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Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia
European Journal of Radiology 75 (2010) e38–e44
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia Francescamaria Donati a,∗ , Piero Boraschi a , Roberto Gigoni a , Simonetta Salemi a , Lorenzo Faggioni b , Cristina Bertucci b , Claudia Cecchi b , Carlo Bartolozzi b , Fabio Falaschi a a b
2nd Department of Radiology, Pisa University-Hospital, Via Paradisa 2, I-56124 Pisa, Italy Diagnostic and Interventional Radiology, University of Pisa, Via Rome 67, I-56126 Pisa, Italy
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Article history: Received 5 May 2009 Received in revised form 8 November 2009 Accepted 11 November 2009 Keywords: MR cholangio-pancreatography Secretin Pancreatic ducts MR Pancreatic hyperenzymemia
a b s t r a c t Purpose: To assess the diagnostic value of secretin-stimulated MRCP (SS-MRCP) compared with conventional MRCP in asymptomatic patients with mild elevations of pancreatic enzymes. Materials and methods: Eighty asymptomatic patients with pancreatic hyperenzymemia underwent MR imaging at 1.5 T-device (Signa EXCITE, GE Healthcare). After the acquisition of axial T1w,T2w sequences, and conventional MRCP, SS-MRCP was performed using a single-slice coronal breath-hold, thick-slab, SSFSE T2w sequence, repeated every 30 s up to 15 min following intravenous injection of secretin (Secrelux® , Sanochemia). Results: On the basis of the standards of reference, our final diagnoses were: negative findings (n = 23), pancreas divisum (n = 22), mild chronic pancreatitis (n = 14), inflammatory ampullary stenosis (n = 3), juxtapapillary duodenal diverticulum (n = 1), small cystic lesions (<1 cm) (n = 22; 5/22 cases associated with pancreas divisum). The image quality of SS-MRCP was significantly higher than that of conventional MRCP (p < 0.0001). Standards of reference did not differ significantly from of SS-MRCP findings (p = 0.5), while was statistically different from those of conventional MRCP (p < 0.0001). A significant difference was found between conventional MRCP and SS-MRCP findings (p < 0.0001). Conclusion: In asymptomatic patients with non-specific pancreatic hyperenzymemia SS-MRCP may represent the best non-invasive diagnostic technique, since it gives morphological and functional information. © 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction An increase in serum levels of pancreatic enzymes is a well-known manifestation of pancreatic disease, especially acute pancreatitis. However, mild elevations are considered non-specific; they have been reported to occur in a variety of pancreatic and extrapancreatic metabolic or structural derangements, such as anatomic variants of the pancreatic duct, recurrent chronic pancreatitis, chronic liver disease, inflammatory bowel disease and so on [1–3]. In addition to this pathological type of hyperenzymemia several non-pathological forms have also been identified, included in a new syndrome named “benign pancreatic hyperenzymemia” [4]. MR cholangio-pancreatography (MRCP) is a non-invasive imaging technique that accurately depicts the morphologic features of the pancreatic ducts. In several studies [5–10], MRCP demonstrates a good correlation with endoscopic retrograde
∗ Corresponding author. Tel.: +39 050 996782; fax: +39 1782211474. E-mail address: [email protected] (F. Donati). 0720-048X/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2009.11.008
cholangio-pancreatography (ERCP) in the evaluation of disease and anatomic variants of the pancreatic ductal system; however, in physiologic conditions the pancreatic ducts, particularly sides branches, are not always depicted [6]. More recently, however, several authors [11–17] have demonstrated that the injection of secretin improves MRCP depiction of the pancreatic ducts, detection and characterization of pancreatic disorders and may allow estimation of exocrine pancreatic reserve. Our study was aimed to assess the diagnostic value of secretinstimulated MRCP (SS-MRCP) compared with conventional MRCP in asymptomatic patients with mild elevations of pancreatic enzymes. 2. Material and methods 2.1. Patients Our study was performed in accordance with the recommendations of our institutional review board and written informed consent was obtained after explanation of the complete examination procedure.
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Between September 2004 and September 2007, 80 asymptomatic patients (38 men and 42 women; mean age, 49.94 ± 8.93 years; age range, 31–68 years) with persistent (for at least 6 months) non-specific serum hyperamylasemia and hyperlipasemia, defined as elevations less than to three times the normal level (normal values are 30–110 U/L for amylase and 13–300 U/L for lipase), were prospectively included in our study group. All patients underwent MR study before and after stimulation with secretin. The following standards of reference were available: duodenal endoscopy with biopsy of the major papilla; intra-operative findings; multi-rows detector CT (MDCT); and clinical (monitoring of pancreatic enzyme levels and symptoms, every 3 months) and imaging (MDCT, at 6 and 18 months, and SS-MRCP at 12 and 24 months) follow-up for at least 12 months. 2.2. MR imaging The MR examinations were performed with superconductive systems operating at 1.5 T (Signa EXCITE, GE Healthcare) with high performance gradients. The phased-array coil was used for both excitation and signal reception. Ten minutes before MRI, a super-paramagnetic suspension (Lumirem® 100 mL, Guerbet) was orally administered to suppress the signal intensity of overlapping fluid-containing organs. Scopolamine methyl-bromide (Buscopan® 20 mg/mL, Boehringer Ingelheim) was intramuscularly administered immediately before starting the examination in order to avoid peristaltic artefacts. The imaging protocol began with axial, breath-hold, with and without fat-suppressed spoiled gradient-echo (SPGR) T1-weighted images (repetition time, 110–130 ms; echo time, minimum full, with effective 2.1–2.3 ms; flip angle, 80◦ ; section thickness, 5 mm; interslice gap, 0.5 mm; matrix size, 256 × 192 pixels; signal averaged, 1; acquisition time, 28–32 s); axial, respiratory-triggered, fat-suppressed, fast spin-echo (FSE) T2-weighted sequence (repetition time automatically adapted to the patient’s breathing pattern, 6000–18000 ms; echo time, 95.5 ms; echo train length, 16; section thickness, 5 mm; interslice gap, 0.5 mm; signals averaged, 3–4; acquisition time, 3–4 min) and/or axial, breath-hold, single-shot fast spin-echo (SSFSE) T2-weighted sequence (repetition time, minimum; echo time, 80 ms; section thickness, 5 mm; interslice gap, 0.5 mm; signal averaged, 0.5–0.6; acquisition time, 18 24 s). Conventional MRCP was performed by means of coronal respiratory-triggered, three-dimensional fast spin-echo (3D FRFSE), heavily T2-weighted sequence (repetition time automatically adapted to the patient’s breathing pattern, 3000–15000 ms; effective echo time, 622 ms; section thickness, 2.4 mm; interslice gap, −1.2 mm; field of view, 35–45 cm; matrix size, 256 × 128 pixels; signal averaged, 2; acquisition time, 3–4 min), and coronal breath-hold, thick-slab, single-shot fast spin-echo (SSFSE) T2w sequence (effective echo time, 1052 ms; thickness, 40–60 mm; field of view, 35–45 cm; matrix size, 256 × 256 pixels; 0.5 signal averaged; acquisition time, 1–2 s for every image). Subsequently, SS-MRCP was performed using a coronal breathhold, thick-slab, SSFSE T2w sequence, with the same parameters reported above, covering the pancreas and adjacent small bowel. After the acquisition of the first image, secretin (Secrelux® , Sanochemia; 1 cU/kg body/weight) was injected intravenously in order to stimulate the pancreas to produce exocrine secretion and single-slice image acquisition was repeated every 30 s up to 15 min. 2.3. Image analysis All MR images were analyzed in consensus by two radiologists (P.B. and R.G.), with more than 15 years experience on biliary and pancreatic MR imaging, who were blinded to patient identification and all results of the standard references or the final diagnoses.
