Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status.

BACKGROUND: The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. METHODS: We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. RESULTS: Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. CONCLUSIONS: Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

[Molecular Mechanisms of Breast Nodule Stiffness].

The texture of breast nodules has always the focus of clinical palpation,and the stiffness of breast nodules has been a hot research topic of ultrasound elastography. Both texture and stiffness are based on the principle that malignant tissue is stiffer than benign tissues,but the underlying mechanisms of breast nodule stiffness is not yet confirmed. Breast nodule stiffness is affected by both substance and mesenchyme,and the latter is an important factor. Collagen,as the major composition of the extra cell matrix,plays an important role in breast nodule stiffness. This review summarizes the molecular mechanisms of intracellular and extracellular changes in the formation of breast nodules.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion.

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Shear-Wave Elastography: Could it be Helpful for the Diagnosis of Non-Mass-Like Breast Lesions?

The goal of this study was to analyze the diagnostic performance of shear wave elastography (SWE) in differentiation of benign and malignant non-mass-like (NML) breast lesions. Three hundred sixteen consecutive breast lesions in 305 patients who have been scheduled for ultrasound (US)-guided core needle biopsy or vacuum-assisted biopsy or surgical excision between January 2013 and August 2013 were initially included in this study. Finally, 63 patients with 67 lesions classified as NML lesions comprised our study population. The features of SWE and its diagnostic performance in NML lesions were analyzed. Among the 67 NML lesions, 33 were malignant and 34 were benign. The maximum elastic modulus, mean elastic modulus, minimum elastic modulus, elastic modulus ratio and stiff rim sign of the malignant lesions were all significantly higher than those of benign lesions (p < 0.05). The combination of conventional US with maximum elastic modulus and stiff rim sign got significantly higher diagnostic specificity and positive predictive value (PPV) than conventional US (p < 0.05 for both). In the benign lesions, 23 (67.6%) unnecessary biopsies could have been eliminated after the combination of conventional US and SWE. SWE could increase diagnostic specificity and positive predictive values of NML breast lesions. The combination of conventional US and SWE could reduce unnecessary benign biopsies of NML lesions.

Percutaneous Removal of Benign Breast Lesions with an Ultrasound-guided Vacuum-assisted System: Influence Factors in the Hematoma Formation.

Objective To explore the influence factors in hematoma formation after removing benign breast lesions with an ultrasound-guided vacuum-assisted system.Methods A total of 232 females with 312 benign breast masses received excisional biopsy with ultrasound- guided vacuum-assisted system. The pathology of patients, Results of hematoma development and outcome, influence factors for hematoma occurrence (nodule size, nodule location, number of nodule, breast shape, menstrual period, efficacy time of bandage, and application of hemostatic agents during the procedure) were recorded.Results Pathologic examination revealed fibroadenomas in 138 lesions, fibroadenosis in 127 lesions, intraductal papillomas in 39 lesions, inflammatory change in 4 lesions, retention cyst of the breast in 3 lesions, and benign phyllodes tumor in 1 lesion. Thirty hematomas were observed in patients (9.6%). Finally, 97.0% hematomas were absorbed completely within 6 months follow-up. The incidence rates of hematoma were increased by 24.7%, 10.0%, 63.2%, 13.9% in the nodule diameter larger or equal to 25 mm group, removal of larger or equal to two nodules once time from one patient group, menstrual period group, and larger and loose breast group, respectively (all P<0.05). However, the incidences were decreased by 60.6% in the bandage performed for 12-24 hours or beyond 24 hours group (P<0.05). The multiple logistic regression models revealed that nodule size (χ2=15.227, P<0.001), number of nodule (χ2=7.767, P=0.005), menstrual period (χ2=24.530, P<0.001), and breast shape (χ2=9.559, P=0.002) were independent risk factors associated with hematoma occurrence, but efficacy time of bandage was a protective factor associated with hematoma occurrence.Conclusion The occurrence of hematoma after the minimally invasive operation was associated with nodule size, number of nodule, menstrual period, breast shape, and efficacy time of bandage.

[Construction of Nude Mouse Model of Triple Negative Breast Cancer and Value of Thermal Tomography].

