Evaluation of Contrast-enhanced US LI-RADS version 2017: Application on 2020 Liver Nodules in Patients with Hepatitis B Infection.

Background Use of contrast material-enhanced (CE) US Liver Imaging Reporting and Data System (LI-RADS) version 2017 has not been validated in large populations where hepatitis B virus (HBV) is endemic. Purpose To evaluate the diagnostic performance of CE US LI-RADS version 2017 in a population with a high prevalence of HBV infection. Materials and Methods In this retrospective study, liver nodules in patients with HBV who were evaluated from January 2004 to December 2016 were categorized as CE US LR-1 to LR-5 through LR-M. A subgroup of LR-M nodules was reclassified as LR-5, and additional analysis was performed. The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. Diagnostic performance was assessed with sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Results A total of 2020 nodules in 1826 patients (median age, 54 years ± 12 [standard deviation]; 1642 men) were included. Of the 1159 LR-5 lesions, 1141 were hepatocellular carcinoma (HCC); three, intrahepatic cholangiocarcinomas; six, other malignancies; six, atypical hyperplasia; and three, benign lesions. The PPV of LR-5 for HCC was 98% (95% confidence interval [CI]: 98%, 99%). In LR-M nodules, 153 showed arterial phase hyperenhancement, early washout, and absence of punched-out appearance within 5 minutes, and 142 of 153 (93%; 95% CI: 89%, 97%) were HCC. If these nodules were reclassified as LR-5, LR-M specificity and PPV as a predictor of non-HCC malignancy increased from 88% (95% CI: 87%, 89%) and 36% (95% CI: 31%, 41%) to 96% (95% CI: 95%, 97%) and 58% (95% CI: 51%, 65%), respectively (P < .001). Despite reclassification, LR-5 specificity and PPV remained high (94% [95% CI: 92%, 96%] and 98% [95% CI: 97%, 99%], respectively). Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System version 2017 category LR-5 is effectively predictive of the presence of hepatocellular carcinoma. In patients with hepatitis B virus infection, performance may be further improved by reclassification of category LR-M nodules with arterial phase hyperenhancement, early washout, and no punched-out appearance to LR-5. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sidhu in this issue.

Evaluation of liver parenchyma stiffness in patients with liver tumours: optimal strategy for shear wave elastography.

OBJECTIVES: To determine the methodology of non-invasive test for evaluation of liver stiffness (LS) with tumours using two-dimensional (2D) shear wave elastography (SWE). METHODS: One hundred and twenty-seven patients with liver tumours underwent 2D-SWE before surgery to measure liver and spleen stiffness (SS). Two-dimensional SWE values were obtained in the liver at 0-1 cm, 1-2 cm and >2 cm from the tumour edge (PLS-1, PLS-2 and RLS, respectively). The influence of tumour-associated factors was evaluated. The area under the receiver operating characteristic curve (AUC) for each value was analysed to diagnose cirrhosis. RESULTS: PLS-1 was higher than PLS-2, which was even higher than RLS (p < 0.001). The AUCs of PLS-1, PLS-2, RLS and SS for diagnosing cirrhosis were 0.760, 0.833, 0.940 and 0.676, with the specificity of 75.7%, 67.6%, 90.3% and 77.4%, respectively. Tumour sizes, locations or types showed no apparent influence on 2D-SWE values except for RLS, which was higher in patients with primary hepatic carcinomas (p < 0.05). CONCLUSIONS: LS with tumours is best measured at >2 cm away from the tumour edge. SS measurement could be used as an alternative to LS measurement in the event of no available liver for detection. KEY POINTS: • Tumour-associated factors impact background liver stiffness assessment. • Background liver stiffness is best measured at >2 cm from tumour edge. • Spleen stiffness can be an alternative to assess background liver stiffness.

Efficacy of ultrasound-guided core needle biopsy in cervical lymphadenopathy: A retrospective study of 6,695 cases.

