Clinicopathological differentiation between sclerosing cholangitis with autoimmune pancreatitis and primary sclerosing cholangitis

Background The present study was undertaken to identify the clinicopathological differences between sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and primary sclerosing cholangitis (PSC). Methods We retrospectively compared the clinical, cholangiographic, and liver biopsy findings between 24 cases of PSC and 24 cases of SC-AIP. Results Patient age at the time of diagnosis was significantly lower in the PSC group than in the SC-AIP group. The peripheral blood eosinophil count was significantly higher in the PSC group than in the SC-AIP group, but the serum IgG4 level was significantly higher in the SC-AIP group. Cholangiography revealed band-like strictures, beaded appearance, and pruned-tree appearance significantly more frequently in PSC, whereas segmental strictures and strictures of the distal third of the common bile duct were significantly more common in SC-AIP. Liver biopsy revealed fibrous obliterative cholangitis only in the PSC specimens. No advanced fibrous change corresponding to Ludwig's stages 3 and 4 was observed in any of the SC-AIP specimens. IgG4-positive plasma cell infiltration of the liver was significantly more severe in SC-AIP than in PSC. Subsequent cholangiography showed no improvement in any of the PSC cases, but all SC-AIP patients responded to steroid therapy, and improvement in the strictures was observed cholangiographically. Conclusions Based on the differences between the patients' ages and blood chemistry, cholangiographic, and liver biopsy findings, SC-AIP should be differentiated from PSC.     

A case of primary sclerosing cholangitis mimicking chronic pancreatitis

Summary A case of a 37 year old male is presented, who died from primary sclerosing cholangitis (PSC) with characteristic radiological picture and laboratory data suggesting chronic pancreatitis (CP).     

Sclerosing cholangitis associated with autoimmune pancreatitis

Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by irregular narrowing of the pancreatic duct, pancreatic swelling, and a favorable response to corticosteroids, in which the autoimmune mechanism is postulated in the pathogenesis. High serum immunoglobulin (Ig)G4 concentrations and various types of extrapancreatic involvement are prominent features of this disease. Sclerosing cholangitis is a major extrapancreatic lesion of autoimmune pancreatitis that has been regarded as primary sclerosing cholangitis (PSC) complicating chronic pancreatitis. Because sclerosing cholangitis associated with autoimmune pancreatitis (SC-AIP) also favorably responds to corticosteroid therapy, it should be differentiated from PSC. Useful points regarding the differentiation between SC-AIP and PSC are as follows: (i) PSC occurs in younger and SC-AIP in older individuals; (ii) obstructive jaundice is more frequently seen in SC-AIP; (iii) PSC is complicated with inflammatory bowel disease, whereas SC-AIP is complicated with so called extrapancreatic lesions of AIP; (iv) high serum IgG4 concentrations are frequently seen in SC-AIP; (v) a cholangiogram may differentiate the two conditions to some extent; (vi) abundant IgG4-bearing plasma cell infiltration is seen in SC-AIP; and (vii) steroid therapy is effective for SC-AIP. IgG4-related sclerosing cholangitis without pancreatic lesion may be a metachronous phenotype of SC-AIP, and also should be differentiated from PSC. The pathogenesis of AIP and SC-AIP remains unclear. The complement activation system of the classical pathway may be contributing in some cases.     

Sclerosing pancreatitis presenting as a periampullary tumour

BackgroundSclerosing lesions of the pancreatic duct are rare and may be secondary to primary sclerosing cholangitis (PSC) or the result of a primary sclerosing process (the recently described lymphoplasmacystic sclerosing pancreatitis, LSP). Occasionally this process may present as a mass lesion.Case outlineA 21 -year-old man presented with abdominal pain and jaundice, giving a high index of suspicion for a periampullary malignancy. There were minimal symptoms suggestive of PSC. The resected head of the pancreas demonstrated changes of chronic pancreatitis with a fibro-inflammatory process of the pancreatic duct suggesting an underlying ductal sclerosing process.DiscussionClinical presentation and imaging characteristics of PSC involving the pancreas are often misleading and may suggest a neoplasm as the underlying disorder. Conclusive diagnosis is usually not determined until after surgical intervention. Although racial differences in pancreatic duct involvement have been suggested, the underlying histopathology is the same as in PSC involving the biliary ducts.     

