Corrigendum: Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: from static images to CEUS video analysis.

[This corrects the article DOI: 10.3389/fonc.2022.951973.].

Multimodal ultrasound features of breast cancers: correlation with molecular subtypes.

OBJECTIVES: To investigate whether multimodal intratumour and peritumour ultrasound features correlate with specific breast cancer molecular subtypes. METHODS: From March to November 2021, a total of 85 patients with histologically proven breast cancer underwent B-mode, real-time elastography (RTE), colour Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The time intensity curve (TIC) of CEUS was obtained, and the peak and time to peak (TTP) were analysed. Chi-square and binary logistic regression were used to analyse the connection between multimodal ultrasound imaging features and breast cancer molecular subtype. RESULTS: Among 85 breast cancers, the subtypes were as follows: luminal A (36 cases, 42.4%), luminal B (20 cases, 23.5%), human epidermal growth factor receptor-2 positive (HER2+) (16 cases, 18.8%), and triple negative breast cancer (TNBC) (13 cases, 15.3%). Binary logistic regression models showed that RTE (P < 0.001) and CDFI (P = 0.036) were associated with the luminal A cancer subtype (C-index: 0.741), RTE (P = 0.016) and the peak ratio between intratumour and corpus mamma (P = 0.036) were related to the luminal B cancer subtype (C-index: 0.788). The peak ratio between peritumour and intratumour (P = 0.039) was related to the HER2 + cancer subtype (C-index: 0.859), and CDFI (P = 0.002) was associated with the TNBC subtype (C-index: 0.847). CONCLUSIONS: Multimodal ultrasound features could be powerful predictors of specific breast cancer molecular subtypes. The intra- and peritumour CEUS features play assignable roles in separating luminal B and HER2 + breast cancer subtypes.

Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: From static images to CEUS video analysis.

Background: Continuous contrast-enhanced ultrasound (CEUS) video is a challenging direction for radiomics research. We aimed to evaluate machine learning (ML) approaches with radiomics combined with the XGBoost model and a convolutional neural network (CNN) for discriminating between benign and malignant lesions in CEUS videos with a duration of more than 1 min. Methods: We gathered breast CEUS videos of 109 benign and 81 malignant tumors from two centers. Radiomics combined with the XGBoost model and a CNN was used to classify the breast lesions on the CEUS videos. The lesions were manually segmented by one radiologist. Radiomics combined with the XGBoost model was conducted with a variety of data sampling methods. The CNN used pretrained 3D residual network (ResNet) models with 18, 34, 50, and 101 layers. The machine interpretations were compared with prospective interpretations by two radiologists. Breast biopsies or pathological examinations were used as the reference standard. Areas under the receiver operating curves (AUCs) were used to compare the diagnostic performance of the models. Results: The CNN model achieved the best AUC of 0.84 on the test cohort with the 3D-ResNet-50 model. The radiomics model obtained AUCs between 0.65 and 0.75. Radiologists 1 and 2 had AUCs of 0.75 and 0.70, respectively. Conclusions: The 3D-ResNet-50 model was superior to the radiomics combined with the XGBoost model in classifying enhanced lesions as benign or malignant on CEUS videos. The CNN model was superior to the radiologists, and the radiomics model performance was close to the performance of the radiologists.

A Novel Biopsy Method Based on Bipolar Radiofrequency Biopsy Needles.

Modern oncology increasingly relies on pathological, molecular, and genomic assessments of biopsied tumor tissue. However, the concern for bleeding complication and malignant seeding severely hinders the application of the biopsy tumor. Here, we developed a 16 G biopsy needle to contain two electrodes insulated from each other and connect to an radiofrequency generator. For evaluating hemostatic efficacy, 50 rabbits were randomly divided into two groups: warfarinization and non-warfarinization group. Two liver biopsies and two splenic biopsies per animal were performed using a 16 G biopsy needle. Each group was further equally divided into five groups according to different hemostatic measures, including non-intervention, embolization using an absorbable gelatin sponge, and ablation by RF with three different needle temperatures (50°C, 70°C, and 90°C). Than, we used VX2 rabbit models (n = 25) and applied the five analogous biopsies to the tumor. The flush fluid from the biopsy needle underwent cytomorphological analysis. Our results that the groups using ablation by RF showed significantly less blood loss than the control group for liver and spleen in both groups (P < 0.001). After RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed on both the macroscopic and histological level. Cytological smears showed that tumor cells were degenerated after RF at 70°C and 90°C. Our findings showed that bipolar RF biopsy needle is a promising tool for reducing hemorrhage after biopsy and avoiding implanting tumor cells in the tract.

Combination therapy with low-frequency ultrasound irradiation and radiofrequency ablation as a synergistic treatment for pancreatic cancer.