OBJECTIVES: To determine the diagnostic yield of ultrasound-guided core needle biopsy (US-CNB) in cervical lymphadenopathy and identify the factors influencing the diagnostic accuracy of US-CNB. METHODS: We retrospectively reviewed the records of 6,603 patients with cervical lymphadenopathy who underwent 6695 US-CNB procedures between 2004 and 2017. RESULTS: Adequate specimens were obtained in 92.19 % (6,172/6,695) of cases. Most lymph nodes (67.65 %) were malignant (metastatic carcinoma 4,131; lymphoma 398). The overall accuracy of US-CNB for differentiating benign from malignant lesions was 91.70 % (6,139/6,695). Among biopsies in which adequate material was obtained, the sensitivity, specificity and accuracy of US-CNB were 99.70 %, 100 % and 99.46 %, respectively. The success or failure of US-CNB for the diagnosis of lymphadenopathy was significantly correlated with node size, nature (malignant vs. benign), and location as well as penetration depth, but not with needle size (p = 0.665), number of core tissues obtained (p = 0.324), or history of malignancy (p = 0.060). There were no major procedure-related complications. CONCLUSIONS: US-CNB is a safe and effective method of diagnosing cervical lymphadenopathy, and our findings may help optimise the sampling procedure by maximising its diagnostic accuracy and preserving its minimally invasive nature. KEY POINTS: • US-CNB is useful for the diagnosis of cervical lymphadenopathy. • US-CNB is safe to perform on lymph nodes located near vital structures. • Larger, malignant, level IV lymph nodes yield sufficient tissue samples more easily.

Transvaginal Ultrasound-Guided Core Needle Biopsy of Pelvic Masses.

OBJECTIVES: This study assessed the efficacy and safety of transvaginal ultrasound (US)-guided core needle biopsy (CNB) for obtaining adequate pelvic mass samples for histologic analysis and evaluated factors that may affect biopsy success. METHODS: Two hundred cases underwent transvaginal US-guided CNBs for primary inoperable tumors, suspicion of metastases to the ovaries or peritoneum, recurrence, or other solid lesions in the pelvis. Biopsy samples were obtained from the pelvic cavity (67.0%), vaginal cuff or vaginal wall (17.5%), or peritoneal cake (15.5%). The potential influences of the biopsy site (pelvic cavity, vaginal cuff or vaginal wall, or peritoneal cake), vascularization, ascites, tumor size, and tumor type (inoperable, metastases, recurrence, or solid pelvic tumor) on the success of transvaginal US-guided CNB were evaluated by a univariate analysis. RESULTS: Adequate samples were obtained in 192 of 200 biopsies (96.0%), of which 190 yielded successful diagnoses (95.0%). The biopsy site had a significant effect on biopsy adequacy, as there was a significantly lower probability of obtaining satisfactory specimens for histologic verification from the peritoneal cake compared to pelvic tumors and the vaginal cuff or vaginal wall (P < .01). Adequacy was also affected by tumor size (P < .05) but not by vascularization, ascites, or tumor type. No complications occurred during the biopsy procedures. CONCLUSIONS: Transvaginal US-guided CNB is a safe and effective alternative to more invasive methods for evaluating pelvic lesions, such as laparoscopy and laparotomy.

Combined Hepatocellular Cholangiocarcinoma (Biphenotypic) Tumors: Potential Role of Contrast-Enhanced Ultrasound in Diagnosis.

OBJECTIVE: The objective of this study was to evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differentiating combined hepatocellular cholangiocarcinomas (CHCs) from hepatocellular carcinomas (HCCs) and intrahepatic cholangiocarcinomas (ICCs). MATERIALS AND METHODS: Thirty-three patients with pathologically confirmed CHC and matched control subjects with pathologically confirmed HCC (n = 30) or ICC (n = 32) who underwent preoperative CEUS from January 2005 to December 2015 were enrolled in this study. The CEUS images of the hepatic lesions were subjectively analyzed in consensus by two radiologists. The diagnostic performances were evaluated by ROC analysis. RESULTS: In the arterial phase, hyperenhancement was more common in CHCs (76%) and HCCs (100%) than in ICCs (22%), whereas in the late phase marked washout was more common in CHCs (76%) and ICCs (100%) than in HCCs (10%). Using marked washout in the late phase to differentiate CHC from HCC, the area under the ROC curve (AUC) was 0.829, and the sensitivity, specificity, and accuracy were 78%, 90%, and 83%, respectively. Using hyperenhancement in the arterial phase followed by marked washout in the late phase to distinguish CHC from ICC, the AUC value was 0.663, and the sensitivity, specificity, and accuracy were 55%, 78%, and 66%. CONCLUSION: Although the imaging features of CHC, HCC, and ICC on CEUS may overlap, CEUS could be used in the differential diagnosis of CHC from HCC and ICC.