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Image quality before and after secretin stimulation was classified semi-quantitatively using a five-points score: 1, no delineation; 2, poor; 3, sufficient; 4, good; 5, excellent. The visualization of the pancreatic ductal system was classified separately for the main pancreatic duct, and for accessory and side branches. A functional evaluation of the exocrine pancreatic reserve was also performed by a semi-quantitative image analysis of the duodenal filling on the basis of pancreatic secretion after secretin stimulation. The pancreatic fluid outflow was visually analyzed on the image time series by the two observers. The duodenal filling volume was graded according to the scale (0–3) derived by Matos et al. [6]: grade 0, no fluid observed; grade 1, filling limited into the duodenal bulb; grade 2, filling duodenum up to the genu inferius; grade 3, filling duodenum beyond the genu inferius. The exocrine function was considered to be reduced when the duodenal filling volume grade was less than 3. Diagnostic image analysis included the evaluation of the presence of: focal pancreatic lesions and their relationship to the pancreatic ductal system; anatomic variants of the pancreatic duct; abnormal side branches; morphologic changes of the main pancreatic duct; and hepato-biliary abnormalities. Chronic pancreatitis was diagnosed on the basis of the Cambridge classification if at least three abnormal side branches or main pancreatic ductal irregularities were present [10]. MR images before and after secretin stimulation were evaluated on a dedicated workstation (Advantage Windows 4.4; GE Healthcare) separately and in a randomized fashion. These results were correlated with the final diagnoses on the basis of the previously mentioned standards of reference. 2.4. Statistical analysis The distribution of the qualitative variables was expressed as the relative frequency of the various modalities under observation. The distribution of the quantitative variables was expressed as the mean, standard deviation, minimum, maximum and number of observations. The comparison between image quality scores obtained before and after secretin stimulation was evaluated by means of two-tailed Wilcoxon rank test. The proportion of agreement among conventional MRCP, SS-MRCP and standards of reference was assessed by using McNemar test. Statistical analysis was carried out through the VassarStats website (http://faculty.vassar.edu/lowry/VassarStats.html). A threshold of p < 0.05 was considered for statistical significance. 3. Results On the basis of the standards of reference, our final diagnoses were: 23 negative findings; 22 cases of pancreas divisum; 14 cases of mild chronic pancreatitis; 3 cases of inflammatory ampullary stenosis; one case of juxtapapillary duodenal diverticulum; and 22 cases of microcysts (in 5 patients associated with pancreas divisum) (Table 1). All 80 MR studies were considered diagnostic by the reviewers. All patients well tolerated the examination, and no side effect was reported after secretin administration. Image quality findings are summarized in Table 2. The image quality of SS-MRCP was significantly higher than that of conventional MRCP, both overall (p < 0.0001) and as regards depiction of accessory ducts and/or side branches (p < 0.0001). Diagnoses before and after secretin stimulation are reported in Table 3. Conventional MRCP showed pancreatic abnormalities in 40 out of 80 (50%) patients, while after secretin stimulation pancreatic abnormalities were observed in 55 out of 80 (68.7%) patients. The primary diagnosis was changed after secretin stimulation in 22 out of 80 (27.5%) patients.
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F. Donati et al. / European Journal of Radiology 75 (2010) e38–e44 Table 3 Imaging findings on conventional and SS-MRCP.
Table 1 Final diagnoses on the basis of the standards of reference. No. of patients
Standards of reference
Pancreas divisum Mild chronic pancreatitis
22 14
Ampullary stenosis Juxtapapillary duodenal diverticulum Small cysts (<1 cm)
3 1 22
Negative findings
23
Imaging follow-up MDCT; clinical and imaging follow-up Endoscopic biopsy Surgery MDCT; clinical and imaging follow-up MDCT; clinical and imaging follow-up
Final diagnosis
Diagnosis
A pancreas divisum was found in 12 patients before and in 22 patients after secretin administration. Both dorsal and ventral pancreatic ducts, with predominant drainage through the minor papilla, were recognized in all 22 cases of pancreas divisum after secretin injection (Fig. 1). Morphologic changes compatible with mild chronic pancreatitis, characterized by the presence of at least three abnormal side branches in the head and tail, were identified in two cases on conventional MRCP, and in 12 cases on SS-MRCP; secretin stimulation improved visualization of both main pancreatic duct and the side branches (from two to 12 cases) particularly at the level of the tail (Fig. 2), with a sensitivity of 85.7% in the detection of chronic pancreatitis. However, SS-MRCP did not identify two cases of mild chronic pancreatitis (two false negative results), diagnosed at 6 and 12 months imaging follow-up, showing the first case ductal irregularity and parenchymal micro-calcifications at MDCT, and the second one ductal irregularities in the head and body and dilated side braches in the tail at SS-MRCP. In three cases, inflammatory ampullary stenosis was diagnosed on both the techniques, showing the dilation of main pancreatic duct and common bile duct; in these cases after secretin stimulation the calibre of the main pancreatic duct increased and remained enlarged for all 15 min (Fig. 3). MR images showed also one case of juxtapapillary duodenal diverticulum, that determined dislocation of adjacent Wirsung; furthermore, SS-MRCP well demonstrated the filling of diverticulum by pancreatic secretion (Fig. 4). Small non-specific cystic lesions (<1 cm) were also seen in 22 patients (associated with pancreas divisum in 5 out of 22 cases) on both types of MRCP; however, conventional MRCP mistakenly diagnosed two cases of alpha loop in the pancreatic duct as small pancreatic cyst (two false positive results). After secretin injection a normal duodenal filling, corresponding to grade 3, was observed in 74 patients. Pancreatic fluid outflow appeared reduced (grade 1 in two cases and grade 2 in one) in the three patients with inflammatory ampullary stenosis. Grade 2 of duodenal filling was also appreciable in three patients with mild chronic pancreatitis, suggesting reduced exocrine pancreatic reserve; in two out of these three cases SS-MRCP also showed “acinar filling”, demonstrating progressive hydrographic enhancement of the pancreatic parenchyma (Fig. 5). Standards of reference did not differ significantly from of SSMRCP findings (p = 0.5), while was statistically different from those derived from conventional MRCP (p < 0.0001). Furthermore, a sig-
Conventional MRCP
Pancreas divisum (n = 22) Mild chronic pancreatitis (n = 14) Ampullary stenosis (n = 3) Juxtapapillary duodenal diverticulum (n = 1) Small cysts (<1 cm) (n = 22)
*
SS-MRCP 22 12* 3 1 22
12 2* 3 1 24**
Note: * false negative; ** false positive.
