Jin Kan Sai, Masafumi Suyama, Yoshihiro Kubokawa, Sumio Watanabe, Department of Gastroenterology. Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

Correspondence to: Dr. Jin Kan Sai, Department of Gastro-enterology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. jinkans@med.juntendo.ac.jp

Telephone: +81-3-58021061    Fax: +81-3-56845960

Received: September 8, 2007  Revised: November 16, 2007

Abstract

AIM: To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis.

METHODS: Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison.

RESULTS: The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (k statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent.

CONCLUSION: Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

© 2008 WJG. All rights reserved.

Key words: Magnetic resonance cholangiopancreatography; Endoscopic retrograde cholangiopancreatography; Mild; Chronic pancreatitis; Diagnosis

Peer reviewers: Giuseppe Brisinda, MD, Department of Surgery, Catholic School of Medicine “Agostino Gemelli”, Largo Agostino Gemelli 8-00168 Rome, Italy; Yoshiharu Motoo, MD, PhD, FACP, FACG, Professor and Chairman, Department of Medical Oncology, Kanazawa Medical University,1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan; William Dickey, Altnagelvin Hospital, Londonderry, BT47 6SB, Northern Ireland, United Kingdom

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(8): 1218-1221  Available from: URL: http://www.wjgnet.com/1007-9327/14/1218.asp  DOI: http://dx.doi.org/10.3748/wjg.14.1218

INTRODUCTION

Chronic pancreatitis is morphologically characterized by irregular sclerosis associated with destruction and permanent loss of the exocrine parenchyma which may be either, focal, segmental or diffuse. These changes may present together with varying degrees of dilatation of the duct system at different segments^[1]. Chronic pancreatitis is classified according to morphologic changes of the pancreatic ducts, as defined in the 1983 Cambridge Symposium^[2].

MR cholangiopancreatography (MRCP) is a useful non-invasive technique to depict the projection images of the pancreatico-biliary tree, and is expected to become a valuable alternative to endoscopic retrograde cholangiopancreatography (ERCP)^[3-8]. However, visualization of the branch pancreatic ducts by MRCP is not good^[9-11], and there are few reports about the diagnostic value of MRCP in mild chronic pancreatitis (Cambridge classification). On the other hand, secretin injection-MRCP might allow better visualization of the pancreatic ductal system^[12-16].

The purpose of this study was to evaluate the usefulness of secretin injection-MRCP for the diagnosis of abnormal branch pancreatic duct in patients with mild chronic pancreatitis.

MATERIALS AND METHODS

Patients

The MRCP image obtained after secretin injection was examined in 16 patients (32-39 y.o.; mean 36 y.o.) having mild chronic pancreatitis according to the Cambridge classification, and in 12 control subjects (31-37 y.o.; mean 35 y.o.) showing no abnormal findings on the pancreatogram, who had already undergone ERCP. In the Cambridge classification mild chronic pancreatitis is defined as “more than 3 abnormal side branches with a normal main pancreatic duct”. In the present study, we selected patients in their 30’s, because we wanted to exclude those with ductal changes associated with aging. In all the patients the maximum diameter of the main pancreatic duct was within 2 mm and the ultrasonogram and CT revealed no findings suggestive of chronic pancreatitis, such as atrophy, calcification, dilatation or stenosis of the pancreatic duct. The control subjects had no pancreatic diseases and were selected from a population that had undergone ERCP for a suspected biliary disease. Patients with mild chronic pancreatitis were selected from a population that had been subjected to ERCP for recurrent attacks of abdominal pain associated with increased serum levels of amylase and lipase in the absence of conclusive US or CT findings of chronic pancreatitis. The symptomatic period was between 15 and 54 mo. Secretin injection-MRCP was performed within 4 wk after ERCP. Informed consent was obtained from all patients after explanation of the examination process. The study protocol was approved by the ethical committee of our institution.

MRCP

After a 6-h fast, MR studies were performed on a 1.5 T scanner using a phased-array multi-coil. With the patients in the supine position, 100 U of secretin (Eisai Corporation, Tokyo, Japan) was injected intravenously. Half-Fourier fast echo sequences with the single slice method were obtained in the coronal plane and left and right oblique planes to emphasize the pancreatic body, head and tail, respectively. MRCP images of axial planes were also added on demand. The sequence parameters were: effective echo time, 250 ms; echo train length, 212; matrix, 384 × 384; FOV, 25 to 35 cm. A thin slice, thickness of 10-30 mm, was adopted to delineate the fine structure of the minimally dilated branches. The acquisition time for an image was 3 s with complete breath-holding. Acquisition was repeated every 30 s during 10 min.

