Short and long-term outcomes of diabetes mellitus in patients with autoimmune pancreatitis after steroid therapy.

BACKGROUND/AIMS: Autoimmune pancreatitis (AIP) is frequently associated with diabetes mellitus (DM). This study evaluated the effect of steroid therapy on the course of DM in AIP. METHODS: Glucose tolerance was examined in 69 patients with AIP. DM onset was classified as either a simultaneous onset with AIP or an exacerbation of pre-existing DM. Based on the changes in the HbA1c levels and insulin dose, the responses of DM to steroids were classified as improved, no change, or worsened. RESULTS: Thirty (46%) patients were diagnosed as having DM (simultaneous onset, n=17; pre-existing, n=13). Three months after starting the steroid treatment, the DM improved in 13 (54%) of 24 DM patients. The DM improved in 55%, had no change in 36%, and worsened in 9% of the 11 simultaneous onset DM patients, and it improved in 54%, had no change in 31%, and worsened in 15% of the 13 pre-existing DM patients. At approximately 3 years after starting the steroid treatment, the DM improved in 10 (63%) of 16 patients. The pancreatic exocrine function improved in parallel with the changes in the DM in seven patients. CONCLUSIONS: Because approximately 60% of DM associated with AIP is responsive to steroids in the short- and long-terms, marked DM associated with AIP appears to be an indication for steroid therapy.

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-type patients (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.

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 enhancement 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.

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.

Management strategies for autoimmune pancreatitis.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. AREAS COVERED: The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. EXPERT OPINION: AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.

Short-term and long-term outcomes of autoimmune pancreatitis.

OBJECTIVE: To examine the short-term and long-term clinical courses of patients with autoimmune pancreatitis (AIP) who underwent different treatments and identify predictive factors for relapse of AIP after steroid therapy. METHODS: Clinical courses of 50 AIP patients followed up for more than 1 year (median 40 months, range: 12-173 months) were examined. Patients were subdivided according to initial treatments as follows: surgical procedures in 10 patients, supportive therapy in 11 patients, and steroid therapy in 29 patients. RESULTS: Of the surgically treated patients, two underwent steroid therapy later because of progressive extensive lymphadenopathy and retroperitoneal fibrosis, respectively. Five conservatively followed-up patients were later given steroid therapy because of exacerbation of AIP involving the bile duct. Steroid therapy was effective in all patients. Pancreatic endocrine and exocrine dysfunctions and salivary gland dysfunction improved after steroid therapy in 100, 85, and 75% of patients, respectively. AIP relapsed in five patients initially treated with steroid, and presence of hilar bile duct stenosis and elevated serum IgG4 levels were significantly associated with relapse. Two relapsed AIP patients developed a pancreatic stone 2 and 3 years later. Although seven patients died, no patient died of AIP-related diseases or developed pancreatic carcinoma. CONCLUSION: Most AIP patients treated with steroid had good short-term and long-term outcomes clinically, morphologically, and functionally. Hilar bile duct stenosis and elevated serum IgG4 levels were predictors of AIP relapse after steroid therapy. As some patients developed pancreatic stone formation or a malignancy during or after steroid therapy, AIP patients should be rigorously followed up.

Serum IgG4-negative autoimmune pancreatitis.

BACKGROUND: Autoimmune pancreatitis (AIP) is considered to be a pancreatic lesion of IgG4-related systemic disease, but about 20% of AIP patients do not have elevated serum IgG4 levels. This study aimed to clarify the pathophysiology of AIP patients without elevated serum IgG4 levels. METHODS: Fifty-eight AIP patients were divided into 2 groups: those with elevated serum IgG4 levels (>135 mg/dl; SIgG4-positive AIP) and those without (SIgG4-negative AIP). The 2 groups' clinical, serological, radiological, and histological findings, as well as salivary and lacrimal gland function, were compared. RESULTS: Serum IgG4 levels were elevated in 45 AIP patients and normal in 13 patients. In SIgG4-negative AIP patients, the female ratio tended to be high; obstructive jaundice was less likely; abdominal pain and acute pancreatitis were more likely; segmental swelling of the pancreatic body and/or tail was more common; sclerosing extrapancreatic lesions, salivary and lacrimal gland dysfunction, and abundant infiltration of IgG4-positive plasma cells in the gastric mucosa were less likely; and conservative follow-up was sometimes implemented. Histological examination of the pancreas of SIgG4-negative AIP showed lymphoplasmacytic sclerosing pancreatitis (LPSP) rather confined to the pancreas (n = 4), inadequate material (n = 2), and pancreatic fibrosis showing infiltration of lymphocytes without infiltration of IgG4-positive cells or neutrophils (n = 2). CONCLUSIONS: Clinicopathological features of SIgG4-negative AIP differed from those of SIgG4-positive AIP. Some SIgG4-negative AIP cases are LPSP rather confined to the pancreas. SIgG4-negative AIP may include idiopathic duct-centric pancreatitis (IDCP) or sclerosing pancreatitis other than LPSP or IDCP, but further studies are needed to clarify this issue.