nificant difference was also found out between conventional MRCP and SS-MRCP findings (p < 0.0001). 4. Discussion The causes of increased levels of serum pancreatic enzymes may be related to pancreatic disease. In the absence of pathologies of the pancreas, the possible cause of an increased enzyme release from the pancreas is generally a mild obstruction of the pancreatic ductal system, that alters the normal exocytosis process in the acinar cells [3]. Because of the large spreading of asymptomatic patients with increased pancreatic enzymes levels and without evident reasons for biochemical alteration, the possible causes should be carefully investigated with instrumental examination to exclude pancreatic disorders in clinical practice. MRCP has evolved as an accurate imaging technique for the non-invasive evaluation of the pancreato-biliary tract [5–10,18]. The diagnostic accuracy of MRCP is comparable to that of ERCP in the evaluation of disease and anatomic variants of the pancreatic ducts; in physiologic conditions, however, the pancreatic ducts, particularly sides branches, are not always depicted [6,7]. Several authors [11–17] reported that MRCP after secretin stimulation shows a significant improvement of visualization of the main pancreatic duct and the Santorini duct in all patients having a normal exocrine pancreatic function. Secretin administration stimulates fluid and bicarbonate secretion by the exocrine pancreas and simultaneously increases tonus of the sphincter of Oddi, inducing a transitory dilation of the main pancreatic duct, which improves visualization. In addition, the degree of duodenal filling resulting from the drainage of pancreatic fluid can be evaluated as an indirect measure of exocrine pancreatic function [16]. Therefore, various reports [11,13,15] have demonstrated that SS-MRCP is useful for the morphologic and functional evaluation of the pancreatic duct. To our knowledge, few reports have focused on the evaluation of asymptomatic patients with mild pancreatic hyperenzymemia and for this reason we aimed to investigate the spectrum of SS-MRCP findings in this group of patients. On the first report focused on this matter from an imaging perspective Mortelé et al. [19] studied these asymptomatic biochemical alterations using conventional MRCP, without secretin stimulation. Their results suggested that 31 out of 54 patients (57%) presented pancreatic abnormalities on MRCP. More recently, Testoni et al. [20] compared 25 asymptomatic patients with pancreatic hyperenzymemia with 28 normal controls, all studied with MRCP after secretin injection, and demon-
Table 2 Image quality before and after secretin stimulation.
Main duct C-MRCP Main duct SS-MRCP Accessory/side branches C-MRCP Accessory/side branches SS-MRCP
Grade 1 (n=)
Grade 2 (n=)
Grade 3 (n=)
Grade 4 (n=)
Grade 5 (n=)
9 – 62 43
53 – 11 2
17 – 6 –
1 27 1 17
– 53 – 18
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Fig. 1. (a–c) 49-year-old man with recurrent (since 15 months) asymptomatic increase of pancreatic enzyme levels. (a) MRCP obtained using coronal breath-hold, thick-slab, SSFSE T2w sequence MRCP reveals only the dorsal pancreatic duct before secretin administration. (b) MRCP obtained 3 min after secretin injection demonstrates both the ventral (arrow) and the dorsal pancreatic duct, without connection between them and prompt outflow of pancreatic secretion via the minor papilla, corresponding to pancreas divisum with dominant dorsal duct. (c) MRCP obtained 15 min after secretin injection shows normal duodenal filling beyond the genu inferius.
strated abnormal pancreatic morphological findings in 13/25 patients (52%) and 1/28 controls (3.6%) (p < 0.001). These authors concluded that MRCP after secretin administration is to be recommended, instead of MRCP alone, in the diagnostic work-up of asymptomatic patients with pancreatic hyperenzymemia.
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Fig. 2. (a–c) 52-year-old woman with persistent (for at least 9 months) non-specific serum hyperamylasemia and hyperlipasemia. (a) MRCP obtained before secretin injection shows a normal main pancreatic duct. (b) Three minutes after secretin stimulation, MRCP reveals side branches dilation, particularly at the level of the head and tail diagnosed as mild chronic pancreatitis. (c) MRCP obtained 15 min after secretin injection demonstrates normal duodenal filling beyond the genu inferius, interpreted as preserved pancreatic exocrine reserve.
According to their results, in our study, conventional MRCP showed abnormalities of the pancreas in 40 out of 80 (50%) patients; while SS-MRCP identified positive results in 55 out of 80 (68.7%) patients, with a significant difference between conventional MRCP and SS-MRCP findings (p < 0.0001). Furthermore, primary diagnosis was changed in 22 out of 80 (27.5%) patients. The most common pancreatic finding identified in our series was pancreas divisum, observed in 22 patients (27.5%), while the prevalence in the normal population is of 5–14% [19]. Before secretin injection ventral duct was not seen in 10 cases, while after secretin
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Fig. 3. (a–c) 69-year-old man with asymptomatic recurrent increase (since 12 months) of pancreatic enzyme levels. (a) MRCP obtained before secretin administration reveals distal common bile duct stenosis, with consequent dilatation of extra-hepatic bile ducts. Head portion of pancreatic duct is only slightly dilated. (b) MRCP obtained 3 min after secretin injection shows increasing diameter of pancreatic duct. Compared with A, there is improved visualization of pancreatic ductal irregularities and of duct narrowing in head portion (arrow). (c) MRCP obtained 15 min after secretin injection demonstrates duodenal filling up to genu inferius (grade 2), interpreted as reduced exocrine pancreatic reserve. Endoscopic evaluation with papillary biopsy diagnosed inflammatory ampullary stenosis.
stimulation it was recognized in all cases; predominant drainage through the minor papilla was always demonstrated. Postulated that, in pancreas divisum, pancreatic hyperenzymes may result from mild obstruction of outflow of pancreatic secretion through the minor papilla [19–22], SS-MRCP can be an important physiologic challenge to assess the relevance of any degree of papillary stenosis [16]. Morphologic changes compatible with mild chronic pancreatitis were demonstrated in 12 patients on SS-MRCP. Several authors
Fig. 4. (a–c) 57-year-old woman with juxtapapillary duodenal diverticulum and recurrent (since 18 months) non-specific increase of pancreatic enzyme levels. (a) MRCP obtained before secretin administration shows the main pancreatic duct with abnormal and irregular course and demonstrates a voluminous kinking at the level of the head. (b) MRCP obtained 10 min after secretin injection visualizes increasing diameter of pancreatic duct and fluid-filled juxta-duodenal lumen (arrow). (c) Coronal-oblique MIP from 3D-SSFSE repeated 20 min after secretin injection demonstrates fluid-filled juxtapapillary duodenal diverticulum (arrow). The communication between main pancreatic duct and diverticulum was confirmed at surgery.