Image analysis

Only clear MRCP images of the pancreatic ducts were regarded as acceptable. MRCP images were reviewed using ERCP as the gold standard. Two sets of MRCP films and one set of ERCP films were prepared so that each reviewer could work separately on the films. MRCP images were interpreted independently by two reviewers (Sai J and Takayashi Y) and ERCP images by another reviewer (Kubokawa Y); all of them were experienced in pancreaticobiliary imaging. Each MRCP and ERCP film was randomly numbered, and reviewers were blinded to the clinical information associated with each film. Abnormal branches of the pancreatic ducts were documented with markings on the duplicate films of ERCP and MRCP by each reviewer, who did not participate in the examination; visible branch pancreatic ducts were regarded as abnormal branch pancreatic ducts on MRCP images because they are not detectable on MRCP except in pathologic cases^[10]. Then MRCP images were compared with the ERCP images for the number and location of the abnormal branch pancreatic ducts, lesion by lesion under consensus.

Statistical analysis

The sensitivity and specificity for the diagnosis of abnormal branch pancreatic ducts and mild chronic pancreatitis (Cambridge classification) determined by each reviewer was examined. Regarding the diagnosis of ectatic branch pancreatic duct and mild chronic pancreatitis on MRCP images, the interobserver agreement was analyzed with statistics: values were classified as excellent (above 0.75), fair to good (0.40 to 0.75), or poor (below 0.40).

RESULTS

Successful MRCP images were obtained after secretin injection in patients with mild chronic pancreatitis and control subjects. The rates for visualization of the main pancreatic duct on MRCP were 100%.

Abnormal branch ducts delineated on MRCP images correlated with ERCP images, lesion by lesion. The sensitivity and specificity for the diagnosis of abnormal branch pancreatic ducts determined by the two reviewers were 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas, respectively (Table 1a, b). The sensitivity and specificity for the diagnosis of mild chronic pancreatitis (Cambridge classification) was 56%-63% and 92%-92%, respectively (Table 2). Interobserver agreement (κ statistics) for identifying abnormal branch pancreatic ducts and for diagnosing mild chronic pancreatitis was good to excellent (Table 3).

DISCUSSION

Early-stage chronic pancreatitis is difficult to diagnose because less obvious changes occur over time, before the development of overt exocrine or endocrine insufficiency and visible structural abnormalities^[17]. Therefore, a major diagnostic challenge occurs when patients have clinical signs suggestive of chronic pancreatitis, in the absence of demonstrable pancreatic abnormalities on ultrasonography and CT. Reversely, in patients with advanced disease, findings such as atrophy, calcification, dilatation and stenosis of the pancreatic duct are obvious^[18]. One of the earliest findings of chronic pancreatitis is an abnormal branch of the pancreatic duct detected by ERCP^[2,18]. ERCP is the sensitive method for the diagnosis of early-stage chronic pancreatitis^[19-21]; however, it is invasive and associated with complications^[22,23], because sufficient contrast medium must be injected to the peripheral branches of the pancreatic ducts when mild changes of chronic pancreatitis are sought^[24].

Today, diagnostic ERP is challenged by MRCP, which is a noninvasive alternative to diagnostic ERP for the evaluation of normal and diseased pancreatic ducts^[5-9]. However, it is difficult to delineate minimally dilated branch pancreatic ducts on MRCP despite its improved resolution because while on ERCP images the collapsed branches and main pancreatic duct are distended by the contrast medium, MRCP reflects the physiologic state of the pancreatic duct.

Since Takehara et al^[10] first reported the MRCP images of moderate to severe chronic pancreatitis obtained after the injection of secretin; several authors have reported the usefulness of secretin injection-MRCP in the diagnosis of chronic pancreatitis^[12-15]. Secretin stimulates fluid secretion in the ductal system; and increases the tonus of the sphincter of Oddi during the first 5 min, inhibiting the release of fluid through the papilla of Vater^[9]. Therefore, secretin increases the absolute volume of intraductal free water and fills the collapsed branches with fluid^[10], facilitating the detection of mild ductal changes in patients with mild chronic pancreatitis, even when no abnormalities can be demonstrated by MRCP under physiologic conditions. According to Mansfredi et al^[25], visualization of the pancreatic duct branches improved from 71% to 100% in 93 patients with severe chronic pancreatitis and from 4% to 63% in 84 patients suspected of having pancreatic disease. Since the pancreatic juice secretion decreases in patients with advanced chronic pancreatitis, secretin injection-MRCP could be of diagnostic value for those with early-stage chronic pancreatitis, although the occurrence of mild chronic pancreatitis was underestimated by secretin injection-MRCP compared with ERCP in the present study.

