Endoscopic ultrasound elastography in diagnosing chronic pancreatitis: has the strain ratio found its region of interest?

Endoscopic ultrasonography (EUS) imaging of chronic pancreatitis was first reported in 1986 [1] [2] and a recent systematic review retrieved 51 articles published in the past decade (January 2001 – January 2010) compared with 13 articles in the previous 20 years (1980 – 2000) [3]. Despite this abundant literature, the role of EUS in the diagnosis of chronic pancreatitis is still far from being well established. Chronic pancreatitis has traditionally been regarded as difficult terrain for EUS because it is difficult to diagnose per se, particularly in its early stages, and also because it induces artifacts that hamper the detection of pancreatic neoplasms. Moreover, changes seen on EUS might be early ones and do not necessarily reflect function; hence, there has always been some debate over EUS findings and their clinical relevance, with the potential for EUS to over-diagnose chronic pancreatitis.

Several studies have looked at standardization and inter/intraobserver agreement of EUS criteria (parenchymal and ductal) using correlations with histology as the reference standard [4] [5] [6] [7] [8]. In other studies, EUS performance in diagnosing chronic pancreatitis has been evaluated compared with different diagnostic modalities such as endoscopic retrograde pancreatography [9], magnetic resonance pancreatography [10], pancreatic function testing [11], fecal elastase 1 [12], and IL-8 in pancreatic juice [13]. Overall, whereas EUS was accurate for the detection of severe chronic pancreatitis (normally > 5 criteria are required to match this diagnosis), it was still regarded as being inaccurate for the detection of mild and moderate chronic pancreatitis ( ≤ 5 criteria) [14].

Several techniques of EUS image enhancement have been introduced in recent years to increase the diagnostic yield of EUS by providing objective reference patterns that are independent from the observers’ judgment. These include: (a) EUS – elastography; (b) contrast-enhanced EUS; and (c) digital image analysis [15] [16] [17].

In this issue of Endoscopy, Iglesias-Garcia et al. [18] from Spain published their experience with EUS – elastography compared with standard EUS for the detection of chronic pancreatitis. Indications for EUS included epigastric pain and follow-up of previously diagnosed chronic pancreatitis. Parenchymal and ductal criteria of chronic pancreatitis were first evaluated by standard EUS. Chronic pancreatitis was ruled in when ≥ 5 criteria were present and it was ruled out when ≤ 2 criteria were present. Cases with 3 – 4 criteria were considered indeterminate and an additional diagnostic method was performed (secretin-stimulated magnetic resonance cholangiopancreatography and a contrast-enhanced pancreas magnetic resonance with intravenous gadolinium) to either confirm or exclude chronic pancreatitis. As a result, 92 patients were considered to have chronic pancreatitis and 99 had a normal pancreas (comparison group). EUS – elastography was performed in both groups with a radial echoendoscope taking measurements of the strain ratio in the head, body, and tail of the pancreas. It was found that the strain ratio values were significantly higher in chronic pancreatitis than in normal pancreas. Measurements were consistent throughout the three regions of the gland in both groups of patients. Moreover, there was a significant correlation between the strain ratio value and the number of EUS criteria; in other words, the higher the strain ratio value the more severe was the disease. When a strain ratio cut-off value of 2.25 was adopted, overall accuracy of EUS – elastography reached 91 %.

Elastography uses ultrasound to observe tissue shear deformation and is dependent on tissue elasticity [19]. The rationale for using EUS – elastography in chronic pancreatitis lies in detecting the increased degree of fibrosis in diseased pancreas compared with normal pancreas. Several studies have utilized EUS – elastography for differential diagnosis of focal pancreatitis and pancreatic cancer, with variable results according to the technique used (either qualitative or semi-quantitative).

The qualitative technique is quite straightforward as it simply evaluates the color of the tissue displayed by the region under investigation. The different colors reflect the differences in hardness between the tissues, where soft normal tissue appears red/green and hard neoplastic tissue appears blue [20].

The semi-quantitative technique involves the measurement of the strain ratio value. Basically, the tissue stiffness is measured inside the lesion (region of interest A) and outside the lesion in a region representing normal tissue (region of interest B). The strain ratio value is the quotient B/A, a number which appears to be more reproducible than the visual appraisal of the predominant color [21].