[6,12,15,17] reported the usefulness of SS-MRCP in the diagnosis of chronic pancreatitis. Hellerhoff et al. [16] reported that the overall sensitivity of MRCP in the detection of chronic pancreatitis increased from 77% to 89% after secretin injection and that the benefit of secretin administration is even greater in the case of
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Fig. 5. (a and b) 62-year-old man with asymptomatic persistent (for at least 6 months) increase of pancreatic enzyme levels. (a) Secretin-stimulated MRCP reveals persistent enlargement of the pancreatic duct, with a progressive and diffuse parenchymal enhancement corresponding to acinar ductal filling, associated to reduced duodenal filling, up to the genu inferius. (b) Axial MIP from 3D-SSFSE repeated 30 min after secretin injection demonstrates free water in dilated acini showing a hydrographic enhancement of pancreatic parenchyma.
early-stage chronic pancreatitis. In particular, Manfredi et al. [12] demonstrated that on SS-MRCP dilated side branches can be visualized in 63% of cases versus 4% by MRCP in patients suspected of having pancreatic disease. According to these authors, we observed that secretin stimulation improved visualization of abnormal side branches on MRCP from two to 12 cases, with a sensitivity of 85.7% in the detection of chronic pancreatitis. However, duodenal filling appeared reduced (grade 2) only in three out of fourteen patients with mild chronic pancreatitis, showing no clear relationship between morphologic ductal changes and duodenal filling grade, as also reported in other studies [12,16], that described discrepancies between morphologic and functional changes detected in patients with chronic pancreatitis. Therefore, in our two patients with mild chronic pancreatitis was also observed “acinar filling” effect, demonstrating progressive hydrographic enhancement of the pancreatic parenchyma after secretin stimulation. In a previous report, Matos et al. [23], observed 6/90 cases of “acinar filling” after secretin administration and concluded that “acinar filling” might reflect tissue hypertension and/or loss of pancreatic parenchyma compliance; therefore, it is probably an insensitive but specific sign of early chronic pancreatitis. In our study, inflammatory ampullary stenosis was diagnosed in three cases, showing dilation of both main pancreatic duct and common bile duct; after secretin stimulation the calibre of the main pancreatic duct increased dramatically and remained enlarged for all 15 min, with a delayed and relatively reduced pancreatic fluid outflow. Prolonged ductal dilation after stimulation has been demonstrated to be a specific finding in pancreatic outlet obstruction of various causes [19,21]. We also observed one case of juxtapapillary duodenal diverticulum. It is commonly associated with concomitant biliary or pancreatic disease, including choledocholithiasis, and pancreatitis, and some authors hypothesize that it can determine a motility
disorder of the sphincter of Oddi [24]. In our case, conventional MRCP images showed pancreatic duct related to the diverticulum, however, MRCP after secretin stimulation clearly demonstrated pancreatic duct entering into the diverticulum, filled by pancreatic secretion (Fig. 4). In accordance to the data from Mortelé et al. [19], small nonspecific cystic lesions (smaller than 1 cm) were seen in 27.5% (22 patients) using both types of MRCP. Only limited data are available on the prevalence of pancreatic cysts in the general population, and when reported, the frequency at which pancreatic cysts are detected has varied from 2.6% [25] to 36.7% [26], utilizing different imaging techniques (MR, MDCT or both). In our patients conventional MRCP mistakenly diagnosed two cases of alpha loop in the pancreatic duct as small cyst, however, secretin stimulation allowed the visualization of the entire duct, including the looped portion. In our patients with pancreatic cysts, association with pancreas divisum was present in 5 out of 22 cases; when the presence of small non-specific cysts was the only pathologic finding, the aetiology of the biochemical alterations remains unclear. In our study, standards of reference did not differ significantly from of SS-MRCP findings (p = 0.5), while was statistically different from those derived from conventional MRCP (p < 0.0001). The major limitation of our study is that endoscopic retrograde pancreatography was not available as a standard of reference, particularly in patients with pancreas divisum and mild chronic pancreatitis, and for this reason there may be cases that SS-MRCP could not detect these pathologies. However, since these findings can be reliably identified or excluded by SS-MRCP, further invasive diagnostic procedures cannot be justified in asymptomatic patients for ethical reasons. In conclusion, in asymptomatic patients without evident reasons for pancreatic hyperenzymemia, the possible causes should be carefully investigated to exclude the possibility of the existence
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of pancreatic abnormalities. SS-MRCP may represent the best noninvasive diagnostic technique, since it gives morphological and functional information of the pancreas, which has been found to be abnormal in 68.7% of our patients. Conflict of interest All the authors have no conflicts of interest References [1] Gullo L. Chronic nonpathological hyperamylasemia of pancreatic origin. Gastroenterology 1996;110:1905–8. [2] Gullo L. Familial pancreatic hyperenzymemia. Pancreas 2000;20:158–60. [3] Frulloni L, Patrizi F, Bernardoni L, Cavallini G. Pancreatic hyperenzymemia: clinical significance and diagnostic approach. JOP 2005;6:536–51. [4] Gullo L. Benign pancreatic hyperenzymemia. Dig Liv Dis 2007;39:698–702. [5] Soto JA, Barish MA, Yucel EK, Siegenberg D, Terrucci JT, Chuttani R. Magnetic resonance cholangiography: comparison with endoscopic retrograde cholangiopancreatography. Gastroenterology 1996;110:589–97. [6] Matos C, Metens T, Deviere J, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997;203:435–41. [7] Sica GT, Braver J, Cooney MJ, Miller FH, Chai JL, Adams DF. Comparison of endoscopic retrograde cholangiopancreatography with MR cholangiopancreatography in patients with pancreatitis. Radiology 1999;210:605–10. [8] Takehara Y. Fast MR imaging for evaluating the pancreaticobiliary system. Eur J Radiol 1999;29:211–32. [9] Vitellas KM, Keogan MT, Spritzer CE, Rendon CN. MR cholangiopancreatography of bile and pancreatic duct abnormalities with emphasis on the single-shot fast spin-echo technique. Radiographics 2000;20:939–57. [10] Sai JK, Suyama M, Kubokawa Y, Watanabe S. Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography. World J Gastroenterol 2008;14:1218–21. [11] Tamura R, Ishibashi T, Takahashi S. Chronic pancreatitis: MRCP versus ERCP for quantitative caliber measurement and qualitative evaluation. Radiology 2006;238:920–8.
