**3. Clinical applications**

Both strain and shear-wave elastography are available in the EUS setting for pancreatic disease [20, 21]. One of the major differences between these techniques is that when strain elastography is used only relative values are obtained as this is only a semiquantitative method, whereas shear-wave elastography produces absolute values, which may be more relevant. Thus, color pattern assessment with strain ratio and strain histogram analysis, as well as definite values for shear wave elastography may aid for pancreatic disease assessment and may represent an adjuvant method to confirm the diagnosis.

#### **3.1 Pancreatic masses**

There is always room for techniques improvement when discussing pancreatic tumors. Even though EUS-FNB is now considered the main method to confirm the diagnosis of a pancreatic tumor [22], elastography might aid in providing a larger panel when imaging examinations are performed.

Solid pancreatic lesions were classified by qualitative elastography into four different patterns presumably with their correspondent, normal tissue—green pattern, malignant tumor—mostly blue with small green areas and red lines, inflammatory mass—green with yellow and red lines or neuroendocrine tumor—homogeneous blue pattern [23]. When performing this procedure, it is important to avoid a smaller ROI, as the measurements will show a relative elasticity difference. Thus, the ROI should be large enough to include the tumor as well as normal adjacent tissue, and this is easily achievable in a clinical setting with a ratio of 50% for lesions and 50% for nearby tissues [24].

Along with the first study in 2006 [25], EUS was introduced as an optimistic technique that might be at least as useful as it was introduced in breast cancer. Moreover, due to the pancreatic adenocarcinoma characteristics as a tumor with high desmoplastic reaction, when performing EUS-E, the tumors should be much stiffer than the surrounding tissue [26]. However, no reliable correlation was successful so far with tumor grading.

Further on, the use of quantitative EUS-E suggested more reliable results, even though there were no differences in accuracy between these two techniques [27]. Iglesias-Garcia et al [28] mentioned that the strain ratio method had a higher accuracy (97.7%) and specificity (92.2%) than the qualitative analysis and that a cutoff value of the strain ratio higher than 6.04 with a lower elasticity index than 0.05% might be sensitive enough the difference between malignant and benign pancreatic tumors. He also concluded that this technique might properly differentiate from inflammatory masses with a sensitivity of 100% and a specificity of 96% and neuroendocrine tumors (sensitivity 100% and specificity 88%).

Histogram analysis also showed some promising results (**Figures 1** and **2**). In our own study published in 2008 [29], we reported a 91.4% sensitivity, 87.9% specificity, 88.9% positive predictive value (PPV), and 90.6% negative predictive value (NPV) for the diagnosis of pancreatic malignancies, based on a cutoff of 175. Even more, better results were obtained by Schrader et al [30], who obtained 100% sensitivity and 100% specificity for pancreatic ductal adenocarcinoma (PDAC) detection; however, they did mention the controls were patients with a normal pancreas. This might not be relevant, since chronic pancreatic or other masses would be the main objective to be compared with.

Currently, there are seven meta-analyses (**Table 1**) [31–37] that include strain EUS-E for pancreatic cancer and showed a specificity of 92–98% and a specificity of 67–76%. However, two studies assessed small pancreatic tumors of less than 15 and 20 mm, respectively, and pointed out that EUS-E might be confident in suggesting that PDAC is a stiff tumor [38, 39]. Kataoka et al [38] analyzed 126 cases of small pancreatic lesions associated or not with main pancreatic duct dilation. They concluded that a stiffness ratio was definitely higher for pancreatic cancer 62:3 vs. 29:32, *P* < 0.001. Also, when comparing lesions with PC vs. without main pancreatic duct dilation, the sensitivity (94 vs 100%), specificity (23 vs 60%), and predictive value (60 vs 100%) were different suggesting that a small lesion might be excluded from being pancreatic cancer without main pancreatic duct dilation with high confidence and concordance.

As this technique may be used as an adjuvant tool for pancreatic masses diagnosis, it may be included in a panel of procedures to enhance the diagnosis process. Combining EUS-E with contrast-enhanced endoscopic ultrasound (CEUS), it could help patients with a negative FNA, if a PDAC is strongly suspected. For EUS-FNA negative cases, we compared PDAC patients with chronic pancreatitis and suggested that a hypovascular, hard tumor might suggest a PDAC with 75.8% sensitivity, 85.2% specificity, 83.3% PPV, and 96.2% NPV [40].

