Junko Fujiwara

Multi‐center survey regarding the management of anticoagulation and antiplatelet therapy for endoscopic procedures in Japan

Background:  A guideline on the management of anticoagulation and antiplatelet therapy for endoscopic procedures has been established from Japan Gastroenterological Endoscopy Society in 2005. However, it is unknown whether consensus on the management of these conditions is obtained among endoscopists in daily practice owing to the guideline.

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.

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: A coincidental association

BACKGROUND/AIMS Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. METHODS Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. RESULTS Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. CONCLUSIONS In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.

Differentiating Immunoglobulin G4-Related Sclerosing Cholangitis from Hilar Cholangiocarcinoma

Background/Aims Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. Methods We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. Results In patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01). Conclusions An integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC.

Clinical Characteristics of Patients with Autoimmune Pancreatitis with or without Mikulicz's Disease and Mikulicz's Disease Alone

Background/Aims The objective of this study was to compare the clinical characteristics of patients with autoimmune pancreatitis (AIP) with or without Mikuliczs disease (MD) and with MD alone. Methods We investigated the clinical findings in 15 AIP patients with MD (group A+M), 49 AIP only patients (group A), and 14 MD only patients (group M). Results The male-female ratio was significantly higher in group A+M (73%, p<0.05) and group A (78%, p<0.01) than group M (21%). Serum immunoglobulin G (IgG) levels were significantly higher in group A+M than in group A (p<0.01) and group M (p<0.05). Serum IgG4 levels were significantly higher in group A+M than in group A (p<0.01). Other organ involvement was observed in 73% (11/15) of patients in group A+M. The number of patients with diabetes mellitus was significantly higher in group A+M (66%, p<0.01) and group A (51%, p<0.05) than in group M (7%). All of the patients responded well to steroid therapy, but the relapse rate in group A+M (33%) was significantly higher than that in group A (3%, p<0.01). Salivary gland function was impaired in all groups compared with the control group, but the degree of dysfunction was less in group A compared with group A+M and group M. Conclusions The relapse rate of AIP in MD patients was significantly higher than that of AIP in patients without MD.

Organ Correlation in IgG4-Related Diseases

IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs. Graphical Abstract

Ulcerative Colitis and Immunoglobulin G4

Background/Aims Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). Conclusions UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.

Capability and limitations of recent diagnostic criteria for autoimmune pancreatitis.

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC.

Embryological aspects in autoimmune pancreatitis, proposal of autoimmune dorsal pancreatitis.

Abstract Objective. We examined the anatomy of the pancreatic duct system in patients with autoimmune pancreatitis (AIP) from the standpoint of embryological pancreatic primordial. Material and methods. The pancreatic duct system involved in 83 AIP patients was embryologically divided into both ventral and dorsal pancreatic ducts (VD type), only the dorsal pancreatic duct (D type), or only the ventral pancreatic duct (V type). Results. The 83 AIP patients were divided into 62 VD type, 20 D type, and 1 V type. Obstructive jaundice was significantly more frequent in VD type (87%) than in D type (0%; p < 0.01), and abdominal pain was more frequent in D type (24%) than in VD type (2%; p < 0.01). Stenosis of the lower bile duct was detected in 98% of VD type and 15% of D type (p < 0.01). In the 67 patients with involvement of the pancreatic head, only the dorsal pancreatic duct was involved with a normal ventral pancreatic duct in four patients (D type). In the four D-type patients, the pancreatic duct system showed complete pancreas divisum (n = 1), incomplete pancreas divisum (n = 2), or normal pancreatic duct system (n = 1). Stenosis of the lower bile duct was seen in three patients, but was mild, resulting in no obstructive jaundice. Three patients reported abdominal pain and one patient developed acute pancreatitis. Conclusions. We propose a new entity of “autoimmune dorsal pancreatitis” in which only the dorsal pancreas is involved, and involvement of the lower bile duct and obstructive jaundice is rare.

DOES A PATENT ACCESSORY PANCREATIC DUCT PREVENT ACUTE PANCREATITIS

Background and Aim:  The role of the accessory pancreatic duct (APD) in pancreatic pathophysiology has been unclear. We previously examined the patency of the APD in 291 control cases who had a normal pancreatogram in the head of the pancreas by dye‐injection endoscopic retrograde pancreatography (ERP). APD patency was 43% and was closely related with the shape of the terminal portion of the APD. The present study aimed to clarify the clinical implications of a patent APD.