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia Francescamaria Donati a,∗ , Piero Boraschi a , Roberto Gigoni a , Simonetta Salemi a , Lorenzo Faggioni b , Cristina Bertucci b , Claudia Cecchi b , Carlo Bartolozzi b , Fabio Falaschi a a b
2nd Department of Radiology, Pisa University-Hospital, Via Paradisa 2, I-56124 Pisa, Italy Diagnostic and Interventional Radiology, University of Pisa, Via Rome 67, I-56126 Pisa, Italy
a r t i c l e
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Article history: Received 5 May 2009 Received in revised form 8 November 2009 Accepted 11 November 2009 Keywords: MR cholangio-pancreatography Secretin Pancreatic ducts MR Pancreatic hyperenzymemia
a b s t r a c t Purpose: To assess the diagnostic value of secretin-stimulated MRCP (SS-MRCP) compared with conventional MRCP in asymptomatic patients with mild elevations of pancreatic enzymes. Materials and methods: Eighty asymptomatic patients with pancreatic hyperenzymemia underwent MR imaging at 1.5 T-device (Signa EXCITE, GE Healthcare). After the acquisition of axial T1w,T2w sequences, and conventional MRCP, SS-MRCP was performed using a single-slice coronal breath-hold, thick-slab, SSFSE T2w sequence, repeated every 30 s up to 15 min following intravenous injection of secretin (Secrelux® , Sanochemia). Results: On the basis of the standards of reference, our final diagnoses were: negative findings (n = 23), pancreas divisum (n = 22), mild chronic pancreatitis (n = 14), inflammatory ampullary stenosis (n = 3), juxtapapillary duodenal diverticulum (n = 1), small cystic lesions (<1 cm) (n = 22; 5/22 cases associated with pancreas divisum). The image quality of SS-MRCP was significantly higher than that of conventional MRCP (p < 0.0001). Standards of reference did not differ significantly from of SS-MRCP findings (p = 0.5), while was statistically different from those of conventional MRCP (p < 0.0001). A significant difference was found between conventional MRCP and SS-MRCP findings (p < 0.0001). Conclusion: In asymptomatic patients with non-specific pancreatic hyperenzymemia SS-MRCP may represent the best non-invasive diagnostic technique, since it gives morphological and functional information. © 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction An increase in serum levels of pancreatic enzymes is a well-known manifestation of pancreatic disease, especially acute pancreatitis. However, mild elevations are considered non-specific; they have been reported to occur in a variety of pancreatic and extrapancreatic metabolic or structural derangements, such as anatomic variants of the pancreatic duct, recurrent chronic pancreatitis, chronic liver disease, inflammatory bowel disease and so on [1–3]. In addition to this pathological type of hyperenzymemia several non-pathological forms have also been identified, included in a new syndrome named “benign pancreatic hyperenzymemia” [4]. MR cholangio-pancreatography (MRCP) is a non-invasive imaging technique that accurately depicts the morphologic features of the pancreatic ducts. In several studies [5–10], MRCP demonstrates a good correlation with endoscopic retrograde
∗ Corresponding author. Tel.: +39 050 996782; fax: +39 1782211474. E-mail address: [email protected] (F. Donati). 0720-048X/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2009.11.008
cholangio-pancreatography (ERCP) in the evaluation of disease and anatomic variants of the pancreatic ductal system; however, in physiologic conditions the pancreatic ducts, particularly sides branches, are not always depicted [6]. More recently, however, several authors [11–17] have demonstrated that the injection of secretin improves MRCP depiction of the pancreatic ducts, detection and characterization of pancreatic disorders and may allow estimation of exocrine pancreatic reserve. Our study was aimed to assess the diagnostic value of secretinstimulated MRCP (SS-MRCP) compared with conventional MRCP in asymptomatic patients with mild elevations of pancreatic enzymes. 2. Material and methods 2.1. Patients Our study was performed in accordance with the recommendations of our institutional review board and written informed consent was obtained after explanation of the complete examination procedure.
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Between September 2004 and September 2007, 80 asymptomatic patients (38 men and 42 women; mean age, 49.94 ± 8.93 years; age range, 31–68 years) with persistent (for at least 6 months) non-specific serum hyperamylasemia and hyperlipasemia, defined as elevations less than to three times the normal level (normal values are 30–110 U/L for amylase and 13–300 U/L for lipase), were prospectively included in our study group. All patients underwent MR study before and after stimulation with secretin. The following standards of reference were available: duodenal endoscopy with biopsy of the major papilla; intra-operative findings; multi-rows detector CT (MDCT); and clinical (monitoring of pancreatic enzyme levels and symptoms, every 3 months) and imaging (MDCT, at 6 and 18 months, and SS-MRCP at 12 and 24 months) follow-up for at least 12 months. 2.2. MR imaging The MR examinations were performed with superconductive systems operating at 1.5 T (Signa EXCITE, GE Healthcare) with high performance gradients. The phased-array coil was used for both excitation and signal reception. Ten minutes before MRI, a super-paramagnetic suspension (Lumirem® 100 mL, Guerbet) was orally administered to suppress the signal intensity of overlapping fluid-containing organs. Scopolamine methyl-bromide (Buscopan® 20 mg/mL, Boehringer Ingelheim) was intramuscularly administered immediately before starting the examination in order to avoid peristaltic artefacts. The imaging protocol began with axial, breath-hold, with and without fat-suppressed spoiled gradient-echo (SPGR) T1-weighted images (repetition time, 110–130 ms; echo time, minimum full, with effective 2.1–2.3 ms; flip angle, 80◦ ; section thickness, 5 mm; interslice gap, 0.5 mm; matrix size, 256 × 192 pixels; signal averaged, 1; acquisition time, 28–32 s); axial, respiratory-triggered, fat-suppressed, fast spin-echo (FSE) T2-weighted sequence (repetition time automatically adapted to the patient’s breathing pattern, 6000–18000 ms; echo time, 95.5 ms; echo train length, 16; section thickness, 5 mm; interslice gap, 0.5 mm; signals averaged, 3–4; acquisition time, 3–4 min) and/or axial, breath-hold, single-shot fast spin-echo (SSFSE) T2-weighted sequence (repetition time, minimum; echo time, 80 ms; section thickness, 5 mm; interslice gap, 0.5 mm; signal averaged, 0.5–0.6; acquisition time, 18 24 s). Conventional MRCP was performed by means of coronal respiratory-triggered, three-dimensional fast spin-echo (3D FRFSE), heavily T2-weighted sequence (repetition time automatically adapted to the patient’s breathing pattern, 3000–15000 ms; effective echo time, 622 ms; section thickness, 2.4 mm; interslice gap, −1.2 mm; field of view, 35–45 cm; matrix size, 256 × 128 pixels; signal averaged, 2; acquisition time, 3–4 min), and coronal breath-hold, thick-slab, single-shot fast spin-echo (SSFSE) T2w sequence (effective echo time, 1052 ms; thickness, 40–60 mm; field of view, 35–45 cm; matrix size, 256 × 256 pixels; 0.5 signal averaged; acquisition time, 1–2 s for every image). Subsequently, SS-MRCP was performed using a coronal breathhold, thick-slab, SSFSE T2w sequence, with the same parameters reported above, covering the pancreas and adjacent small bowel. After the acquisition of the first image, secretin (Secrelux® , Sanochemia; 1 cU/kg body/weight) was injected intravenously in order to stimulate the pancreas to produce exocrine secretion and single-slice image acquisition was repeated every 30 s up to 15 min. 2.3. Image analysis All MR images were analyzed in consensus by two radiologists (P.B. and R.G.), with more than 15 years experience on biliary and pancreatic MR imaging, who were blinded to patient identification and all results of the standard references or the final diagnoses.
