Contrast enhancement during endosonography to diagnose autoimmune pancreatitis

We read with interest the article by Hocke et al. about the use of contrast-enhanced endosonography (CE-EUS) in the diagnosis of autoimmune pancreatitis (AIP) [1]. In this study, the authors examined 10 patients with AIP and five patients with pancreatic cancer and compared CE-EUS findings in both groups. Final diagnosis was achieved by either histology or cytology with immunostaining of immunoglobulin (Ig) G4 antibody. The authors reported that CE-EUS revealed net-like hypervascularization in 90 % of the cases with AIP and hypovascular lesions in cases of pancreatic carcinoma.

CE-EUS has been suggested to provide additional information, above and beyond that which is obtained from conventional EUS, in the differentiation of inflammatory tumor-like masses and pancreatic adenocarcinoma. The sensitivity and specificity of the discrimination between benign and malignant pancreatic mass lesions has been reported to increase by approximately 10 % when using CE-EUS compared with conventional EUS [2]. Focal AIP, which is regarded as part of a spectrum of a diffuse variant, usually presents as a swelling or mass formation in any part of the pancreas. Focal AIP is not seen as commonly as diffuse AIP, but most focal AIP patients undergo surgical treatment due to provisional diagnosis of pancreatic carcinoma. The Hocke study seemed to aim to differentiate tumor-forming AIP from the real tumor or pancreatic carcinoma by using CE-EUS. However, as far as we understand from the text, not all cases of AIP included in this study had mass or focal lesion formation; at least one of them had a normal vessel pattern similar to that which is seen in healthy controls. This case possibly reflects the diffuse variant of AIP with characteristics of minimal-change chronic pancreatitis. The authors also described a net-like hypervascularization pattern in most of their patients with AIP. However, in a previous study using Sonazoid as a contrast agent during EUS examination for AIP, the isovascular pattern was noticed in 75 % of cases, while hypoenhancement was described in 25 % of the study group [3]. It is unlikely or questionable that the different contrast agents result in different enhancement patterns in cases of AIP. However, we know that the pattern of vascularization depends on the amount of necrosis, inflammation, and fibrosis [4]. The level of inflammation and fibrosis in the pancreatic tissue can be reflected in different enhancement patterns in cases with AIP and pancreatic carcinoma.

Furthermore, the authors emphasized the necessity of histologic or cytologic confirmation of AIP. We believe that it is controversial to perform routine pancreatic sampling in a patient with focal mass formation in the pancreas if there is strong evidence against the existence of malignancy, such as elevated IgG4, lower levels of CA 19 – 9, or non-dilated main pancreatic duct on imaging methods. We also know that diffuse delayed homogeneous enhancement of pancreatic tissue on dynamic computed tomography is important evidence for absence of malignancy in a case with focal AIP [5]. Steroid challenge in such cases, particularly where IgG4 subclasses are elevated, might be warranted and could avoid more invasive testing.

Finally, as the authors indicated in the paper, we believe that the learning curve is very important in order to achieve optimal imaging and evaluation during CE-EUS examination. However, CE-EUS needs a higher resolution Doppler ultrasonography device, which is more expensive than the standard one. In addition, although CE-EUS might be a useful aid in identifying the tumor vasculature and studying microcirculation in pancreatic diseases, the second-generation contrast agents are not cheap (70 % per 5-mL ampoule) and are difficult to obtain in many countries including our own. While more data are needed and comparative trials are being awaited, the cost-effectiveness of contrast enhancement during EUS examination compared with standard endosonography has not been well studied.

References

• 1 Hocke M, Ignee A, Dietrich C F. Contrast-enhanced endoscopic ultrasound in the diagnosis of autoimmune pancreatitis.  Endoscopy. 2011;  43 163-165
• 2 Hocke M, Schulze E, Gottschalk P et al. Contrast enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer.  World J Gastroenterol. 2006;  12 246-250
• 3 Figueiredo F A, Giovannini M, Bories E et al. Endoscopic ultrasonography (EUS) strain ratio (SR-EUS) vs. contrast-enhanced EUS (CE-EUS) for the diagnosis of focal pancreatic lesions.  Gastrointest Endosc. 2009;  69 AB129
• 4 Seicean A, Badea R, Stan-Iuga R et al. The added value of real-time harmonics contrast-enhanced endoscopic ultrasonography for the characterization of pancreatic diseases in routine practice.  J Gastrointestin Liver Dis. 2010;  19 99-104
• 5 Wakabayashi T, Kawaura Y, Satomura Y et al. Clinical and imaging features of autoimmune pancreatitis with focal pancreatic swelling or mass formation: comparison with so-called tumor forming pancreatitis and pancreatic carcinoma.  Am J Gastroenterol. 2003;  98 2679-2687