Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed en- hancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

Importance of early diagnosis of pancreaticobiliary maljunction without biliary dilatation

AIM:To clarify the strategy for early diagnosis of pancreaticobiliary maljunction(PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.METHODS:The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography(ERCP).Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM.Of these,patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation.The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated.Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.RESULTS:Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain(n = 16) or jaundice(n = 12).Radical surgery for gallbladder cancer was only possible in 11 patients(31%) and only 4 patients(11%) survived for 5 years.Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography(MRCP).The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer.All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred.Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls,and hyperplastic changes,hypertrophic muscular layer,subserosal fibrosis,and adenomyomatosis were detected in 7(88%),5(63%),7(88%) and 5(63%) patients,respectively.Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.CONCLUSION:To detect PBM without biliary dilatation before onset of gallbladder cancer,we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.

Differences between diffuse and focal autoimmune pancreatitis

AIM:To investigate differences in clinical features between diffuse-and focal-type autoimmune pancreatitis(AIP).METHODS:Based on radiological findings by computed tomography and/or magnetic resonance imaging,we divided 67 AIP patients into diffuse type(D type) and focal type(F type).We further divided F type into head type(H type) and body and/or tail type(B/T type) according to the location of enlargement.Finally,we classified the 67 AIP patients into three groups:D type,H type and B/T type.We compared the three types of AIP in terms of clinical,laboratory,radiological,functional and histological findings and clinical course.RESULTS:There were 34 patients with D-type,19 with H-type and 14 with B/T-type AIP.Although obstructive jaundice was frequently detected in D-typepatients(88%) and H-type patients(68%),no B/T-type patients showed jaundice as an initial symptom(P < 0.001).There were no differences in frequency of abdominal pain,but acute pancreatitis was associated more frequently in B/T-type patients(36%) than in D-type patients(3%)(P = 0.017).Serum immunoglobulin G(IgG)4 levels were significantly higher in D-type patients(median 309 mg/dL) than in B/T-type patients(133.5 mg/dL)(P = 0.042).Serum amylase levels in B/T-type patients(median:114 IU/L) were significantly greater than in H-type patients(72 IU/L)(P = 0.049).Lymphoplasmacytic sclerosing pancreatitis(LPSP) was histologically confirmed in 6 D-type,7 H-type and 4 B/T-type patients;idiopathic duct-centric pancreatitis was observed in no patients.Marked fibrosis and abundant infiltration of CD20-positive B lymphocytes with few IgG4-positive plasma cells were detected in 2 B/T-type patients.Steroid therapy was effective in all 50 patients(31 D type,13 H type and 6 B/T type).Although AIP relapsed during tapering or after stopping steroids in 3 D-type and 3 H-type patients,no patients relapsed in B/T type.During follow-up,radiological features of 6 B/T-type patients were not changed and 1 B/T-type patient improved naturally.CONCLUSION:Clinical features of H-type AIP were similar to those of D-type,but B/T-type differed from D and H types.B/T-type may involve diseases other than LPSP.

Utility of pancreatography for diagnosing autoimmune pancreatitis

AIM: To identify pancreatographic findings that facilitate differentiating between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) on endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP). METHODS: ERCP findings of 48 AIP and 143 PC patients were compared. Diagnostic accuracies for AIP by ERCP and MRCP were compared in 30 AIP patients. RESULTS: The following ERCP findings suggested a diagnosis of AIP rather than PC. Obstruction of the main pancreatic duct (MPD) was more frequently detected in PC (P < 0.001). Skipped MPD lesions were detected only in AIP (P < 0.001). Side branch derivation from the narrowed MPD was more frequent in AIP (P < 0.001). The narrowed MPD was longer in AIP (P < 0.001), and a narrowed MPD longer than 3 cm was more frequent in AIP (P < 0.001). Maximal diameter of the upstream MPD was smaller in AIP (P < 0.001), and upstream dilatation of the MPD less than 5 mm was more frequent in AIP (P < 0.001). Stenosis of the lower bile duct was smooth in 87% of AIP and irregular in 65% of PC patients (P < 0.001). Stenosis of the intrahepatic or hilar bile duct was detected only in AIP (P = 0.001). On MRCP, diffuse narrowing of the MPD on ERCP was shown as a skipped non-visualized lesion in 50% and faint visualization in 19%, but segmental narrowing of the MPD was visualized faintly in only 14%. CONCLUSION: Several ERCP findings are useful for differentiating AIP from PC. Although MRCP cannot replace ERCP for the diagnostic evaluation of AIP, some MRCP findings support the diagnosis of AIP.