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Image quality before and after secretin stimulation was classified semi-quantitatively using a five-points score: 1, no delineation; 2, poor; 3, sufficient; 4, good; 5, excellent. The visualization of the pancreatic ductal system was classified separately for the main pancreatic duct, and for accessory and side branches. A functional evaluation of the exocrine pancreatic reserve was also performed by a semi-quantitative image analysis of the duodenal filling on the basis of pancreatic secretion after secretin stimulation. The pancreatic fluid outflow was visually analyzed on the image time series by the two observers. The duodenal filling volume was graded according to the scale (0–3) derived by Matos et al. [6]: grade 0, no fluid observed; grade 1, filling limited into the duodenal bulb; grade 2, filling duodenum up to the genu inferius; grade 3, filling duodenum beyond the genu inferius. The exocrine function was considered to be reduced when the duodenal filling volume grade was less than 3. Diagnostic image analysis included the evaluation of the presence of: focal pancreatic lesions and their relationship to the pancreatic ductal system; anatomic variants of the pancreatic duct; abnormal side branches; morphologic changes of the main pancreatic duct; and hepato-biliary abnormalities. Chronic pancreatitis was diagnosed on the basis of the Cambridge classification if at least three abnormal side branches or main pancreatic ductal irregularities were present [10]. MR images before and after secretin stimulation were evaluated on a dedicated workstation (Advantage Windows 4.4; GE Healthcare) separately and in a randomized fashion. These results were correlated with the final diagnoses on the basis of the previously mentioned standards of reference. 2.4. Statistical analysis The distribution of the qualitative variables was expressed as the relative frequency of the various modalities under observation. The distribution of the quantitative variables was expressed as the mean, standard deviation, minimum, maximum and number of observations. The comparison between image quality scores obtained before and after secretin stimulation was evaluated by means of two-tailed Wilcoxon rank test. The proportion of agreement among conventional MRCP, SS-MRCP and standards of reference was assessed by using McNemar test. Statistical analysis was carried out through the VassarStats website (http://faculty.vassar.edu/lowry/VassarStats.html). A threshold of p < 0.05 was considered for statistical significance. 3. Results On the basis of the standards of reference, our final diagnoses were: 23 negative findings; 22 cases of pancreas divisum; 14 cases of mild chronic pancreatitis; 3 cases of inflammatory ampullary stenosis; one case of juxtapapillary duodenal diverticulum; and 22 cases of microcysts (in 5 patients associated with pancreas divisum) (Table 1). All 80 MR studies were considered diagnostic by the reviewers. All patients well tolerated the examination, and no side effect was reported after secretin administration. Image quality findings are summarized in Table 2. The image quality of SS-MRCP was significantly higher than that of conventional MRCP, both overall (p < 0.0001) and as regards depiction of accessory ducts and/or side branches (p < 0.0001). Diagnoses before and after secretin stimulation are reported in Table 3. Conventional MRCP showed pancreatic abnormalities in 40 out of 80 (50%) patients, while after secretin stimulation pancreatic abnormalities were observed in 55 out of 80 (68.7%) patients. The primary diagnosis was changed after secretin stimulation in 22 out of 80 (27.5%) patients.
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F. Donati et al. / European Journal of Radiology 75 (2010) e38–e44 Table 3 Imaging findings on conventional and SS-MRCP.
Table 1 Final diagnoses on the basis of the standards of reference. No. of patients
Standards of reference
Pancreas divisum Mild chronic pancreatitis
22 14
Ampullary stenosis Juxtapapillary duodenal diverticulum Small cysts (<1 cm)
3 1 22
Negative findings
23
Imaging follow-up MDCT; clinical and imaging follow-up Endoscopic biopsy Surgery MDCT; clinical and imaging follow-up MDCT; clinical and imaging follow-up
Final diagnosis
Diagnosis
A pancreas divisum was found in 12 patients before and in 22 patients after secretin administration. Both dorsal and ventral pancreatic ducts, with predominant drainage through the minor papilla, were recognized in all 22 cases of pancreas divisum after secretin injection (Fig. 1). Morphologic changes compatible with mild chronic pancreatitis, characterized by the presence of at least three abnormal side branches in the head and tail, were identified in two cases on conventional MRCP, and in 12 cases on SS-MRCP; secretin stimulation improved visualization of both main pancreatic duct and the side branches (from two to 12 cases) particularly at the level of the tail (Fig. 2), with a sensitivity of 85.7% in the detection of chronic pancreatitis. However, SS-MRCP did not identify two cases of mild chronic pancreatitis (two false negative results), diagnosed at 6 and 12 months imaging follow-up, showing the first case ductal irregularity and parenchymal micro-calcifications at MDCT, and the second one ductal irregularities in the head and body and dilated side braches in the tail at SS-MRCP. In three cases, inflammatory ampullary stenosis was diagnosed on both the techniques, showing the dilation of main pancreatic duct and common bile duct; in these cases after secretin stimulation the calibre of the main pancreatic duct increased and remained enlarged for all 15 min (Fig. 3). MR images showed also one case of juxtapapillary duodenal diverticulum, that determined dislocation of adjacent Wirsung; furthermore, SS-MRCP well demonstrated the filling of diverticulum by pancreatic secretion (Fig. 4). Small non-specific cystic lesions (<1 cm) were also seen in 22 patients (associated with pancreas divisum in 5 out of 22 cases) on both types of MRCP; however, conventional MRCP mistakenly diagnosed two cases of alpha loop in the pancreatic duct as small pancreatic cyst (two false positive results). After secretin injection a normal duodenal filling, corresponding to grade 3, was observed in 74 patients. Pancreatic fluid outflow appeared reduced (grade 1 in two cases and grade 2 in one) in the three patients with inflammatory ampullary stenosis. Grade 2 of duodenal filling was also appreciable in three patients with mild chronic pancreatitis, suggesting reduced exocrine pancreatic reserve; in two out of these three cases SS-MRCP also showed “acinar filling”, demonstrating progressive hydrographic enhancement of the pancreatic parenchyma (Fig. 5). Standards of reference did not differ significantly from of SSMRCP findings (p = 0.5), while was statistically different from those derived from conventional MRCP (p < 0.0001). Furthermore, a sig-
Conventional MRCP
Pancreas divisum (n = 22) Mild chronic pancreatitis (n = 14) Ampullary stenosis (n = 3) Juxtapapillary duodenal diverticulum (n = 1) Small cysts (<1 cm) (n = 22)
*
SS-MRCP 22 12* 3 1 22
12 2* 3 1 24**
Note: * false negative; ** false positive.