Dose-response relationship in cisplatin-treated breast cancer xenografts monitored with dynamic contrast-enhanced ultrasound.

BACKGROUND: Exactly assessing tumor response to different dose of chemotherapy would help to tailor therapy for individual patients. This study was to determine the feasibility of dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of tumor vascular response to different dose cisplatin. METHODS: MCF-7 breast cancer bearing mice were treated with different dose of cisplatin in group B (1 mg/kg) and group C (3 mg/kg). A control group A was given with saline. Sequential CEUS was performed on days 0, 3 and 7 of the treatment, in which time-signal intensity curves were obtained from the intratumoral and depth-matched liver parenchyma. Peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion time-intensity curves and normalized with respect to the adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor cell density and microvascular density (MVD). RESULTS: Significant decreases in tumor normalized perfusion parameters were observed on day 3 in the high dose group and on day 7 in the low dose group. On day 7, nPE, nWiAUC, and nWiPI significantly decreased in group C and group B as compared with group A (P < 0.05), and further decreased in group C as compared with group B (P < 0.05). Significant decreases of tumor cell density and MVD were seen in treated group (group B and C) compared to control group (P < 0.05) and further decrease in group C compared to group B (P < 0.05). CONCLUSIONS: Dynamic CEUS for quantification of tumor perfusion could be used to evaluate tumor vascular response to different dose of chemotherapy.

Ultrasonic spectrum analysis for in vivo characterization of tumor microstructural changes in the evaluation of tumor response to chemotherapy using diagnostic ultrasound.

BACKGROUND: There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The purpose of this study was to determine the feasibility of ultrasonic spectral analysis for the in vivo characterization of changes in tumor microstructure in the evaluation of tumor response to chemotherapy using diagnostic ultrasound. METHODS: Experiments were approved by the regional animal care committee. Twenty-four MCF-7 breast cancer bearing nude mice were treated with adriamycin or sterile saline administered by intraperitoneal injection. Ultrasonic radio-frequency (RF) data was collected using a clinically available ultrasound scanner (6-MHz linear transducer). Linear regression parameters (spectral slope and midband-fit) regarding the calibrated power spectra from the RF signals were tested to monitor tumor response to treatment. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for assessment of the density of tumor cell nuclei. RESULTS: Treatment with adriamycin significantly reduced tumor growth in comparison with the control group (p = 0.003). Significant changes were observed in the ultrasonic parameters of the treated relative to the untreated tumors (p < 0.05). The spectral slope increased by 48.5%, from -10.66 ± 2.96 to -5.49 ± 2.69; the midband-fit increased by 12.8%, from -57.10 ± 7.68 to -49.81 ± 5.40. Treated tumors were associated with a significant decrease in the density of tumor cell nuclei as compared with control tumors (p < 0.001). CONCLUSIONS: Ultrasonic spectral analysis can detect changes in tumor microstructure after chemotherapy, and this will be helpful in the early evaluation tumor response to chemotherapy.

Contrast-enhanced US quantitatively detects changes of tumor perfusion in a murine breast cancer model during adriamycin chemotherapy.