OBJECTIVE: To explore the early detection of breast cancer by ultrasonic imaging and thermal tomography of luciferase or green fluorescent protein (GFP)-labeled MDA-MB-231 breast cancer cell line-xenografts in nude mice. METHODS: Fluorescence-tagged lentiviral vectors were transfected into the triple-negative breast cancer cell line MDA-MB-231. These cells were implanted either subcutaneously under the right breast pad or intravenously into the tail vein of nude BALB/C mice. Thermal tomography and ultrasound imaging were used to detect tumor formation and to monitor tumor growth and metastasis in vivo. RESULTS: Triple negative breast cancer cell line-xenografts were used to successfully construct an orthotopic nude mice model of breast cancer metastasis in the peritoneum. Thermal tomography and ultrasound imaging were used together to detect small tumors. Thermal tomography imaging detected small tumors earlier than ultrasound imaging. CONCLUSIONS: Thermal tomography can be used to monitor changes in tumor growth and detect abnormal tissue. Therefore, it can serve as a convenient,rapid,sensitive, and reliable technique for early screening of human breast cancer.

Evaluation of Elastic Stiffness in Healing Achilles Tendon After Surgical Repair of a Tendon Rupture Using In Vivo Ultrasound Shear Wave Elastography.

BACKGROUND There has been no published report assessing the mechanical properties of a repaired Achilles tendon after surgery using shear wave elastography (SWE). The aim of this study was to investigate the changes in mechanical properties of the healing Achilles tendon after surgical repair of a tendon rupture using ultrasound SWE and how these changes correlate with tendon function. MATERIAL AND METHODS Twenty-six patients who underwent surgical repair for Achilles tendon rupture were examined with ultrasound SWE coupled with a linear array transducer (4-15 MHz). The elasticity values of the repaired Achilles tendon in a longitudinal view were measured at 12, 24, and 48 weeks postoperatively. Functional outcomes were assessed with the American Orthopedic Foot and Ankle Society (AOFAS) rating system at 12, 24, and 48 weeks postoperatively. General linear regression analysis and correlation coefficients were used to analyze the relationship between elasticity and the AOFAS score. RESULTS There were significant differences with respect to the mean elasticity values and functional scores of the repaired Achilles tendon at 12, 24, and 48 weeks postoperatively (all P<0.05). Tendon function was positively correlated with the elasticity of the repaired Achilles tendon (P=0.0003). CONCLUSIONS Our findings suggest that SWE can provide biomechanical information for evaluating the mechanical properties of healing Achilles tendon and predict Achilles tendon function.

[Research on Modeling Method for Chlorophyll Content Fine Measurement Based on Neural Network].

Aiming at SPAD values of living plant leaf chlorophyll content affected easily by the blade thickness, water content, etc, a fine retrieval method of chlorophyll content based on multiple parameters of neural network model is presented. The SPAD values and water index (WI) of leaves were obtained by the leaf transmittance under the irradiation of light central wavelength in 650 nm, 940 nm, 1450 nm respectively. Meanwhile, the corresponding blade thickness is got by micrometer and the chlorophyll content is measured by spectrophotometric method. To modeling samples, the single parameter model between SPAD values and chlorophyll content was built and the nonlinear model between WI, thickness, SPAD values and chlorophyll content was established based on BP neural network. The predicted value of chlorophyll content of test samples were calculated separately by two models, and the correlation and relative errors were analyzed between predicted values and actual values. 340 samples of three different plant leaves were tested by the method described above in experiment. The results showed that compared with single parameter model, the prediction accuracy of three different plant samples were improved in different degrees, the average absolute relative error of chlorophyll content of all pooled samples predicted by BP neural network model reduced from 7.55% to 5.22%. The fitting determination coefficient is increased from 0.83 to 0.93. The feasibility were verified in this paper that the prediction accuracy of living plant chlorophyll content can improved effectively using multiple parameter BP neural network model.

Performance of Ultrasonic Shear Wave Elastography in Assessing Benign and Malignant Breast Lesions.