nificant difference was also found out between conventional MRCP and SS-MRCP findings (p < 0.0001). 4. Discussion The causes of increased levels of serum pancreatic enzymes may be related to pancreatic disease. In the absence of pathologies of the pancreas, the possible cause of an increased enzyme release from the pancreas is generally a mild obstruction of the pancreatic ductal system, that alters the normal exocytosis process in the acinar cells [3]. Because of the large spreading of asymptomatic patients with increased pancreatic enzymes levels and without evident reasons for biochemical alteration, the possible causes should be carefully investigated with instrumental examination to exclude pancreatic disorders in clinical practice. MRCP has evolved as an accurate imaging technique for the non-invasive evaluation of the pancreato-biliary tract [5–10,18]. The diagnostic accuracy of MRCP is comparable to that of ERCP in the evaluation of disease and anatomic variants of the pancreatic ducts; in physiologic conditions, however, the pancreatic ducts, particularly sides branches, are not always depicted [6,7]. Several authors [11–17] reported that MRCP after secretin stimulation shows a significant improvement of visualization of the main pancreatic duct and the Santorini duct in all patients having a normal exocrine pancreatic function. Secretin administration stimulates fluid and bicarbonate secretion by the exocrine pancreas and simultaneously increases tonus of the sphincter of Oddi, inducing a transitory dilation of the main pancreatic duct, which improves visualization. In addition, the degree of duodenal filling resulting from the drainage of pancreatic fluid can be evaluated as an indirect measure of exocrine pancreatic function [16]. Therefore, various reports [11,13,15] have demonstrated that SS-MRCP is useful for the morphologic and functional evaluation of the pancreatic duct. To our knowledge, few reports have focused on the evaluation of asymptomatic patients with mild pancreatic hyperenzymemia and for this reason we aimed to investigate the spectrum of SS-MRCP findings in this group of patients. On the first report focused on this matter from an imaging perspective Mortelé et al. [19] studied these asymptomatic biochemical alterations using conventional MRCP, without secretin stimulation. Their results suggested that 31 out of 54 patients (57%) presented pancreatic abnormalities on MRCP. More recently, Testoni et al. [20] compared 25 asymptomatic patients with pancreatic hyperenzymemia with 28 normal controls, all studied with MRCP after secretin injection, and demon-
Table 2 Image quality before and after secretin stimulation.
Main duct C-MRCP Main duct SS-MRCP Accessory/side branches C-MRCP Accessory/side branches SS-MRCP
Grade 1 (n=)
Grade 2 (n=)
Grade 3 (n=)
Grade 4 (n=)
Grade 5 (n=)
9 – 62 43
53 – 11 2
17 – 6 –
1 27 1 17
– 53 – 18
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Fig. 1. (a–c) 49-year-old man with recurrent (since 15 months) asymptomatic increase of pancreatic enzyme levels. (a) MRCP obtained using coronal breath-hold, thick-slab, SSFSE T2w sequence MRCP reveals only the dorsal pancreatic duct before secretin administration. (b) MRCP obtained 3 min after secretin injection demonstrates both the ventral (arrow) and the dorsal pancreatic duct, without connection between them and prompt outflow of pancreatic secretion via the minor papilla, corresponding to pancreas divisum with dominant dorsal duct. (c) MRCP obtained 15 min after secretin injection shows normal duodenal filling beyond the genu inferius.
strated abnormal pancreatic morphological findings in 13/25 patients (52%) and 1/28 controls (3.6%) (p < 0.001). These authors concluded that MRCP after secretin administration is to be recommended, instead of MRCP alone, in the diagnostic work-up of asymptomatic patients with pancreatic hyperenzymemia.
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Fig. 2. (a–c) 52-year-old woman with persistent (for at least 9 months) non-specific serum hyperamylasemia and hyperlipasemia. (a) MRCP obtained before secretin injection shows a normal main pancreatic duct. (b) Three minutes after secretin stimulation, MRCP reveals side branches dilation, particularly at the level of the head and tail diagnosed as mild chronic pancreatitis. (c) MRCP obtained 15 min after secretin injection demonstrates normal duodenal filling beyond the genu inferius, interpreted as preserved pancreatic exocrine reserve.
According to their results, in our study, conventional MRCP showed abnormalities of the pancreas in 40 out of 80 (50%) patients; while SS-MRCP identified positive results in 55 out of 80 (68.7%) patients, with a significant difference between conventional MRCP and SS-MRCP findings (p < 0.0001). Furthermore, primary diagnosis was changed in 22 out of 80 (27.5%) patients. The most common pancreatic finding identified in our series was pancreas divisum, observed in 22 patients (27.5%), while the prevalence in the normal population is of 5–14% [19]. Before secretin injection ventral duct was not seen in 10 cases, while after secretin
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Fig. 3. (a–c) 69-year-old man with asymptomatic recurrent increase (since 12 months) of pancreatic enzyme levels. (a) MRCP obtained before secretin administration reveals distal common bile duct stenosis, with consequent dilatation of extra-hepatic bile ducts. Head portion of pancreatic duct is only slightly dilated. (b) MRCP obtained 3 min after secretin injection shows increasing diameter of pancreatic duct. Compared with A, there is improved visualization of pancreatic ductal irregularities and of duct narrowing in head portion (arrow). (c) MRCP obtained 15 min after secretin injection demonstrates duodenal filling up to genu inferius (grade 2), interpreted as reduced exocrine pancreatic reserve. Endoscopic evaluation with papillary biopsy diagnosed inflammatory ampullary stenosis.
stimulation it was recognized in all cases; predominant drainage through the minor papilla was always demonstrated. Postulated that, in pancreas divisum, pancreatic hyperenzymes may result from mild obstruction of outflow of pancreatic secretion through the minor papilla [19–22], SS-MRCP can be an important physiologic challenge to assess the relevance of any degree of papillary stenosis [16]. Morphologic changes compatible with mild chronic pancreatitis were demonstrated in 12 patients on SS-MRCP. Several authors
Fig. 4. (a–c) 57-year-old woman with juxtapapillary duodenal diverticulum and recurrent (since 18 months) non-specific increase of pancreatic enzyme levels. (a) MRCP obtained before secretin administration shows the main pancreatic duct with abnormal and irregular course and demonstrates a voluminous kinking at the level of the head. (b) MRCP obtained 10 min after secretin injection visualizes increasing diameter of pancreatic duct and fluid-filled juxta-duodenal lumen (arrow). (c) Coronal-oblique MIP from 3D-SSFSE repeated 20 min after secretin injection demonstrates fluid-filled juxtapapillary duodenal diverticulum (arrow). The communication between main pancreatic duct and diverticulum was confirmed at surgery.