Sclerosing cholangitis associated with autoimmune pancreatitis differs from primary sclerosing cholangitis

AIM： To clarify the characteristic features of biliary lesions in patients with autoimmune pancreatitis （AIP） and compare them with those of primary sclerosing cholangitis （PSC）.METHODS： The clinicopathological characteristics of 34 patients with sclerosing cholangitis （SC） associated with AIP were compared with those of 4 patients with PSC.RESULTS： SC with AIP occurred predominantly in elderly men. Obstructive jaundice was the most frequent initial symptom in SC with AIP. Only SC patients with AIP had elevated serum IgG4 levels, and sclerosing diseases were more frequent in these patients. SC patients with AIP responded well to steroid therapy. Segmental stenosis of the lower bile duct was observed only in SC patients with AIP, but a beaded and prunedtree appearance was detected only in PSC patients.Dense infiltration of IgG4-positive plasma cells was detected in the bile duct wall and the periportal area, as well as in the pancreas, of SC patients with AIP.CONCLUSION： SC with AIP is distinctly different from PSC. The two diseases can be discriminated based on cholangiopancreatographic findings and serum IgG4 levels.     

Lymphoplasmacytic sclerosing pancreatocholangitis successfully treated by pancreatoduodenectomy

A 68‐year‐old man complaining of jaundice was admitted to our hospital in October 1996. Radiological imaging studies, including dynamic computed tomography, endoscopic retrograde cholangiography, and angiography, were highly suggestive of pancreatic head cancer, and laparotomy was performed on October 25, 1996. On gross examination, the pancreas appeared firm, as in chronic pancreatitis, with a mass lesion in the pancreatic head measuring 35 × 35 × 25 mm. A pylorus‐preserving pancreatoduodenectomy was carried out. Histological findings were characterized by uniform fibrosis with diffuse lymphoplasmacytic infiltration and lymph follicles in the thickened wall of the bile duct and in and around the pancreas, with acinar atrophy. The histological diagnosis was lymphoplasmacytic sclerosing pancreatocholangitis. Approximately 5 years postoperatively, the patient was alive and well without adjunctive corticosteroid therapy. This positive result suggests that pancreatoduodenectomy may be effective for lymphoplasmacytic sclerosing pancreatocholangitis that is localized in the pancreatic head.     

Isolated intrapancreatic Ig G4-related sclerosing cholangitis

Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is frequently associated with type 1 autoimmune pancreatitis(AIP). Association with AIP can be utilized in the diagnosis of Ig G4-SC. However, some cases of Ig G4-SC are isolated from AIP, which complicates the diagnosis. Most of the reported cases of isolated Ig G4-SC displayed hilar biliary strictures, whereas isolated Ig G4-SC with intrapancreatic biliary stricture is very rare. Recently, we have encountered 5 isolated intrapancreatic Ig G4-SC cases that were not associated with AIP, three of which were pathologically investigated after surgical operation. They all were males with a mean age of 74.2 years. The pancreas was not enlarged in any of these cases. No irregular narrowing of the main pancreatic duct was found. Bile duct wall thickening in lesions without luminal stenosis was detected by abdominal computed tomography in all five cases, by endoscopic ultrasonography in two out of four cases and by intraductal ultrasonography in all three cases. In three cases, serum Ig G4 levels were within the normal limits. The mean serum Ig G4 level measured before surgery was 202.1 mg/d L(4 cases). Isolated intrapancreatic Ig G4-SC is difficult to diagnose, especially if the Ig G4 level remains normal. Thus, this type of Ig G4-SC should be suspected in addition to cholangiocarcinoma and pancreatic cancer if stenosis of intrapancreatic bile duct is present.     

Pancreatic duct changes are not associated with early signs of chronic pancreatitis at magnetic resonance imaging (MRI) in patients with primary sclerosing cholangitis

Abstract

Objective. The association between chronic pancreatitis (CP) and primary sclerosing cholangitis (PSC) has been reported previously. The aims of the present study were to evaluate the presence of early pancreatic abnormalities and duct changes, using MRCP/MRI in PSC and to evaluate possible risk factors for these changes and their clinical importance. Materials and methods. One hundred and three patients with PSC were identified among all MRI liver/pancreas referrals in 2001–2005. MRCP was used to grade pancreatic duct changes in three groups: grade 0 (normal), grade 1 (mild) and grade 2 (severe). For detection of early MRI signs of CP, the pancreas-spleen signal intensity ratio (SIR), the arterial and early venous phase ratio (A/PV ratio) and the age-related size of the pancreas were evaluated. Results. Pancreatic duct changes were found in 24% of the PSC patients. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but not associated with pancreas-spleen SIR, A/PV ratio, pancreas size, previous post-ERCP or acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Clinically significant CP was seen in one PSC patient (1%). Conclusions. Pancreatic duct changes are associated with extrahepatic bile duct strictures and not with the early MRI signs of CP. Therefore, pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as CP. Pancreatic duct changes are of limited clinical importance but may contribute to abdominal pain in PSC.     