OBJECTIVE: To determine the best shear wave elastography (SWE) quantitative parameters including the maximum elasticity (Emax), mean elasticity(Emean), minimum elasticity, standard deviation and ratio of Emean (Eratio) in assessing benign and malignant breast lesions. METHODS: Totally 302 breast lesions underwent conventional ultrasound and SWE. Each lesion was classified according to ultrasound Breast Imaging Reporting and Data System (BI-RADS). The receiver operating characteristic(ROC) curves were used to determine the cut-off values of SWE quantitative parameters and to suggest breast lesions as benign or malignant. The sensitivity,specificity and the Youden index (sum of sensitivity and specificity minus 1) of SWE quantitative parameters were compared,and then the sensitivity,specificity and the Youden index of the combinations of each SWE parameters in assessing breast lesions were compared. RESULTS: The sensitivity,specificity and the Youden index of the Emax were 0.87,0.97 and 0.84,which were higher than other SWE parameters (all P<0.01). The sensitivity, specificity and the Youden index of Emax combined with ultrasound BI-RADS were 0.86,0.97 and 0.83, which were higher than other combinations (all P<0.01). CONCLUSIONS: Compared with other parameters, Emax has the best performance in assessing breast lesions. It can be used as an important quantitative indicator for the evaluation of benign and malignant breast lesions.

Non-mass-like lesions on breast ultrasound: classification and correlation with histology.

PURPOSE: Owing to advances in ultrasound (US) technology, optimal US techniques with a high-frequency transducer can identify more and more breast lesions. However, some lesions show up as non-mass-like lesions, which are difficult to be correctly identified and often result in missed diagnosis and misdiagnosis. The purpose of the present study was to develop a classification of the US features of non-mass-like breast lesions correlated with pathology, so as to improve the diagnostic accuracy of US in non-mass-like breast lesions. MATERIALS AND METHODS: A total of 854 breast lesions in 836 consecutive women scheduled for US-guided core-needle biopsy or US-guided vacuum-assisted biopsy between May 2008 and October 2011 were initially included in this study. Finally, 80 breast lesions in 78 women were classified as non-mass-like lesion and included in this study. The US features of the 80 non-mass-like breast lesions were classified and their correlation with pathology was analysed. RESULTS: Of the 80 non-mass-like breast lesions, 43 cases (53.8 %) were malignant and 37 cases (46.2 %) were benign. Fifty-two cases (73.7 %) appeared as a hypoechoic area, 22 cases (21.1 %) appeared as a hypoechoic area with sporadic or clustered microcalcification, four cases appeared as architectural distortion, and two cases appeared as solid echogenicity within a duct. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of US for non-mass-like breast lesions were 71.25, 95.35, 43.24, 66.13 and 88.89 %, respectively. The finding of a hypoechoic area with microcalcification showed a statistically significant association with malignant lesions and its positive predictive value for carcinoma was 78.26 %. CONCLUSION: Non-mass-like breast lesions usually appeared as a hypoechoic area or a hypoechoic area with microcalcification. The finding of a hypoechoic area with microcalcification had a close correlation with malignant lesions. US had a high sensitivity but a low specificity in the diagnosis of non-mass-like breast lesions and a definitive diagnosis requires a US-guided biopsy.

A set of shear wave elastography quantitative parameters combined with ultrasound BI-RADS to assess benign and malignant breast lesions.

The goal of this study was to determine whether a combination of shear wave elastography (SWE) quantitative parameters could improve the accuracy of ultrasonography in the differentiation of benign and malignant breast lesions. Two hundred seventy-nine breast lesions in 251 women were evaluated with ultrasonography and SWE; pathologic results of all lesions were available. Each lesion was classified according to the Breast Imaging Reporting and Data System (BI-RADS) for ultrasound. SWE quantitative parameters, including maximum elastic value (Emax), mean elastic value (E mean), standard deviation (SD) and ratio of E mean of the lesion to E mean of the surrounding parenchyma (E ratio), were recorded. A receiver operating characteristic curve was used to determine their cutoff values. When any of the four parameters was equal to or higher than the cutoff value, the set of SWE parameters was counted as positive. When both BI-RADS and the set were positive, lesions were evaluated as positive for malignancy. We compared the performance of this combination with use of BI-RADS, Emax, E mean, SD or E ratio alone and also with the combination of BI-RADS and Emax for benign/malignant differentiation. The combination of Emax, E mean, SD, or E ratio with BI-RADS had a sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index of 0.967, 0.912, 0.908, 0.969, 0.938 and 0.879, respectively. The accuracy was the highest (p < 0.01) without loss of sensitivity. Combining a set of SWE quantitative parameters (E max, E mean, SD and E ratio) could improve the accuracy of ultrasonography in differentiation of benign from malignant breast lesions, without loss of sensitivity.