We aim to evaluate the efficacies of combination therapy with low-frequency ultrasound-stimulated microbubbles (USMB) and radiofrequency ablation (RFA) on suppressing the proliferation of pancreatic cancer cell and treating Panc02 subcutaneous xenograft mice. The proliferation of HPDE6-C7 and Panc02 cells after the treatment of USMB and RFA alone or combination were evaluated by CCK-8 assay. Scratch test was performed to assess the cell migration capability. Panc02-bearing mice were received 14-day treatment of USMB and RFA alone or combination. Tumor size and survival rate were recorded once two days. The serum levels of immune-related factors and changes of apoptosis- and autophagy-related factors were detected by ELISA and western blotting methods. As a result, CKK-8 assays revealed significant inhibition on Panc02 cell proliferation in combination therapy with USMB and RFA relative to other groups (all p < 0.05). Strong synergistic effect of USMB combined with RFA was confirmed via the calculated combination index (CI) <0.4. In addition, combination therapy of USMB and RFA significantly inhibited the migration of Panc02 cells. Moreover, combined treatment remarkably inhibited the size and width of xenograft and improved the survival in Panc02-bearing mice. Furthermore, 14-day combination therapy of USMB and RFA in Panc02-bearing mice significantly facilitated the apoptosis and autophagy of tumor cells. In summary, combination therapy of USMB and RFA showed synergistic anti-tumor efficacies on Panc02 cells attributing to the promotion on apoptosis and autophagy in Panc02 subcutaneous xenograft mice.

CEUS-Based Radiomics Can Show Changes in Protein Levels in Liver Metastases After Incomplete Thermal Ablation.

OBJECTIVE: To investigate the ability of contrast-enhanced ultrasound (CEUS)-based radiomics combined with machine learning to detect early protein changes after incomplete thermal ablation. METHODS: HCT-26 colorectal adenoma cells were engrafted into the livers of 80 mice, which were randomly divided into 4 groups for palliative laser ablation. Changes in heat shock protein (HSP) and apoptosis-related protein expression in the tumors were assessed. SCID mice subjected to CEUS and ultrasonography were divided into training (n=56) and test (n=24) datasets. Then, 102 features from seven feature groups were extracted. We use the least absolute shrinkage and selection operator (LASSO) feature selection method to fit the machine learning classifiers. The feature selection methods and four classifiers were combined to determine the best prediction model. RESULTS: The areas under the receiver-operating characteristic curves (AUCs) of the classifiers in the test dataset ranged from 0.450 to 0.932 (median: 0.721). The best score was obtained from the model in which the omics data of CEUS was analyzed in the arterial phase by random forest (RF) classification. CONCLUSIONS: A machine learning model, in which radiomics characteristics are extracted by multimodal ultrasonography, can accurately, rapidly and noninvasively identify protein changes after ablation.

Endoscopic ultrasound-guided sampling using core biopsy needle for diagnosis of left-lobe hepatocellular carcinoma in patients with underlying cirrhosis.

OBJECTIVE: The objective is to evaluate the application of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in the diagnosis of the left-lobe hepatocellular carcinoma (HCC) in cirrhotic patients with contraindication to percutaneous biopsy. MATERIALS AND METHODS: Thirty-eight consecutive patients with liver cirrhosis and suspected left-lobe HCC and with contraindication for percutaneous biopsy undergoing EUS-FNB between January 2011 and December 2014 were included in this study. The final diagnosis was obtained through histopathology of surgical samples or clinical and imaging results with follow-up. Using the final diagnosis as the gold standard, the diagnostic performance of EUS-FNB for HCC detection was evaluated. RESULTS: Among 38 patients, EUS-FNB was successfully performed in 34 cases, in which adequate biopsy specimens were obtained for histopathological examination in 30. For the 30 patients with biopsy results, 25 cases were confirmed to have HCC, while five cases had benign lesions according to the final diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rates of EUS-FNB in the diagnosis of HCC were 88.0% (22/25), 100.0% (5/5), 100.0% (22/22), 62.5% (5/8), and 90.0% (27/30), respectively. Self-limiting bleeding occurred in three patients. CONCLUSIONS: EUS-FNB is a sensitive and safe diagnostic modality for cirrhotic patients with suspected HCC located in the left lobe, especially those for whom percutaneous biopsy is contraindicated.

Combination of HSP90 and autophagy inhibitors promotes hepatocellular carcinoma apoptosis following incomplete thermal ablation.

