Mari Takayama

Recurrent attacks of autoimmune pancreatitis result in pancreatic stone formation.

OBJECTIVES:Autoimmune pancreatitis has been characterized by irregular narrowing of the main pancreatic duct and sonolucent swelling of the parenchyma, both of which are due to lymphoplasmacytic inflammation at the active stage of the disease, and by the absence of pancreatic stone formation. The aim of the present study was to confirm or deny whether or not this disease is progressive with recurrent attacks, resulting in pancreatic stone formation like ordinary chronic pancreatitis.METHODS:Forty-two patients, 36 of whom were treated with prednisolone, were followed up for periods longer than 12 months (median follow-up period: 54.5 months, range: 13–111 months) by regular interview and examination of their medical records for laboratory tests and image tests.RESULTS:Eleven patients (26.2%) who were treated with prednisolone showed recurrent attacks during median follow-up periods of 22 months. Eight patients (19%) showed the formation of pancreatic stones during the follow-up periods. Because 6 of 11 patients (54.5%) who suffered relapse showed pancreatic stone formation, it is significantly associated with relapse in comparison with nonrelapse (p = 0.0019).CONCLUSIONS:Contrary to previous reports, we observed both relapse and pancreatic stone formation in some patients with autoimmune pancreatitis, which suggests that autoimmune pancreatitis has the potential to be a progressive disease with pancreatic stones.

Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma : part of a spectrum of autoimmune pancreatitis?

BACKGROUND Autoimmune pancreatitis has been designated as sclerosing pancreatocholangitis, because this disease shows a high prevalence of bile-duct lesions. We present herein the clinical characteristics of unusual cases that show dominant bile-duct lesions and mimicking infiltrating hilar cholangiocarcinomas. METHODS Clinical and pathologic findings of 3 patients with immunoglobulin (Ig) G4 related sclerosing cholangitis who had no apparent pancreatic lesions comparable with autoimmune pancreatitis were analyzed. OBSERVATIONS All patients were middle-aged or elderly individuals with slightly elevated serum IgG4 concentrations and showed long-segment narrowing of the bile-duct system, mimicking infiltrating hilar cholangiocarcinoma without significant pancreatic change. The first patient was treated with a corticosteroid, resulting in amelioration of the narrowing of the bile duct. The second patient underwent surgery based on a diagnosis of cholangiocarcinoma. In the third patient, the bile-duct stricture reversed spontaneously 1 month after the drainage procedure. Pathologic findings of the bile ducts for all patients disclosed significant lymphoplasmacytic infiltration, including abundant IgG4-bearing plasma cells. CONCLUSIONS The use of IgG4 immunostaining in biopsy specimens of the bile duct may identify the presence of corticosteroid-responsive lymphoplasmacytic sclerosing cholangitis.

High prevalence of hypothyroidism in patients with autoimmune pancreatitis.

Autoimmune pancreatitis is a unique form of chronic pancreatitis and has been correlated with various extrapancreatic lesions. To search for a correlation between autoimmune pancreatitis and thyroid lesions, we measured thyroid functions in 41 patients with autoimmune pancreatitis and in 41 patients with chronic calcifying pancreatitis and investigated the correlation between HLA antigens and hypothyroidism. We found a significant difference in the prevalence of antithyroglobulin antibody and hypothyroidism between patients with autoimmune pancreatitis and those with chronic pancreatitis (34.1 vs. 7.3%, P = 0.005, and 26.8 vs. 0%, P = 0.0005, respectively). Patients with hypothyroidism had a significantly higher frequency of antithyroglobulin antibody (63.6%) than those without hypothyroidism but showed no differences in other findings, including serum IgG4 concentration. We could find no significant association between any HLA antigens and the hypothyroid state of autoimmune pancreatitis. One quarter of the patients with autoimmune pancreatitis have hypothyroidism that may be independent of the active state of the pancreatic lesion or systemic fibrosing disorder, and thus patients suspected of having autoimmune pancreatitis should be evaluated for possible hypothyroidism.