BACKGROUND: Currently used morphologic criteria have limitations in assessing tumor response to chemotherapy because of the relatively slow tumor shrinkage as measured by conventional morphologic imaging. Functional imaging techniques show promising results in early assessment of tumor response to treatment. PURPOSE: To quantitatively detect changes in tumor perfusion during chemotherapy with contrast-enhanced ultrasound. MATERIAL AND METHODS: Twenty-three MCF-7 breast cancer bearing nude mice treated by either adriamycin (n = 11) or sterile saline (n = 12) were imaged before and after treatment with an ultrasound scanner after bolus injection of SonoVue. Regions of interest within the tumor were analyzed offline to determine perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), rise time (RT), wash-in rate (WiR), wash-in perfusion index (WiPI), and quality of fit (QOF). Hematoxylin and eosin was used to assess tumor cell density and immunohistochemical analysis was performed for evaluation of microvascular density (MVD). RESULTS: Treatment with adriamycin significantly reduced tumor growth in comparison to the control group (P < 0.001). There was no significant difference in perfusion parameters before treatment. Treatment with adriamycin resulted in a significant decrease in PE, WiAUC, WiR, and WiPI in comparison with control group (P < 0.01). The tumor cell density estimated by pathology slice was significantly lower in treated tumors than in control tumors after treatment (P < 0.001). Immunohistochemistry showed significant decreases of MVD in treated tumors as compared with control tumors (P < 0.001) after treatment. CONCLUSION: Quantitative contrast-enhanced ultrasound can detect the change of tumor perfusion after chemotherapy, which may enable early assess tumor response to chemotherapy.

Quantitative assessment of tumor blood flow changes in a murine breast cancer model after adriamycin chemotherapy using contrast-enhanced destruction-replenishment sonography.

OBJECTIVES: The purpose of the study was to detect tumor blood flow changes after chemotherapy with contrast-enhanced destruction-replenishment sonography. METHODS: Twenty-four MCF-7 breast cancer-bearing nude mice were included in this study. Animals received either adriamycin or sterile saline and underwent contrast-enhanced sonography before and after treatment using a destruction-replenishment technique. A monoexponential function, y = A(1 - e(-ßt)), was used to fit the replenishment kinetics, where the plateau signal intensity A reflects the percent blood volume; the time constant ß reflects the average speed of blood; and their product A*ß reflects the nutrient blood flow. Tumor blood perfusion was compared to measurements of cell density and microvascular density. RESULTS: Volumes of the treated tumors were significantly reduced after 7 days of adriamycin treatment compared with the control tumors (P < .001). Before adriamycin administration, there was no significant difference in blood perfusion between the treated and control groups (P > .05). Treatment with adriamycin resulted in a significant decrease in A, ß, and A*ß (P <.001) compared with the control tumors. The tumor cell density and microvascular density estimated by pathologic slices were significantly lower in the treated tumors than in the control tumors (P <.001). CONCLUSIONS: Quantification of tumor blood flow using contrast-enhanced destruction-replenishment sonography shows the potential to evaluate tumor responses to chemotherapy.

A modified radiofrequency ablation approach for treating distant lymph node metastasis in two patients with late-stage cancer.

Patients with late-stage cancer commonly have distant lymph node metastasis; however, poor health often contraindicates surgical treatment. Although the quality of life and overall survival for these patients are low, there is neither a consensus nor a guide for treatment. Ablation technique and surrounding tissue damage are two possible reasons for limited study of radiofrequency ablation in patients with superficial distant lymph node metastasis. Here, we report two patients treated successfully with ultrasound-guided radiofrequency ablation for superficial distant lymph node metastasis. In these patients, deionized water was injected to the surrounding tissues of the lymph node to decrease heat injury. Results from these patients suggest that radiofrequency ablation may play an important role in the treatment of patients with distant lymph node metastasis.

