Hirotaka Ohara

Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal.

In 1961, Sarles et al.1 asked the following question regarding the particular cases of pancreatitis with hypergammaglobulinemia: “Chronic inflammatory sclerosis of the pancreas—an autoimmune pancreatic disease?” As similar cases were rarely observed, a relationship between such pancreatitis and autoimmunity was viewed skeptically during the following several decades. In 1992, Toki et al.2 have reported 4 cases with unusual diffuse irregular narrowing of the main pancreatic duct and diffuse enlargement of the entire pancreas due to lymphocyte infiltration. In 1995, Japanese investigators3 firstly proposed a concept of “autoimmune pancreatitis (AIP)”, in which the patients showed diffusely enlarged pancreas, narrowing pancreatogram, increased serum IgG, presence of autoantibodies, fibrotic changes with lymphocytic infiltration and steroidal efficacy. Thereafter, many AIP cases have been reported from Japan, and AIP has been accepted as a new clinical entity.4,5 The histopathological findings of AIP show massive infiltration of lymphoplasmacytes with fibrosis, which is consistent with lymphoplasmacytic sclerosing pancreatitis (LPSP).6 Many Japanese investigators have paid great attention to AIP, especially with regard to its unique pancreatic images,2 IgG4,7 disease-associated autoantibodies,8 extrapancreatic lesions,6,9–14 and steroidal efficacy.14,15 Currently in Japan, diagnosis of AIP is based on the “diagnostic criteria 2002 of autoimmune pancreatitis”16 proposed by the Japan Pancreas Society. However, the accumulation of many AIP cases shows that the concept of AIP has changed slightly to include extrapancreatic lesions and associated disorders, which suggests that the current diagnostic criteria are becoming inadequate. In 2003, the Research Committee of Intractable Diseases of the Pancreas, supported by the Japanese Ministry of Health, Labour and Welfare (Chairman, M. Otsuki), began to review the current diagnostic criteria in light of recently acquired information and knowledge. The team organized a working group (WG), consisting of the team members and researchers specializing in autoimmune pancreatitis, to develop a proposal for the revision of the current diagnostic criteria. On 7 October 2005 and 22 April 2006, the Research Committee of Intractable Diseases of the Pancreas and the Japan Pancreas Society jointly held open forums to discuss the proposed amendments. This report describes the background of the proposed amendments and the final proposal for the revised version of the clinical diagnostic criteria of AIP.

International consensus guidance statement on the management and treatment of IgG4-related disease

A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone

Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis

BACKGROUND Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis. METHODS Cholangiograms from patients with primary sclerosing cholangitis (n = 29) and sclerosing cholangitis with autoimmune pancreatitis (n = 26) were studied with regard to length and region of stricture formation, and other characteristic findings. RESULTS Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis. CONCLUSIONS Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.

Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012

BackgroundIgG4-sclerosing cholangitis (IgG4-SC) patients have an increased level of serum IgG4, dense infiltration of IgG4-positive plasma cells with extensive fibrosis in the bile duct wall, and a good response to steroid therapy. However, it is not easy to distinguish IgG4-SC from primary sclerosing cholangitis, pancreatic cancer, and cholangiocarcinoma on the basis of cholangiographic findings alone because various cholangiographic features of IgG4-SC are similar to those of the above progressive or malignant diseases.MethodsThe Research Committee of IgG4-related Diseases and the Research Committee of Intractable Diseases of Liver and Biliary Tract in association with the Ministry of Health, Labor and Welfare, Japan and the Japan Biliary Association have set up a working group consisting of researchers specializing in IgG4-SC, and established the new clinical diagnostic criteria of IgG4-SC 2012.ResultsThe diagnosis of IgG4-SC is based on the combination of the following 4 criteria: (1) characteristic biliary imaging findings, (2) elevation of serum IgG4 concentrations, (3) the coexistence of IgG4-related diseases except those of the biliary tract, and (4) characteristic histopathological features. Furthermore, the effectiveness of steroid therapy is an optional extra diagnostic criterion to confirm accurate diagnosis of IgG4-SC.ConclusionThese diagnostic criteria for IgG4-SC are useful in practice for general physicians and other nonspecialists.

Japanese clinical guidelines for autoimmune pancreatitis.

Objectives: As the patients with autoimmune pancreatitis (AIP) are increasing in Japan, the practical guideline for managing AIP is required to be established. Methods: Three committees (the professional committee for making clinical questions [CQs] and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Fifteen specialists for AIP extracted the specific clinical statements from a total of 871 literatures by PubMed search (∼1963-2008) and from a secondary database and made the CQs and statements. The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. Results: The professional committee made 13, 6, 6, and 11 CQs and statements for the concept and diagnosis, extrapancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. Conclusions: After evaluation by the moderators, the Japanese clinical guideline for AIP has been established. Further studies for the international guideline are needed after international consensus for diagnosis and treatment.