There were some limitations to the present study. MRCP should be interpreted by someone blinded to the clinical information to avoid biases. Furthermore, although ERCP was chosen as the gold standard, it is well known that chronic pancreatitis may exist in the presence of a normal pancreatogram. Besides, parenchymal abnormalities may precede ductal and functional changes, and EUS is considered a more sensitive test for parenchymal abnormalities^[26-30]. Therefore, the diagnostic value of secretin injection-MRCP for mild chronic pancreatitis might be limited.

In conclusion, secretin injection-MRCP might allow an earlier diagnosis of chronic pancreatitis and reduce the rate of false-negative cases detected with MRCP.

COMMENTS

Background

Early-stage chronic pancreatitis is difficult to diagnose because less obvious changes occur over time. One of the earliest findings of chronic pancreatitis is an abnormal branch of the pancreatic duct detected by endoscopic retrograde cholangiopancreatography (ERCP). On the other hand, MR cholangiopancreatography (MRCP) is expected to become valuable alternative to ERCP. However, diagnosis of mild ductal changes of chronic pancreatitis using magnetic resonance cholangiopancreatography (MRCP) is quite challenging, because visualization of the branch pancreatic ducts is not good.

Research frontiers

We examined the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge classification) using ERCP for comparison, and there were no other related or similar studies.

Innovation and breakthrough

The sensitivity and specificity for the diagnosis of mild chronic pancreatitis (Cambridge classification) was 56%-63% and 92%-92%, respectively. Secretin injection-MRCP might allow an early diagnosis of chronic pancreatitis.

Application

The application of this study could be expanded to diagnose early chronic pancreatitis in larger series.

Terminology

Secretin injection-MRCP was acquired as follows: with the patients in the supine position, 100 U of secretin was injected intravenously. MRCP was repeated every 30 s during 10 min.

Peer review

Secretin injection-MRCP could be a useful method for the diagnosis of mild chronic pancreatitis (Cambridge Classification), although the occurrence was underestimated compared with ERCP.

REFERENCES

1     Hayakawa T, Kondo T, Shibata T, Noda A, Suzuki T, Nakano S. Relationship between pancreatic exocrine function and histological changes in chronic pancreatitis. Am J Gastroenterol 1992; 87: 1170-1174   PubMed

2     Sarner M, Cotton PB. Classification of pancreatitis. Gut 1984; 25: 756-759   PubMed

3     Wallner BK, Schumacher KA, Weidenmaier W, Friedrich JM. Dilated biliary tract: evaluation with MR cholangiography with a T2-weighted contrast-enhanced fast sequence. Radiology 1991; 181: 805-808   PubMed

4     Morimoto K, Shimoi M, Shirakawa T, Aoki Y, Choi S, Miyata Y, Hara K. Biliary obstruction: evaluation with three-dimensional MR cholangiography. Radiology 1992; 183: 578-580   PubMed

5     Soto JA, Barish MA, Yucel EK, Siegenberg D, Terrucci JT, Chuttani R. Magnetic resonance cholangiography: comparison with endoscopic retrograde cholangiopancreatography. Gastroenterology 1996; 110: 589-597

6     Fulcher AS, Turner MA, Capps GW, Zfass AM, Baker KM. Half-Fourier RARE MR cholangiopancreatography: experience in 300 subjects. Radiology 1998; 207: 21-32   PubMed

7     Miyazaki T, Yamashita Y, Tsuchigame T, Yamamoto H, Urata J, Takahashi M. MR cholangiopancreatography using HASTE (half-Fourier acquisition single-shot turbo spin-echo) sequences. AJR Am J Roentgenol 1996; 166: 1297-1303

8     Sai JK, Ariyama J. MRCP: early diagnosis of pancreatobiliary diseases. 1st ed. Tokyo: Springer, 2000: 1-155

9     Cappeliez O, Delhaye M, Deviere J, Le Moine O, Metens T, Nicaise N, Cremer M, Stryuven J, Matos C. Chronic pancreatitis: evaluation of pancreatic exocrine function with MR pancreatography after secretin stimulation. Radiology 2000; 215: 358-364

10   Takehara Y, Ichijo K, Tooyama N, Kodaira N, Yamamoto H, Tatami M, Saito M, Watahiki H, Takahashi M. Breath-hold MR cholangiopancreatography with a long-echo-train fast spin-echo sequence and a surface coil in chronic pancreatitis. Radiology 1994; 192: 73-78   PubMed