[6,12,15,17] reported the usefulness of SS-MRCP in the diagnosis of chronic pancreatitis. Hellerhoff et al. [16] reported that the overall sensitivity of MRCP in the detection of chronic pancreatitis increased from 77% to 89% after secretin injection and that the benefit of secretin administration is even greater in the case of
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Fig. 5. (a and b) 62-year-old man with asymptomatic persistent (for at least 6 months) increase of pancreatic enzyme levels. (a) Secretin-stimulated MRCP reveals persistent enlargement of the pancreatic duct, with a progressive and diffuse parenchymal enhancement corresponding to acinar ductal filling, associated to reduced duodenal filling, up to the genu inferius. (b) Axial MIP from 3D-SSFSE repeated 30 min after secretin injection demonstrates free water in dilated acini showing a hydrographic enhancement of pancreatic parenchyma.
early-stage chronic pancreatitis. In particular, Manfredi et al. [12] demonstrated that on SS-MRCP dilated side branches can be visualized in 63% of cases versus 4% by MRCP in patients suspected of having pancreatic disease. According to these authors, we observed that secretin stimulation improved visualization of abnormal side branches on MRCP from two to 12 cases, with a sensitivity of 85.7% in the detection of chronic pancreatitis. However, duodenal filling appeared reduced (grade 2) only in three out of fourteen patients with mild chronic pancreatitis, showing no clear relationship between morphologic ductal changes and duodenal filling grade, as also reported in other studies [12,16], that described discrepancies between morphologic and functional changes detected in patients with chronic pancreatitis. Therefore, in our two patients with mild chronic pancreatitis was also observed “acinar filling” effect, demonstrating progressive hydrographic enhancement of the pancreatic parenchyma after secretin stimulation. In a previous report, Matos et al. [23], observed 6/90 cases of “acinar filling” after secretin administration and concluded that “acinar filling” might reflect tissue hypertension and/or loss of pancreatic parenchyma compliance; therefore, it is probably an insensitive but specific sign of early chronic pancreatitis. In our study, inflammatory ampullary stenosis was diagnosed in three cases, showing dilation of both main pancreatic duct and common bile duct; after secretin stimulation the calibre of the main pancreatic duct increased dramatically and remained enlarged for all 15 min, with a delayed and relatively reduced pancreatic fluid outflow. Prolonged ductal dilation after stimulation has been demonstrated to be a specific finding in pancreatic outlet obstruction of various causes [19,21]. We also observed one case of juxtapapillary duodenal diverticulum. It is commonly associated with concomitant biliary or pancreatic disease, including choledocholithiasis, and pancreatitis, and some authors hypothesize that it can determine a motility
disorder of the sphincter of Oddi [24]. In our case, conventional MRCP images showed pancreatic duct related to the diverticulum, however, MRCP after secretin stimulation clearly demonstrated pancreatic duct entering into the diverticulum, filled by pancreatic secretion (Fig. 4). In accordance to the data from Mortelé et al. [19], small nonspecific cystic lesions (smaller than 1 cm) were seen in 27.5% (22 patients) using both types of MRCP. Only limited data are available on the prevalence of pancreatic cysts in the general population, and when reported, the frequency at which pancreatic cysts are detected has varied from 2.6% [25] to 36.7% [26], utilizing different imaging techniques (MR, MDCT or both). In our patients conventional MRCP mistakenly diagnosed two cases of alpha loop in the pancreatic duct as small cyst, however, secretin stimulation allowed the visualization of the entire duct, including the looped portion. In our patients with pancreatic cysts, association with pancreas divisum was present in 5 out of 22 cases; when the presence of small non-specific cysts was the only pathologic finding, the aetiology of the biochemical alterations remains unclear. In our study, standards of reference did not differ significantly from of SS-MRCP findings (p = 0.5), while was statistically different from those derived from conventional MRCP (p < 0.0001). The major limitation of our study is that endoscopic retrograde pancreatography was not available as a standard of reference, particularly in patients with pancreas divisum and mild chronic pancreatitis, and for this reason there may be cases that SS-MRCP could not detect these pathologies. However, since these findings can be reliably identified or excluded by SS-MRCP, further invasive diagnostic procedures cannot be justified in asymptomatic patients for ethical reasons. In conclusion, in asymptomatic patients without evident reasons for pancreatic hyperenzymemia, the possible causes should be carefully investigated to exclude the possibility of the existence
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of pancreatic abnormalities. SS-MRCP may represent the best noninvasive diagnostic technique, since it gives morphological and functional information of the pancreas, which has been found to be abnormal in 68.7% of our patients. Conflict of interest All the authors have no conflicts of interest References [1] Gullo L. Chronic nonpathological hyperamylasemia of pancreatic origin. Gastroenterology 1996;110:1905–8. [2] Gullo L. Familial pancreatic hyperenzymemia. Pancreas 2000;20:158–60. [3] Frulloni L, Patrizi F, Bernardoni L, Cavallini G. Pancreatic hyperenzymemia: clinical significance and diagnostic approach. JOP 2005;6:536–51. [4] Gullo L. Benign pancreatic hyperenzymemia. Dig Liv Dis 2007;39:698–702. [5] Soto JA, Barish MA, Yucel EK, Siegenberg D, Terrucci JT, Chuttani R. Magnetic resonance cholangiography: comparison with endoscopic retrograde cholangiopancreatography. Gastroenterology 1996;110:589–97. [6] Matos C, Metens T, Deviere J, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997;203:435–41. [7] Sica GT, Braver J, Cooney MJ, Miller FH, Chai JL, Adams DF. Comparison of endoscopic retrograde cholangiopancreatography with MR cholangiopancreatography in patients with pancreatitis. Radiology 1999;210:605–10. [8] Takehara Y. Fast MR imaging for evaluating the pancreaticobiliary system. Eur J Radiol 1999;29:211–32. [9] Vitellas KM, Keogan MT, Spritzer CE, Rendon CN. MR cholangiopancreatography of bile and pancreatic duct abnormalities with emphasis on the single-shot fast spin-echo technique. Radiographics 2000;20:939–57. [10] Sai JK, Suyama M, Kubokawa Y, Watanabe S. Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography. World J Gastroenterol 2008;14:1218–21. [11] Tamura R, Ishibashi T, Takahashi S. Chronic pancreatitis: MRCP versus ERCP for quantitative caliber measurement and qualitative evaluation. Radiology 2006;238:920–8.
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