Liver hypertrophy and accelerated growth of implanted tumors in nonembolized liver of rabbit after left portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) has become a standard preoperative procedure to promote hypertrophy of the future remnant liver to reduce postoperative liver failure. Whether PVE accelerates tumor growth is still controversial. We developed a left PVE procedure and investigated its effect on liver hypertrophy and tumor growth in a rabbit liver tumor model. MATERIALS AND METHODS: VX2 tumors were implanted in both the external left and right middle lobe (the bilateral group) or in the external left lobe only (the unilateral group) of rabbit liver. Both groups were further divided into a PVE or a sham/control group. Tumor volume and tumor growth rate as volume relative increase were determined by ultrasound. Liver volume-to-body weight index, an index for liver volume, was compared. Serum HGF was measured by ELISA. RESULTS: In the bilateral PVE group, tumor volume and relative increase value in the nonembolized lobe were significantly (71% and 65%, respectively) greater than those in the control group at 5 d post-PVE. In the unilateral PVE group, liver volume-to-body weight index of the nonembolized lobes was significantly increased by 17%. Increase of serum HGF level after PVE was correlated well with both tumor growth and liver hypertrophy. CONCLUSIONS: Left PVE promoted both the growth of implanted tumors and liver hypertrophy in the nonembolized liver, in which serum HGF might play an important role.

The lesion detection efficacy of deep learning on automatic breast ultrasound and factors affecting its efficacy: a pilot study.

OBJECTIVES: The aim of this study was to investigate the detection efficacy of deep learning (DL) for automatic breast ultrasound (ABUS) and factors affecting its efficacy. METHODS: Females who underwent ABUS and handheld ultrasound from May 2016 to June 2017 (N = 397) were enrolled and divided into training (n = 163 patients with breast cancer and 33 with benign lesions), test (n = 57) and control (n = 144) groups. A convolutional neural network was optimized to detect lesions in ABUS. The sensitivity and false positives (FPs) were evaluated and compared for different breast tissue compositions, lesion sizes, morphologies and echo patterns. RESULTS: In the training set, with 688 lesion regions (LRs), the network achieved sensitivities of 93.8%, 97.2% and 100%, based on volume, lesion and patient, respectively, with 1.9 FPs per volume. In the test group with 247 LRs, the sensitivities were 92.7%, 94.5% and 96.5%, respectively, with 2.4 FPs per volume. The control group, with 900 volumes, showed 0.24 FPs per volume. The sensitivity was 98% for lesions > 1 cm3, but 87% for those ≤1 cm3 (p < 0.05). Similar sensitivities and FPs were observed for different breast tissue compositions (homogeneous, 97.5%, 2.1; heterogeneous, 93.6%, 2.1), lesion morphologies (mass, 96.3%, 2.1; non-mass, 95.8%, 2.0) and echo patterns (homogeneous, 96.1%, 2.1; heterogeneous 96.8%, 2.1). CONCLUSIONS: DL had high detection sensitivity with a low FP but was affected by lesion size. ADVANCES IN KNOWLEDGE: DL is technically feasible for the automatic detection of lesions in ABUS.

Quantitative assessment of tumor blood flow in mice after treatment with different doses of an antiangiogenic agent with contrast-enhanced destruction-replenishment US.

PURPOSE: To quantify tumor blood flow by using contrast material-enhanced destruction-replenishment ultrasonography (US) to evaluate tumor response to different doses of an agent for antiangiogenic treatment in hepatoma-bearing mice, with histologic measurements of microvascular density (MVD) as the reference standard. MATERIALS AND METHODS: Experiments were approved by the regional animal care committee. Mice bearing subcutaneous H22 hepatoma were treated with different doses of thalidomide, 100 mg/kg in group B and 200 mg/kg in group C. Group A (control group) was treated with 0.5% carboxylmethylcellulose. Treatment groups and the control group included 10 mice each. Contrast-enhanced US was used to evaluate the percentage of nonenhanced area, and contrast-enhanced destruction-replenishment US was used to evaluate tumor blood flow. Tumor blood flow was compared with measurements of MVD. Comparisons were made by using one-way analysis of variance and the post hoc least significant difference test for multiple comparisons. RESULTS: Contrast-enhanced gray-scale US showed significant increases in the percentage of nonenhanced area in group C (mean, 10.56% ± 7.25 [standard deviation]), as compared with groups A (mean, 2.40% ± 3.12; P = .004) and B (mean, 3.75% ± 5.55; P = .012). Contrast-enhanced destruction-replenishment US showed significant decreases of tumor blood flow in groups B and C, as compared with group A (P = .003 and P < .001, respectively), and the blood flow in group C was significantly lower than that of group B (P = .01). Immunohistochemical analysis revealed significant decreases of MVD in groups B and C, as compared with MVD in group A (P = .002 and P < .001, respectively); however, there was no significant difference in MVD between groups B and C (P = .21). CONCLUSION: Quantification of tumor blood flow by using contrast-enhanced destruction-replenishment US shows the potential to guide drug dosage during antiangiogenic therapy.

