapeutic side effects (TSEs) between the two groups were compared. Beneficiaries of the integrated treatment and adequate treatment length were predicted. RESULTS: The median follow-up was 32.5 months (range 2-122 months). The 1-year, 3-year and 5-year OS rates in the integrated treatment group and the control group were 93.2% vs. 92.6%, 54.5% vs. 51.4%, 23.5% vs. 19.7% (p = 0.110, HR 0.76(0.54-1.07)). The 1-year, 3-year and 5-year PFS rates were 78.8% vs. 69.4%, 50.6% vs. 40.6%, 35.3% vs. 26.5%, respectively (p = 0.020, HR 0.67(0.48-0.94)). The median OS (35 vs. 31 months) and PFS (24 vs. 12.5 months) were longer in the integrated treatment group. The EMR in the integrated treatment group was significantly lower than that in the control group (p = 0.018, HR 0.49 (0.27-0.89)). Patients with any two of the following three factors might be predicted to be beneficiaries of the integrated treatment, including younger than 65 years (p =0.039, HR 0.70 (0.50-0.98)), single tumor (p = 0.035, HR 0.70 (0.50-0.98), and tumor size ≤3 cm (p = 0.029, HR 0.69 (0.50-0.96). Patients with continuous oral administration of TCM following ablation had a lower probability of recurrence and metastasis within 2 years (p = 0.015, HR 0.67 (0.49-0.93)). Although the integrated treatment group reported a higher incidence of nausea and emesis, there were no significant differences between the two groups. CONCLUSION: TCM following ablation may prolong PFS and suppress recurrence in patients with HCC, with continuous oral administration for more than 2 years maybe experience a greater benefit. The TSEs of the treatment are mild and can be tolerated.

Voting Data-Driven Regression Learning for Accelerating Discovery of Advanced Functional Materials and Applications to Two-Dimensional Ferroelectric Materials.

Regression machine learning is widely applied to predict various materials. However, insufficient materials data usually leads to poor performance. Here, we develop a new voting data-driven method that could generally improve the performance of the regression learning model for accurately predicting properties of materials. We apply it to investigate a large family (2135) of two-dimensional hexagonal binary compounds focusing on ferroelectric properties and find that the performance of the model for electric polarization is indeed greatly improved, where 38 stable ferroelectrics with out-of-plane polarization including 31 metals and 7 semiconductors are screened out. By unsupervised learning, actionable information such as how the number and orbital radius of valence electrons, ionic polarizability, and electronegativity of constituent atoms affect polarization was extracted. Our voting data-driven method not only reduces the size of materials data for constructing a reliable learning model but also enables one to make precise predictions for targeted functional materials.

Complications of ultrasound-guided percutaneous microwave ablation of renal cell carcinoma.

PURPOSE: To retrospectively review the complications of ultrasound (US)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma. PATIENTS AND METHODS: In this study, 101 patients with 105 tumors seen from April 2006 to Feb 2014 were enrolled retrospectively. The patients were treated with US-guided percutaneous MWA and were followed up with contrast-enhanced US and computed tomography or magnetic resonance imaging at 1, 3, and 6 months and every 6 months thereafter. RESULTS: Technical success was achieved in 99 of 105 tumors (94.3%). The median follow-up time was 25 (range 1.13-93.23) months. Among the 105 tumors, 26 complications in 24.8% of patients and 23 minor complications (Clavien-Dindo Grades I and II) in 21.9% of patients were noted, accounting for 88.5% of all complications. All the minor complications were cured. Three major complications (Clavien-Dindo Grade ≥III) occurred in 2.9% of the patients, accounting for 11.5% of all complications: hydrothorax in two patients and bowel injury in one. The two patients who had hydrothorax post-MWA had a history of cirrhosis and were treated with catheter drainage. The bowel injury was treated surgically. In all patients, the changes in serum creatinine and urea nitrogen levels from before to after the procedure were small. CONCLUSION: US-guided percutaneous MWA is a beneficial treatment for renal cell carcinoma in selected patients; however, if the renal tumor is close to the bowel, or the patient has serious comorbidities or has undergone abdominal surgery, the procedure must be performed more carefully.

Variables associated with vaginal discharge after ultrasound-guided percutaneous microwave ablation for adenomyosis.

Objective The aim of this study was to analyse the significant variables for vaginal discharge after ultrasound-guided percutaneous microwave ablation (PMWA) therapy. Materials and methods PMWA was performed on 117 patients with adenomyosis from October 2012 to July 2014. The presence or absence, colour, quantity and duration of vaginal discharge, which was different from pre-ablation, were recorded within 1 year after PMWA. Patients were categorised into G1 (n = 26, without vaginal discharge), G2 (n = 40, vaginal discharge lasting 1 to 19 days), and G3 (n = 51, vaginal discharge lasting ≥20 days) groups. The potentially correlative variables were analysed. Variables with significant correlations with vaginal discharge post-ablation were identified via binary logistic regression analysis. Results The differences in adenomyosis type, pre-ablation uterine volume, total microwave ablation energy, total non-perfused volume (NPV) and minimum distance from the non-perfused lesion (NPL) margin to the endomyometrial junction (EMJ) among groups were statistically significant (p = 0.005, p = 0.000, p = 0.000, p = 0.005 and p = 0.000, respectively). Minimum distance from the NPL margin to the EMJ was the strongest predictor of vaginal discharge post-ablation with odds ratio (OR) 0.632, p = 0.018, 95% CI 0.432-0.923. Patients with diffuse adenomyosis were more likely to have prolonged vaginal discharge (≥20 days) post-ablation (OR 3.461, p = 0.000, 95% CI 1.759-7.536). Conclusion The minimum distance from the NPL margin to the EMJ and adenomyosis type were significantly associated with vaginal discharge post-ablation.