A different approach was tested by Yamada et al [41], which tried to assess vascular invasion of PDAC using EUS-E. They defined vascular invasions as seen in EUS by their exerting pressure characteristics. They considered that if two tissues with different stiffness are in close contact, but not fixed, their border will move when compression is made, which will translate in EUS-E as a softer tissue with adjacent artifacts with red, yellow, and green. On the other hand, if their border moves at a time, they will not have any artifacts there, thus they might have a vascular invasion. EUS-E showed a high diagnostic ability with a sensitivity of 0.917 a specificity of 0.900, and

*Endoscopic Ultrasound Elastography: New Advancement in Pancreatic Diseases DOI: http://dx.doi.org/10.5772/intechopen.103890*

#### **Figure 1.**

*Multimodal EUS imaging of a solid pancreatic tumor, pancreatic adenocarcinoma. A EUS – Doppler imaging. B Contrast-enhanced ultrasound imaging. C. EUS-E imaging with strain histogram.*

an accuracy of 0.906, and after the interobserver agreement, they obtained higher k-coefficients than the B mode k −0.542 vs. *k* = 0.625, suggesting a possible method to assess vascular invasion. However, they used six different ultrasound settings, and this may hamper their results.

In a research setting, Mazzawi et al [42] published two cases where they tested EUS-E after radiofrequency ablation. Based on the fact that after ablation is difficult to distinguish residual from a recurrent tumor or fibrotic tissue, while the mass is only visible at CT/MR as decreased or unchanged by RFA, they USED EUS-E to figure out if there is any tumor tissue left. First, EUS-E was performed before the RFA procedure showing blue colored mass suggesting a hard tissue. Second, after RFA, the CT scan showed an increase in tumor diameter without any other characterization. While performing EUS-E, a mixture of blue and green areas was seen, suggesting central

#### **Figure 2.**

*Multimodal imaging of a solid pancreatic tumor, neuroendocrine tumor. A. EUS – Doppler imaging. B Contrastenhanced ultrasound imaging. C. EUS-E imaging with strain histogram.*

anechoic areas indicating necrosis and another hypoechoic region of the tumor mass. Thus, they suggest that since RFA could be performed sequentially, EUS-E might help in determining which region should be reassessed on future procedures.

The second technique available for EUS-E in a pancreatic setting, the shear-wave measurement, has only one study published so far on pancreatic masses with inconclusive results [43]. Shear wave velocity is measured, and faster propagation will be related to greater tissue elasticity. Ohno et al [43] compared EUS-SWM and EUS-E for 64 consecutive cases with solid pancreatic lesions and pointed out that the velocity of the shear wave when comparing pancreatic cancer to mass-forming pancreatitis was not statistically significant (p 0.5687), while the mean strain value was lower for pancreatic cancer 45.4 vs. 74.5; p 0.0007. They used an Arietta 850 (Hitachi Medical Systems Europe, Zug, Switzerland) device, which unfortunately may not visualize

*Endoscopic Ultrasound Elastography: New Advancement in Pancreatic Diseases DOI: http://dx.doi.org/10.5772/intechopen.103890*


#### **Table 1.**

*Available meta-analyses that focus in EUS-E strain assessment on pancreatic cancer.*

the propagation status of shear waves in the ROI. Moreover, as they mention, many artifacts may be encountered due to various reasons, such as tissue motion, nearby blood vessels, distortion, or precompression artifacts, as well as breathing, because the procedures are usually performed under conscious sedation. Thus, their conclusion was that this set of EUS-SWM is not feasible for pancreatic solid masses assessment and that EUS-E with strain ratios and histogram still remain the main adjuvant method to be considered.

#### **3.2 Chronic pancreatitis**

Currently, EUS-E is considered for pancreatic fibrosis assessment (as well as stiffness) by both strain and shear-wave elastography [44]. Even though transabdominal US-E has been reported at first [45, 46], EUS-E is the preferred method, due to its capability to better visualize the pancreas, regardless of the patient's body size. However, the technique still requires a highly experienced endoscopist (**Figure 3**).