Contrast-enhanced gray-scale ultrasound for quantitative evaluation of tumor response to chemotherapy: preliminary results with a mouse hepatoma model.

OBJECTIVE: The purpose of this study was to quantify tumor blood perfusion with contrast-enhanced gray-scale ultrasound in the evaluation of tumor response to chemotherapy. MATERIALS AND METHODS: Mice bearing H22 hepatoma were treated with cisplatin or placebo by intraperitoneal injection. Contrast-enhanced gray-scale ultrasound was performed on day 8 after bolus injection of a lipid-based ultrasound contrast agent. Regions of interest within the tumor were analyzed offline to determine area under the curve, maximum intensity, perfusion index, mean transit time, time to peak, and quality of fit. Immediately after imaging, mice were euthanized, and tumor tissue was removed for fixation in 10% formalin solution. Microvascular density was measured after anti-CD34 staining. RESULTS: The volume of treated tumors was significantly smaller than that of control tumors (p < 0.001). Treatment with cisplatin resulted in a significant decrease in perfusion index and maximum intensity compared with control tumors (p < 0.05). There were no significant differences between control and treated tumors (p > 0.05) with respect to area under the curve, mean transit time, and time to peak. The microvascular density of treated tumors was significantly lower than that of control tumors (p < 0.001). CONCLUSION: Quantitative analysis of tumor blood perfusion with contrast-enhanced ultrasound can be used for noninvasive assessment of functional changes in tumors after chemotherapy.

Evaluation of the Extent of Mesorectal Invasion and Mesorectal Fascia Involvement in Patients with T3 Rectal Cancer With 2-D and 3-D Transrectal Ultrasound: A Pilot Comparison Study With Magnetic Resonance Imaging Findings.

The aim of this study was to determine the value of 2-D and 3-D transrectal ultrasound (TRUS) in assessing the extent of mesorectal invasion (EMI) and mesorectal fascia involvement (MRF+) in patients with T3 rectal tumours. We retrospectively evaluated 80 patients with T3 stage rectal cancer who were pre-operatively evaluated by 2-D and 3-D TRUS before neoadjuvant chemoradiotherapy by using magnetic resonance imaging (MRI) as a reference standard. The T3 stage was subdivided into T3 ab (EMI ≤5 mm) and T3 cd (EMI >5 mm). The consistency assessment of the T3 sub-staging and MRF+ was compared between 2-D and 3-D TRUS using Cohen's kappa statistic. The concordance of the T3 sub-staging based on EMI was excellent between the 3-D TRUS and MRI (κ = 0.84) and good between the 2-D TRUS and MRI (κ = 0.67). For the assessment of MRF+ (κ = 0.82), 3-D TRUS and MRI showed excellent concordance. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 3-D TRUS for MRF+ assessment was 95.3%, 86.5%, 89.1% and 94.1%, respectively. The agreement between 3-D TRUS and MRI for the assessment of T3 sub-staging and MRF status was better in low rectal cancer (both κ = 0.85) than in middle (κ = 0.79 and 0.77) rectal cancer. Compared with MRI, 3-D TRUS has more advantages in the sub-staging of T3 rectal cancer and the assessment of MRF+ than those of 2-D TRUS, especially in low rectal cancer. For patients with T3 rectal cancer, 3-D TRUS may well complement MRI for selecting the appropriate treatment.

Development of prognostic index based on autophagy-related genes analysis in breast cancer.