The present study evaluated the effect of combining inhibitors (17­AAG) of heat shock protein 90 (HSP90) and autophagy (3­MA) on apoptosis using an incomplete thermal ablation animal model. A total of 28 orthotopic mice with hepatocellular carcinoma were randomly divided into 4 groups to receive different drug interventions. Following palliative laser ablation, changes in autophagy, apoptosis and Akt/mTOR expression levels were assessed in tumors. Compared with the controls, the 17­AAG­treated mice exhibited significantly decreased expression levels of phosphorylated (p)­Akt and p­mTOR with enhanced autophagy and apoptosis; no marked increases in the expression levels of p­Akt and p­mTOR were observed in the 3­MA­treated mice, with no significant changes in autophagy; however, apoptosis was enhanced. No significant decreases in p­Akt and p­mTOR or any increase in autophagy were observed in the mice receiving a combination of 17­AAG and 3­MA, but they did exhibit a marked increase in apoptosis. Compared with 17­AAG alone, the combination of 17­AAG and 3­MA resulted in a marked increase in apoptosis without enhanced autophagy. In the incomplete ablation model, the effects of autophagy and apoptosis are antagonistic. The combined use of 17­AAG and 3­MA can significantly promote apoptosis and is worthy of further study.

Heat shock protein expression and autophagy after incomplete thermal ablation and their correlation.

OBJECTIVE: To establish a model of incomplete ablation in nude mice with hepatocellular carcinoma (HCC) and to evaluate heat shock protein (HSP) expression and autophagy and their correlation. MATERIALS AND METHODS: In the first stage, 12 nude mice with HCC were randomly divided into two groups (n = 6). A sham puncture operation was performed for one group, and palliative laser ablation was performed for the other group. All mice were sacrificed after 18 h, and HSP expression, autophagy, and apoptosis were assessed. In the second stage, 16 nude mice with HCC were randomly divided into two groups (n = 8). One group was given an HSP90 inhibitor before the operation, and the other group was given dimethyl sulfoxide (DMSO) as a control. HSP expression, autophagy and apoptosis were assessed for the two groups after palliative laser ablation. RESULTS: In the incomplete ablation model, using nude mice with HCC, HSP90, HSP70, and HSP27 expression was up-regulated, Akt and mTOR phosphorylation was enhanced, autophagy was decreased, and apoptosis was increased. After administration of the HSP90 inhibitor, HSP90, P-Akt, and P-mTOR expression was decreased, autophagy was increased, and apoptosis was further increased. CONCLUSION: Autophagy was decreased in the incomplete ablation model and might be inversely correlated with HSP expression. It is suggested that the HSP90/Akt/mTOR pathway is involved in signal transmission between autophagy and HSPs.

Systematic Review and Meta-Analysis of Diagnostic Accuracy of Endoscopic Ultrasound (EUS)-Guided Fine-Needle Aspiration (FNA) Using 22-gauge and 25-gauge Needles for Pancreatic Masses.

BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been used for detecting pancreatic cancer. We aimed to compare the diagnostic yield of both 22-gauge and 25-gauge EUS-FNA for the detection of pancreatic cancer. MATERIAL AND METHODS We searched the electronic databases including PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library up to June 13, 2017. Two reviewers independently screened studies and extracted data. RESULTS We analyzed data from 1824 patients from 16 included studies. The estimated pooled data for the 22-gauge needles reported sensitivity was 0.89 (0.83-0.93), specificity was 1.00 (0.74-1.00), positive LR was 485.28 (2.55-92 000) and negative LR was 0.11 (0.07-0.17). Results for the 25-gauge needles showed the pooled sensitivity, specificity, positive and negative LR was 0.90 (0.86-0.93), 0.99 (0.89-1.00), 59.53 (7.99-443.66), and 0.10 (0.07-0.14), respectively. The 25-gauge needle had significantly higher pooled sensitivity than the 22-gauge needle (0.90 vs. 0.87, χ²=5.26, P=0.02) while there was no difference in the pooled specificity (0.96 vs. 0.98, χ²=2.12, P=0.15). The quality of most studies was assessed favorable using QUADAS-2 (quality assessment of diagnostic accuracy studies-2). CONCLUSIONS Our findings revealed that the 25-gauge EUS-FNA used for pancreatic lesions could have a higher diagnostic yield than using 22-gauge EUS-FNA. Nevertheless, well-designed prospective studies recruiting more patients are needed.

EUS dating with laser ablation against the caudate lobe or left liver tumors: a win-win proposition?