环磷酰胺治疗原发性硬化性胆管炎的疗效观察

目的 探讨环磷酰胺治疗原发性硬化性胆管炎（PSC）的临床疗效.方法 选择2004年1月-2012年12月在本院消化内科治疗的24例PSC患者作为观察对象,随机分为观察组13例和对照组11例,对照组常规应用熊去氧胆酸进行治疗,观察组应用熊去氧胆酸和环磷酰胺进行治疗,两组患者治疗4周后,比较两组患者的临床疗效、胆红素的变化及用药后的不良反应.计数资料采用Fisher确切概率法,计量资料采用独立样本的t检验和配对样本的t检验进行分析.结果 对照组的有效率为45.45%,观察组的有效率为84.62%,观察组明显高于对照组（P=0.0489）;观察组与对照组相比,治疗后TBil以及DBil改善明显,两组比较差异有统计学意义（t=12.45,P＜0.001;t=5.60,P＜0.001）.对照组治疗后的不良反应发生率为18.18%,观察组的不良反应发生率为23.08%,观察组的不良反应的发生率略高于对照组,差异无统计学意义（P=0.741）.结论 环磷酰胺治疗PSC临床疗效明显,不良反应的发生率在患者耐受范围内,故可在临床治疗中试用.     

Recent status of primary sclerosing cholangitis in Japan

Patients with primary sclerosing cholangitis (PSC) in Japan have two peaks in age distribution, one in their twenties and the other in their fifties and sixties. PSC patients in Japan have different characteristics from those in other countries: there is a higher incidence of eosinophilia (27%) and positivity for anti-nuclear antibody (30%), less frequent complication with inflammatory bowel diseases (IBD; 21%), and more frequent complication with chronic pancreatitis (15%). In younger patients in Japan (those aged less than 40 years), the incidence of positivity for anti-nuclear antibody was lower (20% vs 38% P < 0.05), complication with IBD was more frequent (39% vs 9% P < 0.01), complication with chronic pancreatitis was less frequent (4% vs 22% P < 0.01), and damage to both the intra- and extrahepatic bile ducts was more frequent (89% vs 56% P < 0.01) than in older patients (those aged 40 years or more). These findings suggest that younger PSC patients in Japan have characteristics similar to those of patients in other countries, and that in Japan older PSC patients have a different pathogenesis from that of younger patients.     

IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater's ampulla and the bile duct

Background and Aim: Autoimmune pancreatitis is commonly associated with immunoglobulin (Ig) G4‐related sclerosing cholangitis (IgG4‐SC). The discrimination between IgG4‐SC and pancreatobiliary malignancies or primary sclerosing cholangitis (PSC) is now an important issue. The present study was carried out to examine the usefulness of endoscopic biopsies from Vater's ampulla and the bile duct to diagnose IgG4‐SC. Methods: The present study included 29 IgG4‐SC patients (26 with both pancreatitis and cholangitis, and 3 with cholangitis only), 6 PSC patients, and 27 pancreatobiliary carcinoma patients. All patients underwent endoscopic biopsies from Vater's ampulla and the common bile duct. Biopsied specimens were histologically examined using immunostaining for IgG4. Results: For the ampullary and bile duct biopsies, the IgG4‐SC samples had a significantly greater number of IgG4‐positive plasma cells than the PSC or pancreatobiliary carcinoma specimens. In addition, bile duct biopsies from five patients (17%) with IgG4‐SC showed diffuse inflammatory cell infiltration with irregular fibrosis corresponding to the histological features of lymphoplasmacytic sclerosing pancreatocholangitis. Based on the threshold of 10 IgG4‐positive plasma cells per high power field, the diagnostic rates of the ampullar and bile duct biopsies were both 52% (15/29 cases). Twenty‐one patients (72%) had more than 10 IgG4‐positive plasma cells in at least one biopsy. The bile duct biopsy was significantly valuable for IgG4‐SC patients with swelling of the pancreatic head. Conclusion: The present study suggested that ampullar and bile duct biopsies are useful for diagnosing IgG4‐SC.     

