## 4 Discussion
### Results of This Systematic Review and Meta-Analysis  
Our systematic search identified a limited number of studies and investigated the application of elastography in renal lesions, with significant heterogeneity in terms of study aims, design, instrumentation characteristics, target population, and results. First of all, we found great variability regarding the total number of patients and lesions included in the studies and also regarding the types of lesions. The most numerous lesions were RCC (some studies distinguish between different histotypes) and AML, and these data are consistent with the literature [6; 39]. For other types of solid renal masses, it was not possible to meta-analyze elasticity values due to the scarcity and sparseness of the data. Second, further variability among studies is clearly attributable to the presence of different reference standards, as histological confirmation was usually available only for malignant lesions, while the others were usually referred to as follow-up, and only an imaging-based diagnosis was available. Other factors to consider regarding US elastography techniques (SWE and SE) and the lack of protocol uniformity among different research groups (including ROI size and placement, number of samplings per lesion, patient positioning, etc.). SWE, especially 2D-SWE, is nowadays established as the preferred technique, as it presents some advantages [10]: it does not require manual compression, it provides both a point and a 2D-quantitative estimation of the tissue elasticity, and it visualizes a color-coded 2D map when superimposed on B-mode visualization, which can be matched to a \"confidence threshold\" map to visually appreciate in real time the reliability of the measurements. Indeed, although theoretically, we should expect increased stiffness at SWE in malignant lesions--as a consequence of high cellularity--some studies among those using SWE have unexpectedly presented opposite results [19; 22]. Consequently, when comparing the mean stiffness values between RCC and AML in SWE studies, we found a general trend of greater stiffness in RCC than in AML, but this trend was not statistically significant at an indirect comparison ([PERSON]'s Q test \(p=0.055\)) or at a direct comparison (summary SMD 0.38, 95% CI \(-0.09\)-\(0.86\), \(p=0.114\)). Conversely, it should be noted that all studies using SE consistently showed higher strain ratio values in RCC compared to AML, with these results confirmed both at an indirect ([PERSON]'s Q test \(p=0.014\)) and direct comparison, where strain ratios of RCC were shown to be significantly higher (\(p=0.021\)). The strain ratio is a dimensionless semi-quantitative measure that takes into account the differential displacement between the lesion and its surroundings (since the second ROI is positioned on the normal renal parenchyma). Even if it is not possible to estimate the magnitude of the stress applied, which could be very different between the various operators--as the stiffness of the lesionsis always evaluated in comparison with the surrounding parenchyma, which is subjected to the same stress--this factor could contribute to explain the higher consistency of the SE results compared to SWE, in which ROIs were placed only within the lesion. To explain these results, another aspect that could be considered is the intrinsic heterogeneity of lesions that can affect the elasticity values. One might expect that larger lesions would be mostly heterogeneous due to the development of necrotic areas, which are not always easy to detect in US (otherwise, they should be excluded, as US elastography cannot be performed on cystic lesions). However, at meta-regression among studies employing SWE, we even observed the opposite effect of lesion size on RCC stiffness and no effect of lesion size on AML stiffness, which was instead influenced by patients' age.