11   Takehara Y. Can MRCP replace ERCP? J Magn Reson Imaging 1998; 8: 517-534   PubMed

12   Matos C, Metens T, Deviere J,Nicaise N, Braude P, Van Yperen G, Cremer M, Struyven J. Pancreatic duct: Morphologic and functional evaluation with dynamic MR pancreatography after secretin injection. Radiology 1997; 203: 435-441   PubMed

13   Sica GT, Braver J, Cooney MJ, Miller FH, Chai JL, Adams DF. Comparison of endoscopic retrograde cholangiopan-creatography with MR cholangiopancreatography in patients with pancreatitis. Radiology 1999; 210: 605-610   PubMed

14   Hellerhoff KJ, Helmberger H 3rd, Rosch T, Settles MR, Link TM, Rummeny EJ. Dynamic MR pancreatography after secretin administration: image quality and diagnostic accuracy. AJR Am J Roentgenol 2002; 179: 121-129   PubMed

15   Takehara Y. Fast MR imaging for evaluating the pancreaticobiliary system. Eur J Radiol 1999; 29: 211-232   PubMed

16   Mariani A, Curioni S, Zanello A, Passaretti S, Masci E, Rossi M, Del Maschio A, Testoni PA. Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis. Gastrointest Endosc 2003; 58: 847-852   PubMed

17   Forsmark CE. The diagnosis of chronic pancreatitis. Gastrointest Endosc 2000; 52: 293-298   PubMed

18   Bozkurt T, Braun U, Leferink S, Gilly G, Lux G. Comparison of pancreatic morphology and exocrine functional impairment in patients with chronic pancreatitis. Gut 1994; 35: 1132-1136   PubMed

19   Dominguez-Munoz JE, Manes G, Pieramico O, Buchler MW, Malfertheiner P. Effect of pancreatic ductal and parenchymal changes on exocrine function in chronic pancreatitis. Pancreas 1995; 10: 31-35   PubMed

20   Malfertheiner P, Buchler M, Stanescu A, Ditschuneit H. Exocrine pancreatic function in correlation to ductal and parenchymal morphology in chronic pancreatitis. Hepatogastroenterology 1986; 33: 110-114   PubMed

21   Braganza JM, Hunt LP, Warwick F. Relationship between pancreatic exocrine function and ductal morphology in chronic pancreatitis. Gastroenterology 1982; 82: 1341-1347   PubMed

22   Bilbao MK, Dotter CT, Lee TG, Katon RM. Complications of endoscopic retrograde cholangiopancreatography (ERCP). A study of 10,000 cases. Gastroenterology 1976; 70: 314-320   PubMed

23   Zimmon DS, Falkenstein DB, Riccobono C, Aaron B. Complications of endoscopic retrograde cholangiopancreatography. Analysis of 300 consecutive cases. Gastroenterology 1975; 69: 303-309   PubMed

24   Sahai AV, Zimmerman M, Aabakken L, Tarnasky PR, Cunningham JT, van Velse A, Hawes RH, Hoffman BJ. Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography. Gastrointest Endosc 1998; 48: 18-25   PubMed

25   Manfredi R, Costamagna G, Brizi MG, Maresca G, Vecchioli A, Colagrande C, Marano P. Severe chronic pancreatitis versus suspected pancreatic disease: dynamic MR cholangio-pancreatography after secretin stimulation. Radiology 2000; 214: 849-855   PubMed

26   Catalano MF, Lahoti S, Geenen JE, Hogan WJ. Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis. Gastrointest Endosc 1998; 48: 11-17   PubMed

27   Sahai AV, Mishra G, Penman ID, Williams D, Wallace MB, Hadzijahic N, Pearson A, Vanvelse A, Hoffman BJ, Hawes RH. EUS to detect evidence of pancreatic disease in patients with persistent or nonspecific dyspepsia. Gastrointest Endosc 2000; 52: 153-159   PubMed

28   Kahl S, Glasbrenner B, Leodolter A, Pross M, Schulz HU, Malfertheiner P. EUS in the diagnosis of early chronic pancreatitis: a prospective follow-up study. Gastrointest Endosc 2002; 55: 507-511   PubMed

29   Nattermann C, Goldschmidt AJ, Dancygier H. Endoso-nography in chronic pancreatitis--a comparison between endoscopic retrograde pancreatography and endoscopic ultrasonography. Endoscopy 1993; 25: 565-570   PubMed

30   Wiersema MJ, Hawes RH, Lehman GA, Kochman ML, Sherman S, Kopecky KK. Prospective evaluation of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in patients with chronic abdominal pain of suspected pancreatic origin. Endoscopy 1993; 25: 555-564   PubMed

S- Editor  Chen X    L- Editor  Alpini GD    E- Editor  Wang HF

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