Multiple courses of immunotherapy with different immune cell types for patients with hepatocellular carcinoma after microwave ablation.

The aim of the present study was to investigate the therapeutic efficacy of immunotherapy after microwave ablation (MWA), which was used to improve liver function, reduce the recurrence rate and enhance survival period in patients with hepatocellular carcinoma (HCC). Between February 2009 and December 2010, 14 patients received immunotherapy after MWA (immunotherapy group) and 15 patients received MWA alone with no post-ablated adjuvant therapy (control group). Immune and liver parameters, recurrence rate and survival time were recorded. The absolute lymphocyte count in the immunotherapy group exceeded that in the control group after 3 courses of immunotherapy (P<0.05). No significant differences were detected in the lymphocyte subset distribution in the control and immunotherapy patients prior to ablation (P>0.05); however, certain cytotoxic subsets (CD3+/CD8+, CD8+CD28+ and CD3+CD16+CD56+ T cells) were over-represented and negative regulatory or helper subsets (CD4+CD8+, CD4+, CD4+CD25+) were under-represented in the immunotherapy group between 1 and 12 months after immunotherapy (P<0.05). After 2 courses of immunotherapy the proliferation rate of myeloid dendritic cells and T lymphocytes, including CD3+/CD8+ lymphocytes, significantly increased (P<0.05 and P<0.01, respectively). In addition, the level of albumin in the immunotherapy group exceeded that in the control group after 3 courses of immunotherapy (P<0.05). However, the rate of disease-free survival and overall survival within 16 months of MWA did not differ significantly between the two groups (P>0.05). In conclusion, the results of the present study indicate that immunotherapy improves the immune status and liver function of patients with HCC.

[Follow-ups of mid-term and long-term outcomes for uterine intramural myomas after percutaneous microwave ablation therapy].

OBJECTIVE: To evaluate the mid-term and long-term clinical outcomes for symptomatic intramural uterine myoma after ultrasound-guided percutaneous microwave ablation therapy (PMAT). METHODS: A total of 123 women with intramural uterine myoma underwent PMAT. Prospective studies were conducted to compare the dominant fibroid volume (FV), hemoglobin (HGB) and Uterine Fibroid Symptoms and Quality of Life Questionnaire (UFS-QOL) at baseline and 1, 2, 3 and 4 years of follow-up RESULTS: Comparing with the baseline, the shrinkage rate of FV at 1 year follow-up was 74.5%. HGB of anemic patients pre-PMAT increased from 91 ± 11 to 114 ± 20 g/L. Two parts of UFS-QOL symptoms severity scores (SSS) and health-related quality of life (HRQL) changed from 43 ± 10 to 18 ± 16 and 41 ± 21 to 90 ± 16 respectively at 1year follow-up. All four items stayed nearly the same at 2, 3 and 4 years post-therapy. CONCLUSION: Ultrasound-guided PMAT of uterine fibroids can effectively ameliorate the mid-term and long-term clinical syndromes and improve quality of life by shrinking fibroids effectively or even disappearing completely.

Ultrasound-guided percutaneous microwave ablation for submucosal uterine fibroids.

STUDY OBJECTIVE: To prospectively evaluate the efficiency and safety of ultrasound-guided percutaneous microwave ablation (PMWA) in treating symptomatic submucosal uterine myomas. DESIGN: Self-controlled study (Canadian Task Force classification II-1). SETTING: Single center. PATIENTS: Twenty-two premenopausal women with 22 symptomatic submucosal uterine myomas. INTERVENTION: All patients underwent ultrasound-guided PMWA. MEASUREMENTS AND MAIN RESULTS: PMWA was performed in 22 premenopausal women with 22 symptomatic submucosal uterine myomas. Mean (SD) patient age was 42 (4.60) years (95% confidence interval [CI], 39.96-44.04). Five symptomatic submucosal uterine myomas were identified as type 0, 7 as type 1, and 10 as type 2. Contrast-enhanced ultrasound and magnetic resonance imaging were performed before and after surgery. Myoma volume, hemoglobin concentration, and scores on the UFS-QOL (Uterine Fibroid Symptom and Quality of Life) questionnaire were recorded before and at 3 and 12 months after ablation. Complications were also recorded. In all patients, therapy was completed with a single ablation. The baseline diameter of the symptomatic submucosal uterine myomas was 4.90 (1.60) cm. Mean myoma volume reduction rate was 81.46% (16.33%) (95% CI, 73.06%-89.86%) at 3 months (p < .001) and reached 90.00% (9.79%) (95% CI, 85.07-95.13) at 12 months (p < .001). At 3 months after ablation, hemoglobin concentration increased from 88.64 (21.87) g/L (95% CI, 78.94-98.34) to 123.21 (15.77) g/L (95% CI, 115.10-131.32) (p < .001), and remained stable at 12 months, with a value of 125.92 (14.90) g/L (95% CI, 117.98-133.86). Scores on the UFS-QOL were comparable, with normal levels observed at 1 year. No major complications were observed. Nine patients were discharged with necrotic masses. CONCLUSION: PMWA seems to be effective and safe for treatment of submucosal myomas.