Study of quantitative elastography with supersonic shear imaging in the diagnosis of breast tumours.

PURPOSE: This study was undertaken to evaluate the value of quantitative elastography in the diagnosis of breast tumours. MATERIALS AND METHODS: Conventional ultrasound (US) and quantitative elastography were performed in 108 women with 114 breast lesions by two experienced radiologists, and pathological results were available in all cases. For each lesion, the maximum, mean, and minimum (min) elasticity and elasticity ratio between lesions and surrounding tissue were measured. The Breast Imaging Reporting and Data System (BI-RADS) categories were assessed with conventional US in all lesions. RESULTS: Malignant lesions exhibited significantly higher maximum and mean elasticity (111.57 ± 69.29 kPa and 54.49 ± 33.70 kPa) than did benign lesions (59.00 ± 45.3 kPa and 36.64 ± 26.18 kPa) (p<0.01). For maximum elasticity versus BI-RADS, performance results were sensitivity 60.9 % vs. 78.3%, specificity 85.3% vs. 98.5%, positive predictive value (PPV) 73.7% vs. 97.3 %, negative predictive value (NPV) 76.3% vs. 87.0 % and accuracy 75.4% vs. 90.3%. BI-RADS had significantly better accuracy than maximum elasticity (p<0.01). Maximum and mean elasticity of invasive ductal carcinoma (IDC) were significantly higher than those of fibroadenoma (p<0.01), whereas the difference was not statistically significant with fibroadenosis, papilloma and inflammation (p>0.01). Maximum and mean elasticity and elasticity ratio of BI-RADS 5 were all significantly higher than those of BI-RADS 3 (p<0.01). Reliability for maximum and mean elasticity were almost perfect [intraclass correlation coefficients (ICC)=0.87 and 0.79]. CONCLUSIONS: Shear-wave elastography gives quantitative elasticity information that could potentially help in breast-lesion characterisation, although it cannot replace conventional BI-RADS in the differentiation of breast lesions.

Percutaneous excisional biopsy of clinically benign breast lesions with vacuum-assisted system: comparison of three devices.

PURPOSE: The aim of this study was to compare three devices in percutaneous excisional biopsy of clinically benign breast lesions in terms of complete excision rate, duration of procedure and complications. MATERIALS AND METHODS: In a retrospective study from March 2005 to May 2009, 983 lesions underwent ultrasound-guided excisional biopsy with three vacuum-assisted systems, respectively. The lesions were category 3 lesions as determined by ultrasound imaging according to Breast Imaging Reporting and Data System (BI-RADS) (n=951) or had been confirmed as benign by a previous core needle biopsy (n=32). The completely excision rate, duration of procedure and complications (hematoma, pain and ecchymosis) were recorded. RESULTS: 99.7% (980/983) lesions were demonstrated to be benign by pathology after percutaneous excisional biopsy. The overall complete excision rate was 94.8% (932/983). In lesions whose largest diameter equal to or larger than 1.5cm, the complete excision rates of EnCor(®) group (97.8%, 348/356) and Mammotome(®) group (97.2%, 139/143) were significantly higher than that of Vacora(®) group (91.9%, 445/484) (P<0.05). The EnCor(®) group (6.6±6.5min) had a significant less duration than Mammotome(®) (10.6±9.3min) and Vacora(®) group (25.6±23.3min) (P<0.05). Hematoma occurred more in EnCor(®) group and Mammotome(®) group than in Vacora(®) group (P<0.05). CONCLUSIONS: All these three vacuum-assisted systems are highly successful for excisional biopsy of benign breast lesions.