Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan-Korea Symposium on Autoimmune Pancreatitis

In 2002, the Japan Pancreas Society (JPS) was the first in the world to propose diagnostic criteria for autoimmune pancreatitis (AIP). Since the concept of AIP has changed with the accumulation of AIP cases, the Research Committee of Intractable Pancreatic Diseases (RCIPD) provided by the Ministry of Health, Labour and Welfare of Japan and the JPS issued revised clinical diagnostic criteria of AIP in 2006. The Asan Medical Center of Korea also proposed diagnostic criteria for AIP in 2006. However, there are subtle but clinically challenging differences between the Japanese and Korean criteria. This inconsistency makes it difficult to compare data in studies from different centers and elucidate the characteristics of AIP. To reach a consensus on AIP, the RCIPD and the Korean Society of Pancreatobiliary Diseases established the following Asian criteria for the diagnosis of AIP: I-1. Imaging studies of pancreatic parenchyma show a diffuse/segmental/focally enlarged gland, occasionally with a mass and/or a hypoattenuation rim. I-2. Imaging studies of pancreaticobiliary ducts show diffuse/segmental/focal pancreatic ductal narrowing, often with stenosis of the bile duct. (Both I-1 and I-2 are required for diagnosis). II. Elevated level of serum IgG or IgG4, and detection of autoantibodies. III. Common lymphoplasmacytic infiltration and fibrosis, with abundant IgG4-positive cell infiltration. AIP should be diagnosed when criterion I and one of the other two criteria are satisfied, or when histology shows the presence of lymphoplasmacytic sclerosing pancreatitis in the resected pancreas. A diagnostic trial of steroid therapy can be applied carefully by expert pancreatologists only in patients fulfilling criterion I alone with negative diagnostic work-up results for pancreatobiliary cancer.     

A new clinicopathological entity of IgG4-related autoimmune disease

Background Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.Methods To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies.Results In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls.Conclusions These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.     

Pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction: a prospective multicenter study

Background

Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree.

Methods

Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy.

Results

Twenty-three patients (5.5 %) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P < 0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer.

Conclusions

The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.     

Recent advances and problems in the management of pancreaticobiliary maljunction: feedback from the guidelines committee

Clinical practice guidelines on how to deal with pancreaticobiliary maljunction (PBM) were made in Japan in 2012, representing a world first. Using a narrow definition, congenital biliary dilatation involves only Todani type I (except type Ib) and type IV‐A, both of which are accompanied by PBM in almost all cases. Prospective ultrasonographic study revealed that the maximum diameter of the common bile duct increased with age. Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of the pancreaticobiliary ducts, a common channel ≥6 mm long and occlusion of communication during contraction of the sphincter of Oddi. Since PBM can be diagnosed by magnetic resonance cholangiopancreatography, multi‐planar reconstruction multi‐detector row computed tomography and endoscopic ultrasonography, the current diagnostic criteria should be revised to take these diagnostic imaging modalities into consideration. According to a nationwide survey, biliary cancer occurred in 21.6% of adult patients with PBM with biliary dilatation and 42.2% of patients with PBM without biliary dilatation. In biliary cancer associated with PBM without biliary dilatation, 88.1% were gallbladder cancer. Treatment for PBM with biliary dilatation is prophylactic flow‐diversion surgery, but further investigations and surveillance studies are needed to clarify the appropriate surgical strategy for PBM without biliary dilatation.     

