Diagnostic Performance Of Contrast-enhanced Ultrasound For Clear Cell Renal Cell Carcinoma: A Meta-analysis

Background:Renal cell carcinoma（RCC）is the main source of renal malignant tumors,and its most common subtype is clear cell renal cell carcinoma（cc RCC）.cc RCC has a high degree of malignancy and is prone to peripheral infiltration or metastasis.At present,partial or total nephrectomy is the main treatment for focal cc RCC with a good prognosis.However,when metastasis occurs,the best opportunity for surgery is missed,and systemic targeted or immunotherapy is mainly adopted.Patients with advanced metastases tend to have low survival rate.Therefore,early accurate diagnosis and reasonable treatment can help to improve the patient prognosis.Nowadays,various imaging methods play a key role in the diagnosis and differential diagnosis of cc RCC.Enhanced CT examination using contrast agent imaging technology can contribute to the identification of benign and malignant renal tumors as well as renal cancer typing.But this examination is radioactive,also does not suitable for patients with iodine contrast agent allergy or renal insufficiency.Enhanced MRI examination also facilitates the detection and diagnosis of cc RCC.However,this examination is not applicable to patients with claustrophobia,equipped with pacemakers,or gadolinium contrast allergy.At the same time,due to its high cost and long scanning time,it is not the first choice in clinical applications.Contrast-enhanced ultrasound（CEUS）examination can dynamically and continuously collect the enhancement process of the lesion in real time.It can clearly display the perfusion status of microvessels,as well as the situation of ischemia and necrosis in tumors with a diameter of less than 1cm.CEUS effectively makes up for the deficiency of enhanced CT and enhanced MRI due to its economic convenience,low rate of allergic reaction and no renal toxicity.CEUS has become an important tool for the diagnosis of cc RCC.Purpose:It aims to evaluate the accuracy of applying CEUS to diagnose cc RCC and discuss its value in clinical application.Methods:Using the search terms of"Clear Cell Renal Cell Carcinoma","Contrast-enhanced Ultrasound","renal clear cell carcinoma",and"contrast enhanced ultrasound",we collected the relevant literature published on Pub Med,the Cochrane Library,CNKI and other three databases during 2005.1-2022.1.The literature was screened according to the inclusion and exclusion criteria.The quality assessment of diagnostic accuracy studies-2（QUADAS-2）cale was used to evaluate the quality of the included literature.The I~2values were used to quantify the heterogeneity between the original studies.Heterogeneity were considered not obvious when I~2is<50%,and obvious when I~2is>50%.When there is obvious heterogeneity,it is necessary to use the random effects model to merge the data and explore the potential factors leading to the heterogeneity.True positive,false positive,false negative,and true negative values from the original study were extracted for statistical analysis to evaluate the accuracy of the diagnostic test.Calculate the post-test probability by setting the pre-test probability to analyze the clinical application of the diagnostic test.This study used Review Manager 5.3 software,Meta-disc1.4 software and STATA 15.1 software for statistical analysis.Result:A total of 12 original studies were included in this Meta-analysis,including 1302patients with a total of 1324 lesions.The heterogeneity test results showed that the sensitivity I~2value was 78%（P<0.01）and the specificity I~2value was 67%（P<0.01）between the original studies,indicating significant heterogeneity.The effect sizes were combined,and the combined amount and their 95%confidence interval（CI）respectivelyshowed that the sensitivity was 84%（95%CI:78%-89%）,the specificity was 84%（95%CI:77%-90%）,and the positive likelihood ratio was 5.30（95%CI:3.48-8.08）),the negative likelihood ratio is 0.19（95%CI:0.13-0.27）,the diagnostic odds ratio is 28.44（95%CI:14.32-58.47）.The area under the summary receiver operator characteristic curve is 0.91.Assuming that the pre-test probability is 50%,the calculated post-test probability is 84%.Conclusion:CEUS diagnosis of cc RCC has high sensitivity and specificity,good diagnostic accuracy and high clinical application value.However,the results of this study have some heterogeneity,and it is still necessary to collect more high-quality studies and accumulate a larger sample size for verification.