Early chronic pancreatitis: a challenge not so far to be met

One of the most complex topics in pancreatology is represented by early chronic pancreatitis (ECP), for which a clear definition is still lacking. An attempt to give a definition was carried out by the consensus ¹ published in 2019, in which ECP is defined as the initial stage manifestation of an inflammatory chronic process of the pancreas. This entity represents a challenge for pancreatologists because it is the stage of the disease with a potential reversibility of morphological and functional alterations of the pancreas but, at the same time, it is extremely difficult to diagnose by imaging techniques. Indeed, abdominal computed tomography (CT) scan and magnetic resonance imaging (MRI) are not able to identify minimal changes typical of ECP in pancreatic parenchyma. Endoscopic ultrasound (EUS) has a higher sensitivity with respect to other methods and has also well-defined criteria to stratify the severity of the disease according to structural changes, calcifications and fibrosis.^2,3

Nevertheless, guidelines underline how the diagnosis of ECP is not only morphological, but also based on other factors such as personal history or functional alterations. Therefore, EUS represents the exam that can potentially give more information for the diagnosis of ECP because it permits the use of many ancillary techniques simultaneously.

For these reasons, the article by Dominguez-Munoz and colleagues ⁴ published in the August issue of the journal is of utmost interest: in that prospective, cross-sectional, observational study 53 patients with clinically suspected ECP were included and a multimodal EUS-based approach using four parameters (EUS criteria of CP, quantitative pancreatic elastography, endoscopic pancreatic function test (ePFT) and compliance of the main pancreatic duct after secretin stimulation) was adopted. This approach permits the evaluation in the same exam of more ECP features at once: morphological alterations with B-mode EUS, the parenchymal fibrosis through the stiffness measured by endoscopic ultrasound-elastography (EUS-EG), secretory functionality of the pancreas with ePFT and the compliance of the ducts after secretin administration. The paper, compared with what is reported in the literature up to now, has the advantage of focusing only on those patients with a suspected ECP but who do not have morphological alterations typical of defined CP. The results shown are pretty encouraging and suggest the use of EUS as the most adequate technique to diagnose ECP. In fact, the study showed that in all patients at least three of four parameters of the multimodal approach were altered. More specifically, in all patients there were minor morphological alterations, such as hyperechoic foci and strands, and an increased strain ratio (SR) at EUS-EG, all signs of an increased quota of fibrous tissue. ePFT and compliance of the pancreatic duct were also frequently altered, in 81.1% and 77.3% of cases, respectively. Hence, the study demonstrated convincingly that EUS could be fundamental in the diagnosis of ECP, underlining in particular the possible role of EUS-EG. EUS-EG has for years been introduced in clinical practice during endosonographic exams ⁵ because it is safe, easy to apply and quick, but the sensitivity and specificity were very variable. Indeed, there is ongoing debate regarding the most accurate elastographic technique. In the present study by Dominguez-Munoz and colleagues ⁴ it was the SR technique that gives a ‘relative’ stiffness measure. In SR the strain of a region of interest (ROI) is compared with the strain of a region in normal surrounding reference tissue. The drawback of SR is that it depends from which comparator the ROI is chosen. ⁶ In fact, SR was developed for the breast to compare pathological lesions with healthy surrounding tissue in the very same gland. In pancreatic diseases this is more difficult because there is frequently no normal tissue to be compared close to the disease, and the choice of a different tissue could falsify the results of SR. In chronic diseases such as CP or chronic hepatitis, in which great parenchymal involvement can be observed, a more objective technique, to date, could probably be the strain histogram (SH), that gives a semiquantitative calculation of stiffness and of its distribution. ⁷ SH is more objective and accurate because it evaluates only the ROI of the disease, not considering the surrounding tissue. In transabdominal ultrasonography share wave elastography is also used, which allows us to obtain an absolute value of stiffness. During recent years some promising reports about the application of this technique in EUS have been published. ⁸ Finally, in our opinion, it will be very interesting to see how the application of artificial intelligence (AI) in EUS could further improve the diagnostic accuracy of this method. Some preliminary studies, also on CP, have already been published and they have shown that the application of AI in elastography can differentiate very well between mass-forming CP and neoplasia. ⁹

EUS-EG is undoubtedly a technique that can really help to reach a diagnosis of CO and, most of all, ECP. To date few papers have been published on the diagnostic capacity of SR (fundamentally used in Spain ⁴ and Japan) ¹⁰ or SH. In the future comparative prospective studies about these two techniques could suggest which one should be used in the diagnosis of CP, especially ECP.