Although better accuracy has been found with the semi-quantitative compared with the qualitative technique in the differential diagnosis of focal pancreatitis and pancreatic cancer, the strain ratio is not fully standardized and some authors have reported unsatisfactory results [22].

The use of EUS – elastography rather than standard EUS for detecting chronic pancreatitis is original. In detail, the authors aimed at increasing the diagnostic yield of EUS, particularly in those cases that are indeterminate for chronic pancreatitis using current parenchymal and ductal criteria. By using the qualitative technique first, Iglesias-Garcia et al. [18] reported that chronic pancreatitis appeared heterogeneously green compared with normal pancreas, which was homogeneously green. Very scant data are available in the literature for comparison. Janssen et al. [23] described 20 patients with chronic pancreatitis who showed a prevalent blue heterogeneous pattern. Unlike the Spanish study, a linear echoendoscope was used to perform EUS – elastography in a smaller cohort of patients with various pancreatic diseases. A blue pattern was also reported by Dietrich et al. [24] in a case series of autoimmune pancreatitis. All five patients presented with a characteristic stiff (blue) elastography pattern not only of the mass-forming autoimmune pancreatitis but also of the surrounding pancreatic parenchyma, which was not found in patients with ductal adenocarcinoma and healthy controls. Although the Iglesias-Garcia study reported that elastography patterns were consistent in the head, body, and tail of the pancreas, it did not provide data on how many cases with focal chronic pancreatitis rather than diffuse disease were included in the study.

The use of semi-quantitative EUS – elastography in differentiating chronic pancreatitis from normal pancreas is innovative and may prove to be a more reliable use of the strain ratio than the differential diagnosis between chronic pancreatitis and cancer. In the Spanish study [18], 22 out of 92 patients with chronic pancreatitis did not reach the sufficient number of diagnostic criteria and thus were diagnosed only by means of magnetic resonance. Interestingly, EUS – elastography was able to correctly detect chronic pancreatitis in 17 /22 of them by using a strain ratio cut-off value of 2.25. In this respect, EUS – elastography allowed an 18 % incremental diagnostic yield compared with standard EUS. Moreover, the results of the Spanish study are appealing because the technique is easy, quick, and inexpensive (no injection of contrast agent is required to perform EUS – elastography).

Nevertheless, a few technical issues remain. First, it is generally recommended to avoid size inequality between the pancreatic and the reference area when using the strain ratio technique [25]. However, in the Spanish study [18], region A was as large as the pancreatic head/body/tail, whereas region B was as small as a minute circle on the gastrointestinal wall, which represents a good tissue for comparison but is very unequal in size. As a result, size inequality between the two regions of interest might have resulted in impaired measurements. Second, interposition of cystic lesions and dilated ducts between the target parenchyma and the transducer may also impair strain ratio assessment. We presume that several patients in the Spanish study presented with cysts and dilated ducts as they are typical diagnostic criteria for chronic pancreatitis. Unfortunately, data about these features were not provided. Third, other technical issues regarding position of the target relative to the transducer, degree of transducer compression, and angulation of the probe may interfere with accuracy and reproducibility of EUS – elastography. Further technical evaluation of this promising method is needed before it becomes an established adjunct to EUS for the diagnosis of chronic pancreatitis, which is a difficult task for any imaging technique.

Finally, as EUS – elastography appeared to correlate with the severity of the disease in the Spanish study [18] (strain ratio values becoming higher as the number of diagnostic criteria for chronic pancreatitis increased), we speculate that EUS – elastography might represent an accurate tool not only for diagnosis but also for follow-up of chronic pancreatitis. In fact, withdrawal of the causative agent of chronic pancreatitis (mainly alcohol) is known to arrest the worsening of fibrosis. In this respect, two identical measurements of strain ratio over time in the same patient may indicate a stationary disease whereas an increase in the strain ratio may represent worsening disease that requires possible therapeutic intervention. Additionally, this application of EUS – elastography could potentially be used for evaluation and follow-up of diseases such as autoimmune pancreatitis.

• References

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