Primary sclerosing cholangitis in Japan—analysis of 192 cases

Primary sclerosing cholangitis is very rare in Japan. The aim of the present study was to identify the characteristics of such patients in Japan. A questionnaire was sent to the members of the Japanese Society of Gastroenterology and responses for 192 cases were analyzed. There was male predominancy (61%), and two peaks in the age distribution at diagnosis (20–30 years and 50–70 years). Bile duct damage was mainly intra + extrahepatic (69%) versus intrahepatic (17%) or extrahepatic (14%). The incidences of eosinophilia and positivity for anti-nuclear antibody were 27% and 30%, respectively. The incidence of associated inflammatory bowel disease was 21 % (38 ulcerative colitis and 2 Crohn's disease). Chronic pancreatitis, gallstones, and biliary cancers occurred in 15%, 12%, and 4%, respectively, of the 192 patients. Patients less than 40 years of age had a higher incidence than the patients 40 years old or more of damage intra + extrahepatic bile ducts (89% vs 56%) and of associated ulcerative colitis (36% vs 9%), whereas the incidence of chronic pancreatitis was lower in patients aged less than 40 years (4%). The characteristics of patients with primary sclerosing cholangitis in Japan differ from those in other countries in regard to age distribution and the incidence of complications, and at least two different groups of patients seem to exist in terms of the degree of bile duct damage and the incidence of complications.     

Autoimmune pancreatitis and multiple bile duct strictures treated effectively with steroid

Received: October 9, 2001 / Accepted: May 17, 2002 RID="*" ID="*" Reprint requests to: K. Kimura     

Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease

Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum γ-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, “IgG4-related sclerosing disease”, and suggest that AIP is a pancreatic lesion reflecting this systemic disease.     

Two cases with hepatic amyloidosis suspected of having primary sclerosing cholangitis

Sclerogenic biliary changes in hepatic amyloidosis are seldom observed. Here, we report two recent cases initially suspected as primary sclerosing cholangitis (PSC), which were later diagnosed as hepatic amyloidosis (AL type). Case 1: On the basis of magnetic resonance cholangiopancreatography (MRCP) findings, PSC was suspected in a 41‐year‐old woman with jaundice. Computed tomography (CT) showed nodular pulmonary lesions and swollen cervical, mediastinal and para‐aortic lymph nodes, the cause of which was unknown despite detailed examinations. Because of rapid deterioration in the patient's liver function, living donor liver transplantation was performed. She was then diagnosed with hepatic amyloidosis, but died of heart failure due to cardiac amyloidosis 74 days after surgery. Case 2: On the basis of MRCP findings, PSC was suspected in a 49‐year‐old woman with jaundice. CT showed multiple cystic pulmonary lesions, and hypogammaglobulinemia was also observed (immunoglobulin G, 481 mg/dL). After a biliary plastic stent was placed, liver and lung biopsy confirmed the presence of amyloid deposition. These two cases indicate that it is important to consider hepatic amyloidosis as a differential diagnosis of PSC. The presence of atypical extrahepatic lesions may be useful clues for confirming the diagnosis.     

Death receptor 5 mediated-apoptosis contributes to cholestatic liver disease

Chronic cholestasis often results in premature death from liver failure with fibrosis; however, the molecular mechanisms contributing to biliary cirrhosis are not demonstrated. In this article, we show that the death signal mediated by TNF-related apoptosis-inducing ligand (TRAIL) receptor 2/death receptor 5 (DR5) may be a key regulator of cholestatic liver injury. Agonistic anti-DR5 monoclonal antibody treatment triggered cholangiocyte apoptosis, and subsequently induced cholangitis and cholestatic liver injury in a mouse strain-specific manner. TRAIL- or DR5-deficient mice were relatively resistant to common bile duct ligation-induced cholestasis, and common bile duct ligation augmented DR5 expression on cholangiocytes, sensitizing mice to DR5-mediated cholangitis. Notably, anti-DR5 monoclonal antibody-induced cholangitis exhibited the typical histological appearance, reminiscent of human primary sclerosing cholangitis. Human cholangiocytes constitutively expressed DR5, and TRAIL expression and apoptosis were significantly elevated in cholangiocytes of human primary sclerosing cholangitis and primary biliary cirrhosis patients. Thus, TRAIL/DR5-mediated apoptosis may substantially contribute to chronic cholestatic disease, particularly primary sclerosing cholangitis.