Kensuke Takuma

Differentiation of autoimmune pancreatitis from pancreatic cancer by diffusion-weighted MRI.

OBJECTIVES:We sought to clarify the clinical utility of diffusion-weighted magnetic resonance imaging (DWI) for differentiating autoimmune pancreatitis (AIP) from pancreatic cancer.METHODS:Thirteen AIP patients underwent DWI before therapy, and six of them underwent DWI after steroid therapy. The extent and shape of high-intensity areas were compared with those of 40 pancreatic cancer patients. Apparent diffusion coefficient (ADC) values were calculated in the AIP area before and after steroid therapy in pancreatic cancer patients and in a normal pancreatic body.RESULTS:On DWI, AIP and pancreatic cancer were detected as high-signal intensity areas. The high-intensity areas were diffuse (n=4), solitary (n=6), and multiple (n=3) in AIP patients, but all pancreatic cancer patients showed solitary areas (P<0.001). A nodular shape was significantly more frequent in pancreatic cancer, and a longitudinal shape was more frequently found in AIP (P=0.005). ADC values were significantly lower in AIP (1.012±0.112 × 10−3 mm2/s) than in pancreatic cancer (1.249±0.113 × 10−3 mm2/s) and normal pancreas (1.491±0.162 × 10−3 mm2/s) (P<0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.075 × 10−3 mm2/s to distinguish AIP from pancreatic cancer. After steroid therapy, high-intensity areas on DWI disappeared or were markedly decreased, and the ADC values of the reduced pancreatic lesions increased almost to the values of normal pancreas.CONCLUSIONS:DWI is useful for detecting AIP and for evaluating the effect of steroid therapy. ADC values were significantly lower in AIP than in pancreatic cancer. An ADC cutoff value may be useful for distinguishing AIP from pancreatic cancer.

Serum IgG4 concentrations and IgG4-related sclerosing disease

BACKGROUND Based on histological and immunohistochemical examinations of various organs of patients with autoimmune pancreatitis (AIP), a new clinicopathological entity, IgG4-related systemic disease, was proposed. This study aimed to clarify clinical utility of serum IgG4 levels in differentiating AIP from other pancreatobiliary diseases, clinical utility of serum IgG4 levels in differentiating Mikuliczs disease from other salivary gland disorders, as well as in identifying other IgG4-related diseases. METHODS Serum IgG4 levels were measured in 468 patients. RESULTS The median serum IgG4 level was significantly greater in AIP (301.5mg/dl) than in other pancreatobiliary diseases (p<0.01). Using the cutoff value of 119 mg/dl that was determined on the basis of this studys ROC curve data, the sensitivity and specificity to distinguish AIP from pancreatic cancer were 82.1% and 94.8%, respectively. The median serum IgG4 level was significantly greater in Mikuliczs disease (357.0mg/dl) than in other salivary gland diseases (p<0.01). Of 75 patients with elevated serum IgG4 levels, 15 had diseases other than pancreatobiliary and salivary gland diseases. CONCLUSIONS Serum IgG4 levels were useful for diagnosing AIP and Mikuliczs disease. Some diseases with serum IgG4 level elevations may be lesions of IgG4-related systemic disease without manifestations of AIP and Mikuliczs disease.

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.

Predictors of malignancy and natural history of main-duct intraductal papillary mucinous neoplasms of the pancreas.

Objectives: Because the prevalence of carcinoma is high in main-duct intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, surgical resection is recommended for all main-duct type IPMNs. This study aimed to investigate the clinical predictors of malignancy and natural history of main-duct IPMNs. Methods: Preoperative clinical characteristics reliably correlated with malignancy in 26 surgically resected patients with main-duct IPMN, and long-term outcome in 20 conservatively followed patients with main-duct IPMN was examined. Results: Age at diagnosis was significantly older in conservatively followed IPMN patients than in surgically resected IPMN patients. Main pancreatic duct (MPD) dilatation 10 mm or greater and mural nodules were significantly more frequent in malignant IPMNs. Obvious progression of dilatation of the MPD was detected in all 4 conservatively followed patients who developed invasive pancreatic carcinoma. The histology of IPMN at autopsy of 4 conservatively followed patients who died of other causes 21 to 120 months later was adenoma. Seven conservatively followed without malignant findings did not show obvious progression of MPD dilatation. Conclusions: Although surgical resection is indicated for many main-duct IPMNs, conservative follow-up may be an option for elderly asymptomatic patients with main-duct IPMNs with the MPD less than 10 mm, no obvious mural nodule, and negative cytology.

Autoimmune pancreatitis and Igg4-related sclerosing cholangitis

Purpose of reviewAutoimmune pancreatitis (AIP) is a peculiar type of pancreatitis with a presumed autoimmune etiology. AIP is frequently associated with stenosis of the bile duct in the form of IgG4-related sclerosing cholangitis. This article reviews recent advances in clinicopathological findings for AIP and IgG4-related sclerosing cholangitis. Recent findingsAIP is currently diagnosed based on characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevated serum IgG4 and presence of autoantibodies) and histopathological findings (dense infiltration of IgG4-positive plasma cells and lymphocytes with fibrosis and obliterative phlebitis in the pancreas). Other clinical characteristics include preponderance toward elderly men, common initial symptoms of obstructive jaundice, and favorable response to steroid therapy. Differentiation of AIP from pancreatic cancer is crucial. As AIP is frequently associated with various sclerosing extrapancreatic lesions showing the same peculiar histological findings seen in the pancreas, AIP is currently considered to represent a pancreatic manifestation of IgG4-related sclerosing disease. Considering the age of onset, associated diseases, cholangiography, serum IgG4 levels, and steroid responsiveness, IgG4-related sclerosing cholangitis differs from primary sclerosing cholangitis. SummaryAIP and associated extrapancreatic lesions are considered to represent clinical manifestations of IgG4-related sclerosing disease.