Unilateral versus bilateral endoscopic metal stenting for malignant hilar biliary obstruction.

Background and Aim:  The extent of liver drainage for palliative treatment of malignant hilar biliary obstruction is controversial. The aim of this study was to compare endoscopic unilateral versus bilateral drainage in patients with malignant hilar biliary obstruction using a self‐expanding metal stent (SEMS).

Immunohistochemical study of autoimmune pancreatitis using anti-IgG4 antibody and patients' sera

Aims : Autoimmune pancreatitis (AIP), characterized by raised serum IgG4 levels, is frequently complicated by disorders of extrapancreatic organs. The aim of the present study was to examine immunohistochemically which extrapancreatic organs are affected, and whether an autoantibody to such organs is present in the serum of AIP patients.

Th1/Th2 cytokine profiles and their relationship to clinical features in patients with chronic hepatitis C virus infection

Purpose. An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is suggested to play an important role in the pathogenesis of chronic viral infections, but this issue is not resolved in patients with hepatitis C virus (HCV) infection. The aim of this study was to clarify the relationship between the balance of Th1 and Th2 cytokines and liver damage. Methods. We investigated cytokine levels in the peripheral blood and liver tissue of patients with chronic HCV infection (n = 59) by three different methods; we used flow cytometry to detect intracellular cytokines, and we measured cytokine titers in sera and in the supernatants of lymphocyte cultures with enzyme-linked immunosorbent assays (ELISAs). Results. In both CD4+ and CD8+ cells, interferon (IFN) γ-producing cell populations increased, while there was no difference in interleukin (IL)-10 production, indicating a shift to a Th1 cytokine profile with the progression of liver disease. With respect to the ratio of IFN-γ to IL-10, a correlation was found in CD4+ cells between peripheral blood and liver tissue (r = 0.98; P = 0.0011). Th1 cytokine was predominant in intrahepatic CD4+ cells, while it was predominant in peripheral blood CD8+ cells. Conclusions. These findings indicate a correlation between dominant Th1 response and disease activity and progression. In addition, we suggest that intrahepatic CD4+ T cells play a pathogenetic role in the hepatic injury of HCV infection.

Interleukin-6 is a useful marker for early prediction of the severity of acute pancreatitis.

Twelve patients with acute pancreatitis admitted to our department between January 1993 and December 1994 were studied prospectively and classified into two groups (severe group, five patients; mild group, seven patients), according to the criteria for grading severity of acute pancreatitis proposed by the Research Committee for Intractable Diseases of the Pancreas, Japanese Ministry of Health and Welfare (1990). To evaluate markers for early estimation of the severity of acute pancreatitis, we measured serum changes in various parameters. In the severe group interleukin-6 (IL-6) levels were increased significantly 5, 24, 72, and 120 h after the onset (p < 0.01), compared with the mild group. C-reactive protein (CRP), thrombin antithrombin III, and α2-plasmin inhibitor plasmin complex levels were significantly increased only at the 72-h time point. Peak values of interleukin-8 (IL-8) and soluble human E selectin were observed at 5 and 72 h, respectively, after the onset. There was a significant correlation between IL-6 at 5 h and both pancreatic secretory trypsin inhibitor (r = 0.85) and CRP (r = 0.94) at 72 h. We therefore conclude that IL-6 is a useful marker for assessment of the severity of acute pancreatitis in its early stages.

The revised Japanese clinical diagnostic criteria for chronic pancreatitis

In Japan, we are now using the clinical diagnostic criteria for chronic pancreatitis (CP) that were revised in 2001 to add the findings of magnetic resonance cholangiopancreatography to the criteria compiled by the Japan Pancreas Society (JPS) in 1995. Because the current criteria are set for diagnosing advanced CP, they are unlikely to improve patients’ prognoses. In addition, they seem unsuitable for current clinical practice because exocrine pancreatic function tests, which have become obsolete in Japan, are included in the diagnostic factors. For these reasons, the Research Committee on Intractable Pancreatic Diseases supported by the Ministry of Health, Labour and Welfare of Japan, the JPS and the Japanese Society of Gastroenterology have revised the criteria. The revised criteria are unique in that they contain an introduction to the concept of early CP. It is a challenge aimed at improvement of the long-term prognosis of CP patients by early diagnosis and therapeutic intervention in this disease. We need to determine and clarify the clinico-pathological outcome of early CP by a prospective long-term follow-up of the patients in this category.