Clinical significance of the minor duodenal papilla and accessory pancreatic duct

The accessory pancreatic duct (APD) is the main drainage duct of the dorsal pancreatic bud in the embryo, entering the duodenum at the minor duodenal papilla (MIP). As development progresses, the duct of the dorsal bud undergoes varying degrees of atrophy at the duodenal end. In cases of patent APD, smooth-muscle fiber bundles derived from the duodenal proper muscular tunics surround the APD. The APD shows long and short patterns on pancreatography, and ductal fusion in the two types appears to differ embryologically. Patency of the APD in control cases, as determined by dye-injection endoscopic retrograde pancreatography, was 43%. Patency of the APD may depend on duct caliber, course, and terminal shape of the APD. A patent APD may prevent acute pancreatitis by reducing the pressure in the main pancreatic duct. Pancreas divisum is a common anatomical anomaly in which the ventral and dorsal pancreatic ducts do not unite embryologically. As the majority of exocrine flow is routed through the MIP in individuals with pancreas divisum, interrelationships between poor function of the MIP and increased flow of pancreatic juice caused by alcohol or diet may increase dorsal pancreatic duct pressure and lead to the development of pancreatitis. Wire-guided minor sphincterotomy, followed by dorsal duct stenting, is recommended for acute recurrent pancreatitis associated with pancreas divisum.     

Chronic pancreatitis progressing from segmental lesions

BACKGROUND/AIMS: Chronic pancreatitis is histologically and functionally a progressive disease. To examine the natural history of chronic pancreatitis, we evaluated serial pancreatography in cases of chronic pancreatitis, focusing on the progression of diffuse-type chronic pancreatitis from the segmental type. METHODOLOGY: We reviewed 57 patients with chronic pancreatitis who had undergone endoscopic retrograde pancreatography on more than 2 occasions at intervals of at least 1 year. Cases of chronic pancreatitis were categorized as diffuse (n=37) and segmental (n=20) on the findings of initial endoscopic retrograde pancreatography. RESULTS: Twenty-three cases of diffuse-type chronic pancreatitis showed progression of pancreatic duct abnormalities. Segmental abnormalities of the main pancreatic duct at the body or tail of the pancreas spread to the head of the pancreas in 8 cases. Etiologies of these cases of chronic pancreatitis were alcoholic, in which patients continued drinking after initial endoscopic retrograde pancreatography. In 2 patients who underwent distal pancreatectomy, although segmental lesions showed typical histological findings of alcoholic chronic pancreatitis, appearances near the margin of these lesions were almost normal or indicated slight interlobular fibrosis. CONCLUSIONS: The pancreatic tail might represent the site of the initial lesion in some cases of alcoholic pancreatitis.     

Intraoperative radiation therapy for pancreatic adenocarcinoma: the Komagome hospital experience

We analyzed 144 patients with pancreatic adenocarcinoma who had received intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) within the past 20 years. The patients were divided into 2 groups: group 1 contained 65 patients with locally unresectable tumors who underwent bypass operations and group 2 contained 68 patients with resectable tumors who underwent pancreatic resection. As a pilot study, we performed additional arterial infusion chemotherapy after changing peripancreatic hemodynamics during EBRT in the remaining 11 patients. The 30 patients who received R0 resection had the best survival rates (3-year survival rate of 35.4%), while 3 patients with stage III disease survived more than 5 years. The survival of group 1 patients nearly equaled that of group 2 patients who underwent R1 or R2 resection (median survival, 10.9 vs. 11.1 months, respectively; P = 0.43). The 1-year survival rate for the 11 patients receiving arterial infusion chemotherapy was 45.4%, and 5 patients survived over 1 year without developing hepatic metastasis or regrowth of primary tumors. The survival benefits obtained using this form of radiotherapy are apparently limited. On the other hand, additional arterial infusion chemotherapy employing a new drug delivery system using hemodynamic change does appear promising.     