Endoscopic ultrasound (EUS) have been not only a diagnostic tool, but also available in interventional therapy, which often previously needed surgical approaches to achieve. The study aimed to evaluate the effectiveness and safety of EUS-guided Nd:YAG laser ablation in unresectable tumors of the caudate lobe and left liver. We discussed ten cases of the caudate lobe and left liver tumors underwent laser ablation with EUS guidance. And we also have reviewed previous publication of EUS-guided thermal ablation for liver tumors in several decade years. EUS-guided Nd:YAG laser ablation (LA) of these tumors were successfully completed in ten patients, who had favourable prognosis with no complications in two-month follow-up. Based on our early observations, this suggested that EUS-guided LA might be technically feasible in selected patients with tumors of the caudate lobe and left liver. However, the safety of this technique need to be further confirmed in the future and if possible larger, prospective trials.

Percutaneous laser ablation: a new contribution to unresectable high-risk metastatic retroperitoneal lesions?

BACKGROUND & AIMS: Metastasis in retroperitoneal lymph nodes is one of the signs of advanced stage or terminal stage of malignancy. We performed a trial to assess the safety and efficacy of ultrasonography (US)-guided local neodymium-doped yttrium aluminum garnet (Nd:YAG) laser ablation for metastatic lymph nodes in the retroperitoneal region. METHODS: We evaluated 4 cases of retroperitoneal metastatic lymph nodes treated using US-guided Nd:YAG laser ablation. Additionally, we reviewed the PubMed database for articles on thermal ablation of retroperitoneal lesions until March 2016, without language limitations. RESULTS: In our study, all lesions were nearly completely ablated with mild discomfort, including pain and fever at the 3-month follow-up. In the literature review, a total of 398 patients with 491 retroperitoneal tumors were identified, and complications after the procedure included enterovesical fistula, fecal incontinence, and hematoma. CONCLUSIONS: Percutaneous laser ablation could be a theoretically promising approach for retroperitoneal metastatic lesions. ClinicalTrials.gov number: NCT02822053.

Inaccurate preoperative imaging assessment on biliary anatomy not increases biliary complications after living donor liver transplantation.

BACKGROUNDS AND AIMS: Accurate assessment of graft bile duct is important to plan surgical procedure. Magnetic resonance cholangiopancreatography (MRCP) has become an important diagnostic procedure in evaluation of pancreaticobiliary ductal abnormalities and has been reported as highly accurate. We aim to estimate the efficacy of preoperative MRCP on depicting biliary anatomy in living donor liver transplantation (LDLT), and to determine whether inaccurate preoperative imaging assessment would increase the biliary complications after LDLT. METHODS: The data of 118 cases LDLT were recorded. Information from preoperative MRCP was assessed using intraoperative cholangiography (IOC) as the gold standard. The possible risk factors of recipient biliary complications were analyzed. RESULTS: Of 118 donors, 84 had normal anatomy (type A) and 34 had anatomic variants (19 cases of type B, 9 cases of type C, 1 case of type E, 2 cases of type F and 3 cases of type I) confirmed by IOC. MRCP correctly predicted all 84 normal cases and 17 of 34 variant cases, and showed an accuracy of 85.6% (101/118). The incidence of biliary complications was comparable between cases with accurate and inaccurate classification of biliary tree from MRCP, and between cases with normal and variant anatomy of bile duct. While cases with graft duct opening ≤5mm showed a significant higher incidence of total biliary complications (21.1% vs. 6.6%, P=0.028) and biliary stricture (10.5% vs. 1.6%, P=0.041) compared with cases with large duct opening >5mm. CONCLUSION: MRCP could correctly predict normal but not variant biliary anatomy. Inaccurate assessment of biliary anatomy from MRCP not increases the rate of biliary complications, while small-sized graft duct may cause an increase in biliary complications particularly biliary stricture after LDLT.

Emergency embolization in the treatment of ruptured hepatocellular carcinoma following transcatheter arterial chemoembolization.

BACKGROUND/AIMS: Rupture of hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE) is a rare and life-threatening complication. The purpose of the present study was to evaluate the utility of emergency embolization for treatment of ruptured HCC following TACE. METHODOLOGY: Five patients developed rupture of tumor after TACE in 1005 patients of HCC from October 2007 to February 2010, and were studied retrospectively. Emergency selective arterial embolization was performed in all 5 patients because of intractable hemorrhage in the peritoneal cavity or around the liver that could not be controlled by conservative method. The mean hemoglobin level before embolization was 75.6 g/L +/- 20.7 (mean +/- standard deviation). RESULTS: Hepatic angiography did not revealed extravasation of contrast from the tumor in all 5 patients with rupture of HCC following TACE. After selective embolization of feeding arteries of the liver tumor, intraperitoneal bleeding from HCC was stopped immediately in all patients. The mean hemoglobin level after embolization in 48 hours was 102.6 g/L +/- 3.5. No severe complication related to emergency embolization was found after treatment. CONCLUSIONS: Emergency arterial embolization is effective for hemostasis of ruptured HCC following TACE in patients with hemodynamically unstable condition.