Juxtapapillary Duodenal Diverticula and Pancreatobiliary Disease

Juxtapapillary duodenal diverticula (JPD) are observed in around 10–20% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). They are acquired extraluminal outpouchings of the duodenal wall through ‘locus minoris resistance’ and their incidence increases with age. They have been studied mainly with regard to their association with pancreatobiliary disease. Choledocholithiasis is considered to be strongly associated with JPD, but the role of JPD in the development of cholecystolithiasis and pancreatitis is still disputable. Since JPD are located in the vicinity of the papilla of Vater, they not only cause mechanical compression of the bile duct but also induce dysfunction of the sphincter of Oddi. They are considered to lead to bile stasis and to allow reflux from the duodenum into the bile duct, which results in an ascending infection of β-glucuronidase-producing bacteria. The ERCP procedure can be hampered by JPD, although recent papers have reported no difference in the successful cannulation rate or complications between patients with JPD and those without JPD. Disorders caused by JPD are amenable to appropriate therapy, e.g. endoscopic sphincterotomy and surgical intervention.

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.

Etiology of recurrent acute pancreatitis, with special emphasis on pancreaticobiliary malformation

PURPOSE This study was aimed to investigate etiology and clinical profiles of recurrent acute pancreatitis (RAP), particularly from the morphology of the pancreaticobiliary duct system. MATERIAL AND METHODS Pancreaticobiliary morphology was examined in 230 of 381 patients with acute pancreatitis (AP) using endoscopic retrograde cholangiopancreatography. We analyzed factors associated with RAP including the pancreaticobiliary duct system. RESULTS RAP was diagnosed in 74 patients (19%). Major etiologies of RAP were alcoholic (38%), idiopathic (26%) and pancreaticobiliary malformation (22%). Patients with alcoholic RAP were significantly younger (47.2±11.6 years) than those with gallstone RAP (67.3±16.8; p<0.05). RAP with pancreaticobiliary malformation (male-to-female ratio: 1:4.3; p<0.01) and gallstone RAP (1:1.7; p<0.05) occurred predominantly in females in comparison with alcoholic RAP (1:0.2). Recurrence rate was 80% for AP with pancreaticobiliary malformation, significantly higher than for the others (p<0.01). Pancreas divisum was suspected as the etiology of mild RAP in 7 patients. Four RAP patients with pancreas divisum underwent endoscopic minor papilla sphincterotomy and improved. Pancreaticobiliary maljunction with biliary dilatation (choledochal cyst) was suspected as the etiology of mild RAP in 3 patients. The 3 RAP patients with choledochal cyst underwent prophylactic flow diversion surgery with complete resection of the dilated common bile duct, and achieved improvement. High confluence of pancreaticobiliary ducts was suspected as the etiology of mild RAP in 6 patients. CONCLUSION Pancreaticobiliary malformation is one of the major causes of RAP. As some of them benefit from endoscopic or surgical treatment, morphology of the pancreaticobiliary duct system should be examined where possible in RAP patients.

Pancreatic diseases associated with pancreas divisum.

Aim: To clarify the features of acute or chronic pancreatitis and pancreatic tumors associated with complete and incomplete pancreas divisum. Methods: Clinical features of pancreatic diseases associated with complete (n = 54) and incomplete (n = 50) pancreas divisum were examined. Results: Acute and chronic pancreatitis occurred more frequently in patients with complete pancreas divisum (22.2%: 12/54, and 18.5%: 10/54, respectively) than in controls (5.6%: 183/3,246, and 4.9%: 159/3,246, respectively; p < 0.01). In 8 patients with chronic pancreatitis, the dorsal pancreatic duct was irregularly dilated from the orifice to the tail, whereas the ventral pancreatic duct was not dilated (isolated dorsal pancreatitis). None of the 12 complete pancreas divisum patients with acute pancreatitis consumed heavy or moderate amounts of alcohol. Although 6 of 10 patients with chronic pancreatitis consumed heavy or moderate amounts of alcohol, 31 of 32 patients with this malformation who did not exhibit pancreatitis consumed little or no alcohol. Chronic pancreatitis occurred more frequently in patients with incomplete pancreas divisum (18.0%: 9/50) than in controls (4.9%: 159/3,246; p < 0.01). Of 54 patients with complete pancreas divisum, 6 patients (11.1%) were associated with pancreatic tumor. All tumors developed from the dorsal pancreas of pancreas divisum. Conclusions: Complete pancreas divisum can be the sole etiology of acute or chronic pancreatitis. The presence of another factor, such as alcohol abuse, may be required for chronic pancreatitis to develop in some patients with complete or incomplete pancreas divisum. In complete pancreas divisum, the dorsal pancreatic duct might be a factor that promotes oncogenesis.

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.