Itoh et al [47] used quantitative analysis to diagnose pancreatic fibrosis using EUS-E of surgically resected specimens. They included 58 patients who underwent EUS-EG of the distal pancreas before performing a pancreatectomy of pancreatic tumor based on the concept that if a tumor is present in the pancreatic head, fibrosis might be present in the tail due to obstructive pancreatitis. When compared with histology, they maintained the same image as the EUS-E pattern by providing a median of 2.0 sections. They quantified four parameters of tissue elasticity (mean, standard deviation, skewness, and kurtosis) and obtained a significant correlation between all of them and the grade of pancreatic fibrosis. They concluded that with fibrosis progression, the skewness and kurtosis increased, whereas the standard deviation and mean decreased.

While this concept might be the ideal one, it is difficult to be introduced without comparing it to surgical specimens. On the other hand, EUS by itself is not standardized and has a low reproducibility in diagnosing chronic pancreatitis. Thus, by performing a histogram analysis, these drawbacks might be overcome. Kuwahara et al [48] published in 2017 their experience on using EUS on 96 patients. They performed EUS-E on the head of the pancreas and compared the mean values with no substantial difference (68.8 vs. 71.3); however, the interobserver reliability of chronic pancreatitis was substantial with a k value of 0.648 and a consistency ratio of 73%. They also mention that EUS characteristics with hyperechoic foci with shadowing and lobularity and honeycomb appearance, as well as the Rosemont Criteria, were correlated with

#### **Figure 3.**

*Multimodal imaging of chronic pancreatitis A. EUS – Doppler imaging. B. Contrast-enhanced ultrasound imaging. C. EUS-E imaging with strain histogram.*

EUS-E. In conclusion, they suggest that EUS-E is an objective method for the diagnosis of chronic pancreatitis and should be considered when performing EUS.

The elastography spectrum was enhanced with the shear wave devices implemented on EUS systems. Nonetheless, chronic pancreatitis benefited from this breakthrough, and recent studies have already been published. The first reports of EUS shear wave elastography [43, 49] compared the resulting values with the Rosemont classification and EUS criteria with positive results and suggested that shear wave values may assess the fibrotic changes, which occur in chronic pancreatitis. They obtained a high sensitivity of 100%, specificity 94%, and an AUROC (Area Under the Receiver Operating Characteristics) of 0.97, which highlights the EUS-SWM diagnostic capability and that also may surpass other imaging techniques. The exocrine and endocrine functions were also discussed if they might be correlated with

#### *Endoscopic Ultrasound Elastography: New Advancement in Pancreatic Diseases DOI: http://dx.doi.org/10.5772/intechopen.103890*

EUS-SWM since in chronic pancreatitis, they are both altered [50]. The EUS-SWM sensitivity, specificity, and AUROC obtained for diagnosing chronic pancreatitis were 83%, 100%, and 0.92. When discussing exocrine dysfunction with pancreatic function diagnostic tests, the AUROC was 0.78 with a cutoff value of 1.96, whereas for the endocrine dysfunction associated with diabetes mellitus, it was 0.63 with a cutoff value of 2.34.

EUS-E is a promising asset for chronic pancreatitis; however, there is a need for more studies since some limitations are still encountered. While the proper way to validate its use is represented by histology as a reference, in chronic pancreatitis this might be rather difficult, thus another setting should be proposed. Also, the use of shear waves seems to provide better data, as they estimate the stiffness of the tissue.

#### **3.3 Autoimmune pancreatitis**

Exploring new diagnostic paths, EUS-E might be a valid tool for AP assessment. The first cases were reported by Dietrich et al [51] after suspicion of chronic pancreatitis but had a final diagnosis of AIP after EUS. The stiffness that covers the entire pancreas is characteristic for AIP, which enables to easily distinguish AIP and pancreatic adenocarcinoma. Only one study tested EUS-E with strain ratio on AIP. The authors tried to show a positive relationship after steroid treatment in AIP by examining the patient before and 2 weeks after therapy. The patients showed a decrease in the strain ratio from (8.04 ± 2.29 to 3.44 ± 1.97 (*P* < 0.0001). This might promote EUS-E as a response to the therapy, which might be useful for clinicians.

Additionally, there is also a study published on SWE that compared patients with AIP with controls, yielding different values of share wave velocity (2.57 m/s vs. 1.89 m/s) (*P* = 0.0185). The study also tested the response to steroid therapy, and Vs significantly decreased from 3.32 to 2.46 m/s (*n* = 6) (P 0.0234), which highlights the technique's capability in AIP [49, 51, 52].