BACKGROUND: Autophagy is a self-digesting process that can satisfy the metabolic needs of cells, and is closely related to development of cancer. However, the effect of autophagy-related genes (ARGs) on the prognosis of breast cancer remains unclear. RESULTS: We first found that 27 ARGs were significantly associated with overall survival in breast cancer. The prognosis-related ARGs signature established using the Cox regression model consists of 12 ARGs that can be divided patients into high-risk and low-risk groups. The overall survival of patients with high-risk scores (HR 3.652, 2.410-5.533; P < 0.001) was shorter than patients with low-risk scores. The area under the receiver operating characteristic (ROC) curve for 1-year, 3-year, and 5-year survival rates were 0.739, 0.727, and 0.742, respectively. CONCLUSION: The12-ARGs marker can predict the prognosis of breast cancer and thus help individualized treatment of patients at different risks. METHODS: Based on the TCGA dataset, we integrated the expression profiles of ARGs in 1,039 breast cancer patients. Differentially expressed ARGs and survival-related ARGs were evaluated by computational difference algorithm and COX regression analysis. In addition, we also explored the mutations in these ARGs. A new prognostic indicator based on ARGs was developed using multivariate COX analysis.

Diagnostic value, safety, and histopathologic discrepancy risk factors for endoscopic forceps biopsy and transrectal ultrasound-guided core needle biopsy in rectum lesions.

BACKGROUND: Accurate preoperative pathologic diagnosis is very important for making appropriate therapeutic decisions for patients with rectal lesions. This study aimed (I) to determine diagnostic value and safety of endoscopic forceps biopsy (EFB) and transrectal ultrasound (TRUS)-guided core needle biopsy (CNB), and (II) to analyze the risk factors for their histopathologic discrepancies, with a particular focus in identifying the indicators for re-biopsy using TRUS-guided CNB after EFB. METHODS: We retrospectively reviewed the records of 102 patients who received EFB and TRUS-guided CNB before surgery. The histopathologic concordance and risk factors for underdiagnosis by EFB and TRUS-guided CNB were analyzed. RESULTS: Compared with postoperative pathology, the histopathologic discrepancy rate of EFB and TRUS-guided CNB was 51.0% (52/102 lesions) and 8.8% (9/102 lesions), respectively. The kappa value for consistency with postoperative pathology findings was 0.420 for EFB and 0.876 for TRUS-guided CNB. The multivariate analyses and receiver operating characteristic (ROC) curve indicated that lesions thickness ≥13.5 mm [OR 1.080 (95% CI: 1.021-1.142), P=0.007] and flat/depressed shape [OR 0.206 (95% CI: 0.076-0.564), P=0.002] were significantly associated with histopathologic discrepancies in EFB. CONCLUSIONS: EFB was of limited clinical value in identifying the preoperative diagnosis of rectal lesions. Lesions thickness and flat/depressed shape at EFB were independent risk factors for pathologic discrepancies. TRUS-guided CNB may serve as a safe and effective supplement to routine EFB.

Ultrasound elastography as an imaging biomarker for detection of early tumor response to chemotherapy in a murine breast cancer model: a feasibility study.

OBJECTIVE: This study investigated the feasibility of using strain elastography (SE) and real time shear wave elastography (RT-SWE) to evaluate early tumor response to cytotoxic chemotherapy in a murine xenograft breast cancer tumor model. METHODS: MCF-7 breast cancer-bearing nude mice were treated with either cisplatin 2 mg kg-1 plus paclitaxel 10 mg kg-1 (treatment group) or sterile saline (control group) once daily for 5 days. The tumor elasticity was measured by SE or RT-SWE before and after therapy. Tumor cell density was assessed by hematoxylin and eosin staining, and the ratio of collagen fibers in the tumor was evaluated by Van Gieson staining. The correlation between tumor elasticity, as determined by SE and SWE, as well as the pathological tumor responses were analyzed. RESULTS: Chemotherapy significantly attenuated tumor growth compared to the control treatment (p < 0.05). Chemotherapy also significantly increased tumor stiffness (p < 0.05) and significantly decreased (p < 0.05) tumor cell density compared with the control. Moreover, chemotherapy significantly increased the ratio of collagen fibers (p < 0.05). Tumor stiffness was positively correlated with the ratio of collagen fibers but negatively correlated with tumor cell density. CONCLUSION: The study suggests that ultrasound elastography by SE and SWE is a feasible tool for assessing early responses of breast cancer to chemotherapy in our murine xenograft model. Advances in knowledge: This study showed that the tumor elasticity determined by ultrasound elastography could be a feasible imaging biomarker for assessing very early therapeutic responses to chemotherapy.

