Contrast-enhanced ultrasonography assessment of gastric cancer response to neoadjuvant chemotherapy

AIM:To quantitatively assess the ability of double contrast-enhanced ultrasound(DCUS) to detect tumor early response to pre-operative chemotherapy.METHODS:Forty-three patients with gastric cancer treated with neoadjuvant chemotherapy followed by curative resection between September 2011 and February 2012 were analyzed.Pre-operative chemotherapy regimens of fluorouracil + oxaliplatin or S-1 + oxaliplatin were administered in 2-4 cycles over 6-12 wk periods.All patients underwent contrast-enhanced computed tomography(CT) scan and DCUS before and after two courses of pre-operative chemotherapy.The therapeutic response was assessed by CT using the response evaluation criteria in solid tumors(RECIST 1.1) criteria.Tumor area was assessed by DCUS as enhanced appearance of gastric carcinoma due to tumor vascularity during the contrast phase as compared to the normal gastric wall.Histopathologic analysis was carried out according to the Mandard tumor regression grade criteria and used as the reference standard.Receiver operating characteristic(ROC) analysis was used to evaluate the efficacy of DCUS parameters in differentiating histopathological responders from non-responders.RESULTS:The study population consisted of 32 men and 11 women,with mean age of 59.7 ± 11.4 years.Neither age,sex,histologic type,tumor site,T stage,nor N stage was associated with pathological response.The responders had significantly smaller mean tumor size than the non-responders(15.7 ± 7.4 cm vs 33.3 ± 14.1 cm,P < 0.01).According to Mandard's criteria,27 patients were classified as responders,with 11(40.7%) showing decreased tumor size by DCUS.In contrast,only three(18.8%) of the 16 non-responders showed decreased tumor size by DCUS(P < 0.01).The area under the ROC curve was 0.64,with a 95%CI of 0.46-0.81.The effects of several cut-off points on diagnostic parameters were calculated in the ROC curve analysis.By maximizing Youden's index(sensitivity + specificity-1),the best cut-off point for distinguishing responders from non-responders was determined,which had optimal sensitivity of 62.9% and specificity of 56.3%.Using this cut-off point,the positive and negative predictive values of DCUS for distinguishing responders from non-responders were 70.8% and 47.4%,respectively.The overall accuracy of DCUS for therapeutic response assessment was 60.5%,slightly higher than the 53.5% for CT response assessment with RECIST criteria(P = 0.663).Although the advantage was not statistically significant,likely due to the small number of cases assessed.DCUS was able to identify decreased perfusion in responders who showed no morphological change by CT imaging,which can be occluded by such treatment effects as fibrosis and edema.CONCLUSION:DCUS may represent an innovative tool for more accurately predicting histopathological response to neoadjuvant chemotherapy before surgical resection in patients with locally-advanced gastric cancer.

Interaction between encapsulated microbubbles:A finite element modelling study

Theoretical studies on the multi-bubble interaction are crucial for the in-depth understanding of the mechanism behind the applications of ultrasound contrast agents （UCAs） in clinics. A two-dimensional （2D） axisymmetric finite element model （FEM） is developed here to investigate the bubble-bubble interactions for UCAs in a fluidic environment. The effect of the driving frequency and the bubble size on the bubble interaction tendency （viz., bubbles＇ attraction and repulsion）, as well as the influences of bubble shell mechanical parameters （viz., surface tension coefficient and viscosity coefficient） are discussed. Based on FEM simulations, the temporal evolution of the bubbles＇ radii, the bubble-bubble distance, and the distribution of the velocity field in the surrounding fluid are investigated in detail. The results suggest that for the interacting bubble-bubble couple, the overall translational tendency should be determined by the relationship between the driving frequency and their resonance frequencies. When the driving frequency falls between the resonance frequencies of two bubbles with different sizes, they will repel each other, otherwise they will attract each other. For constant acoustic driving parameters used in this paper, the changing rate of the bubble radius decreases as the viscosity coefficient increases, and increases first then decreases as the bubble shell surface tension coefficient increases, which means that the strength of bubble-bubble interaction could be adjusted by changing the bubble shell visco-elasticity coefficients. The current work should provide a powerful explanation for the accumulation observations in an experiment, and provide a fundamental theoretical support for the applications of UCAs in clinics.