The presence of a common channel and associated pancreaticobiliary diseases: A prospective ERCP study

BACKGROUND: There are few endoscopic retrograde cholangiographic studies dealing with the relationship between the presence of a common channel and associated pancreaticobiliary diseases. AIMS: To endoscopically determine the incidence of common channels and assess whether the anatomy of the pancreaticobiliary ductal drainage into the duodenum has any bearing on pancreaticobiliary diseases. PATIENTS AND METHODS: We prospectively examined a common channel formation in 354 endoscopic retrograde cholangiographic cases. Cases with a common channel were divided into three groups: pancreaticobiliary maljunction, high confluence of pancreaticobiliary ducts with a common channel > or =6 mm in which the communication was occluded with the sphincter contraction, and common channel < or =5 mm in length. RESULTS: A common channel was observed in 131 cases (37.0%) including 11 with pancreaticobiliary maljunction and 13 with high confluence of pancreaticobiliary ducts. In cases with a common channel, the incidences of associated gallbladder carcinoma and acute pancreatitis were both 11.5%, which were significantly higher than 1.8% and 4.9% seen in cases without a common channel. In pancreaticobiliary maljunction cases, incidence of associated gallbladder carcinoma was 72.7%. CONCLUSION: The presence of an obvious common channel was observed in 37.0%. A close relationship is suggested between the presence of a common channel and development of gallbladder carcinoma and acute pancreatitis.     

Long-term follow-up of intraductal papillary adenoma of the pancreas

Intraductal papillary mucinous tumors of the main pancreatic duct are often considered to be premalignant or malignant, and therefore surgical resection is recommended. We report two autopsy cases of intraductal papillary mucinous tumor of the pancreas following long-term observation. The first patient was an 84-year-old man with early gastric cancer treated by endoscopic mucosectomy. The second patient was a 77-year-old man with hepatocellular carcinoma treated by percutaneous pure ethanol injection and transarterial embolization. In both patients, endoscopic retrograde pancreatography showed a diffusely dilated main pancreatic duct, with intraductal filling defects expressing mucus, as well as dilated side branches. Obvious intramural nodules were not detected. Due to their advanced age and personal requests, both patients were managed conservatively and followed nonoperatively. In the first patient, serial pancreatograms showed progression of the pancreatic duct dilatation. Both patients died of gastric cancer, the first patient 7¹/₂ years and the second, 10 years after first presentation, respectively. Autopsies revealed extensive intraductal papillary adenoma throughout the dilated mucus-filled main pancreatic duct. However, there was no evidence of progression to adenocarcinoma. Based on these observations, we suggest that, in patients with intraductal papillary mucinous tumor of the pancreas without obvious intramural nodules, even if the tumor is in the main pancreatic duct, pancreatectomy may not be mandatory, particularly in the elderly. Received: March 21, 2001 / Accepted: July 6, 2001 Reprint requests to: T. Kamisawa     

Pathologic changes in the non-carcinomatous epithelium of the gallbladder in patients with a relatively long common channel

BACKGROUND: Except for pancreaticobiliary maljunction, the relationship between a relatively long common channel and gallbladder carcinoma is unknown. METHODS: For purposes of this study, a high confluence of pancreaticobiliary ducts was defined as a common channel that is 6 mm or greater in length, together with occlusion of the communication between the pancreatic and bile ducts during sphincter contraction. Pancreaticobiliary maljunction and high confluence of the pancreaticobiliary ducts were detected in 69 (2.1%) and 54 (1.6%), respectively, of 3300 consecutive patients who underwent ERCP. Proliferation activity and genetic alteration were examined in the non-carcinomatous epithelium of the gallbladder in patients with these two radiographic findings at ERCP. RESULTS: The Ki-67 labeling index in the epithelium in cases of a high confluence of the pancreaticobiliary ducts and pancreaticobiliary maljunction without biliary dilatation was significantly greater than that in cases of gallbladder carcinoma without these anomalies (p < 0.01). Overexpression of p53 and K-ras mutations were detected in, respectively, 22.2% and 27.8% of cases of a high confluence of pancreaticobiliary ducts. CONCLUSIONS: A relatively long common channel may be an important risk factor for the development of gallbladder carcinoma. Vigilance for the development of gallbladder carcinoma is indicated in patients with a relatively long common channel, in addition to those with pancreaticobiliary maljunction.