Comparison of contrast enhanced ultrasound and contrast enhanced CT or MRI in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma: a multi-center study in China.

To evaluate the ability of contrast enhanced ultrasound (CEUS) in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma (HCC) in comparison with contrast enhanced computed tomography (CECT) and/or magnetic resonance imaging (CEMRI). A total of 151 patients were enrolled in the study. Before the radio-frequency (RF) or microwave ablation treatment, tumor vascularity was assessed in 139 patients with three imaging modalities i.e., US (139 exams), CEUS (139 exams) and CECT (103 exams)/CEMR (36 exams). CEUS examination was performed using a sulphur hexafluoride-filled microbubble contrast agent (SonoVue((R)), Bracco, Milan, Italy) and real-time contrast-specific imaging techniques. Within 30 +/- 7 d after the ablation procedure, 118/139 patients were monitored to assess the tumor response to treatment. Before ablation, contrast enhancement within tumor was observed in 129/139 (92.8%) patients with CEUS and 133/139 (95.7%) patients with CECT/CEMRI. Compared with CECT/CEMRI, CEUS sensitivity and accuracy in detecting tumor vascularity were 97.0% and 94.2%, respectively. One month after treatment, no enhancement was seen in 110/118 (93.2%) both on CEUS and CECT/CEMRI. Concordance between CEUS and CECT/CEMR on the presence of residual vascularization was obtained in four patients (true positive). The specificity and accuracy of CEUS in detecting tumor vascularity were 98.2% and 96.6%, respectively. The periprocedural impact of SonoVue administration on the assessment of treatment extent was also evaluated in a subgroup of patients and CEUS showed its superiority compared with baseline US in defining treatment outcome. In conclusion, in the detection of HCC tumor vascularity and assessment of response to thermal ablation after 1 month, real time CEUS provided results comparable to those obtained with CECT/CEMRI. CEUS examination proved to be a safe and easy to access procedure, with potential for diagnostic impact in the clinical practice.

Genetic variants of cell cycle pathway genes predict disease-free survival of hepatocellular carcinoma.

Disruption of the cell cycle pathway has previously been related to development of human cancers. However, associations between genetic variants of cell cycle pathway genes and prognosis of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we evaluated the associations between 24 potential functional single nucleotide polymorphisms (SNPs) of 16 main cell cycle pathway genes and disease-free survival (DFS) of 271 HCC patients who had undergone radical surgery resection. We identified two SNPs, i.e., SMAD3 rs11556090 A>G and RBL2 rs3929G>C, that were independently predictive of DFS in an additive genetic model with false-positive report probability (FPRP) <0.2. The SMAD3 rs11556090G allele was associated with a poorer DFS, compared with the A allele [hazard ratio (HR) = 1.46, 95% confidential interval (95% CI) = 1.13-1.89, P = 0.004]; while the RBL2 rs3929 C allele was associated with a superior DFS, compared with the G allele (HR = 0.74, 95% CI = 0.57-0.96, P = 0.023). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had a significant shorter DFS (Ptrend  = 0.0001). Further analysis using receiver operating characteristic (ROC) curves showed that the model including the NUGs and known prognostic clinical variables demonstrated a significant improvement in predicting the 1-year DFS (P = 0.011). Moreover, the RBL2 rs3929 C allele was significantly associated with increased mRNA expression levels of RBL2 in liver tissue (P = 1.8 × 10-7 ) and the whole blood (P = 3.9 × 10-14 ). Our data demonstrated an independent or a joint effect of SMAD3 rs11556090 and RBL2 rs3929 in the cell cycle pathway on DFS of HCC, which need to be validated by large cohort and biological studies.