Hilar and Pancreatic Gallium-67 Accumulation is Characteristic Feature of Autoimmune Pancreatitis

Introduction and Aims Autoimmune pancreatitis is characterized by severe lymphocytic inflammation, suggesting that gallium-67 scintigraphy provides a useful tool for detecting characteristic lesions of this disease, because gallium-67 concentrates in lymphoid cells. We tried to determine whether gallium-67 accumulates in the characteristic lesions. Methodology We performed gallium-67 scintigraphy in 24 patients with autoimmune pancreatitis before and after 4 weeks of corticosteroid therapy and determined the factors associated with positive images. Results Sixteen patients (67%) had marked gallium-67 accumulation in the pancreas before corticosteroid therapy and negative images after 4 weeks of therapy, and they had significantly higher serum IgG4 values than did those without gallium-67 accumulation (median, 758 mg/dL versus 329 mg/dL; p = 0.011). Marked hilar gallium-67 accumulation was found in 16 patients (67%) and was also associated with significantly higher serum IgG4 values than did those without it (median, 758 versus 239 mg/dL; p = 0.0044). Among 16 patients with positive hilar images, 12 had positive pancreatic uptake and 5 had both pancreatic and salivary gland uptakes. Conclusions Hilar and pancreatic accumulation of gallium-67 is a characteristic feature of autoimmune pancreatitis during the active stage of the disease, when IgG4 serum levels are high.

Long-Term Follow-Up of Autoimmune Pancreatitis: Characteristics of Chronic Disease and Recurrence

Autoimmune pancreatitis is a unique disease, characterized by lymphoplasmacytic inflammation in the acute stages. However, the active clinical features are unlikely to persist for long periods. Through long-term follow-up, we investigated the disease course in 51 patients with autoimmune pancreatitis. We found recurrence in 21 (41%) patients and pancreatic stone formation in 9 (18%) patients. Pancreatic stone formation was significantly more frequent in the recurrence group (7/21, 33%), compared with the nonrecurrence group (2/30, 7%). Moreover, we found high serum immunoglobulin G4 concentrations in 13 of 175 (7.4%) patients with ordinary chronic pancreatitis. This suggested that pancreatic stone formation is closely associated with recurrence and that autoimmune pancreatitis might transform into ordinary chronic pancreatitis after several recurrences. We found that the immune complex level, with a cutoff value of 10 microg/dL, served as a good predictor of recurrence, with high sensitivity (61.9%), specificity (70.0%), and efficacy (66.7%). We also confirmed that HLA and cytotoxic T-lymphocyte antigen-4 polymorphisms were useful predictors for AIP recurrence.

Efficacy of preoperative endoscopic nasobiliary drainage for hilar cholangiocarcinoma

BACKGROUND/PURPOSE Although percutaneous transhepatic biliary drainage has previously been recommended as a primary preoperative step, endoscopic nasobiliary drainage (ENBD) is prevalent as an alternative procedure. Few reports assess the efficacy and safety of ENBD in a substantial patient cohort. METHODS Of 116 patients with hilar cholangiocarcinoma who underwent surgery, 62 (43 men and 19 women, median age 69 years) underwent preoperative ENBD. After classification of lesions according to Bismuth-Corlette (B-C) criteria, we evaluated efficacy and safety with respect to B-C type. RESULTS Patients were classified as B-C types I (n = 5), II (n = 21), IIIa (n = 23), IIIb (n = 5), and IV (n = 8). Preoperative single ENBD was effective in 46/62 patients (74%) including 5/5 (100%) B-C type I, 20/21 (94%) type II, 16/23 (70%) type IIIa, 4/5 (80%) type IIIb, and 1/8 (13%) type IV. Sixteen cases (26%) required additional drainages with ENBD or endoscopic biliary stenting (EBS) in 8/16 (50%), and with PTBD in 8/16 (50%). Mild acute pancreatitis (n = 1, 2%), segmental cholangitis (n = 2, 3%), and acute cholangitis with catheter obstruction (n = 7, 11%) occurred with ENBD. CONCLUSIONS Preoperative single ENBD in the future remnant lobe is effective treatment for B-C type I-III hilar cholangiocarcinoma. Preoperative ENBD was rarely complicated with segmental cholangitis.

Corticosteroid-responsive pancreatic cyst found in autoimmune pancreatitis

There have been only a few reports of autoimmune pancreatitis complicated with pancreatic cyst and such cysts are rare, probably due to the absence of severe tissue necrosis and/or lack of stasis of the pancreatic juice in this condition. However, during a follow-up of 48 patients with this disease, we found 3 patients with pancreatic cysts, and this enabled us to evaluate their clinicopathological findings. Between September 1994 and July 2003, we treated and followed 48 patients with autoimmune pancreatitis, and found 3 patients with pancreatic cyst formation that was responsive to corticosteroid therapy. All of the patients with cysts had high serum IgG4 concentrations. After corticosteroid therapy, rapid resolution of the pancreatic cysts was observed. Immunostaining with goat polyclonal antibody for each IgG subclass showed severe infiltration of IgG4-positive plasma cells in the cyst wall in one patient. The high serum IgG4 concentration and favorable response to corticosteroid therapy suggests that a highly active state of the inflammatory process is closely associated with cyst formation, and that a corticosteroid-responsive pancreatic cyst is a characteristic feature of autoimmune pancreatitis.

Association analysis of Toll-like receptor 4 polymorphisms with autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is characterized by lymphoplasmocytic inflammation, high serum IgG4 concentrations, and a favorable response to corticosteroid treatment. Although long-term follow-up studies have shown that a relapse rate of 30-40% can occur in AIP after remission with corticosteroids, there are few genetic characteristic predictors of relapse in AIP patients. Toll-like receptor (TLR) is an important mediator in both innate and adaptive immunity. Polymorphisms in TLR4 gene have been linked with several autoimmune and allergic diseases. We therefore investigated the genetic association between TLR4 polymorphisms and AIP susceptibility and relapse in a Japanese population. Eight SNPs in TLR4 (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, rs11536889, rs7037117, and rs7045953) were genotyped in 59 patients with AIP and 126 healthy controls using a TaqMan assay. Analysis of allelic frequencies revealed no statistical association with either susceptibility or relapse of AIP. These data indicate that TLR4 polymorphisms do not play an important role in the development of AIP.

Microsatellite Scan Identifies New Candidate Genes for Susceptibility to Alcoholic Chronic Pancreatitis in Japanese Patients

Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years) and 99 healthy Japanese controls were enrolled in this study. This was an association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. This search revealed 10 candidate susceptibility regions and 5 candidate resistant regions throughout the genome. No specific microsatellite markers were detected in association with previously reported susceptibility genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007 on chromosome 15q14 showed strong evidence for disease susceptibility (70.8% vs. 35.1%, Pc = 0.0001). Within 500 kb of D15S1007, several genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281, LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and 5 candidate resistant regions that may contain genes involved in ACP pathogenesis.

Pancreaticobiliary fistula associated with pancreatolithiasis

We report here a case of pancreaticobiliary fistula associated with pancreatolithiasis. A 47-year-old female without a habit of alcohol drinking was admitted by her family physician after suffering from mild acute pancreatitis. Computed tomography revealed mild acute pancreatitis with pancreatolithiasis at the head of the pancreas. The pancreatolithiasis was exposed to the inner surface of the common bile duct and possibly compressed and narrowed the Wirsung and Santorini ducts, resulting in the pancreatitis attack. We used extracorporeal shock wave lithotripsy to treat the pancreatolithiasis. After complete elimination of stones by extracorporeal shock wave lithotripsy, endoscopic retrograde cholangiography showed an apparent pancreaticobiliary fistula between a branch of the Santorini duct and the lower portion of the common bile duct. There was no communication between the bile duct and the Wirsung duct or its branches; therefore, the diagnosis was not pancreaticobiliary maljunction. There have only been a few reports of pancreaticobiliary fistula without an association with pancreatic pseudocysts or intraductal papillary-mucinous pancreatic neoplasm, and there have only been few reports of pancreaticobiliary fistula with pancreatolithiasis.