Resected case of eosinophilic cholangiopathy presenting with secondary sclerosing cholangitis

Eosinophilic cholangiopathy is a rare condition characterized by eosinophilic infiltration of the biliary tract and causes sclerosing cholangitis. We report a patient with secondary sclerosing cholangitis with eosinophilic cholecystitis. A 46-year-old Japanese man was admitted to our hospital with jaundice. Computed tomography revealed dilatation of both the intrahepatic and extrahepatic bile ducts, diffuse thickening of the wall of the extrahepatic bile duct, and thickening of the gallbladder wall. Under the diagnosis of lower bile duct carcinoma, he underwent pyloruspreserving pancreatoduodenectomy and liver biopsy. On histopathological examination, conspicuous fibrosis was seen in the lower bile duct wall. In the gallbladder wall, marked eosinophilic infiltration was seen. Liver biopsy revealed mild portal fibrosis. He was diagnosed as definite eosinophilic cholecystitis with sclerosing cholangitis with unknown etiology. The possible etiology of sderosing cholangitis was consequent fibrosis from previous eosinophilic infiltration in the bile duct. The clinicopathological findings of our case and a literature review indicated that eosinophilic cholangiopathy could cause a condition mimicking primary sclerosing cholangitis （PSC）. Bile duct wall thickening in patients with eosinophilic cholangitis might be due to fibrosis of the bile duct wall. Eosinophilic cholangiopathy might be confused as PSC with eosinophilia.     

Pathophysiology of acute obstructive cholangitis

Because acute obstructive cholangitis is life-threatening, understanding of the pathophysiology of this disease is required to establish a medical treatment. Experimental results indicate that obstruction of the bile duct itself does not induce acute cholangitis, but infection of gut-derived bacteria such asEscherichia coli into the bile triggers fatal septicemia, which leads to liver injury and renal failure. In obstructive cholangitis, functional changes in sinusoidal lining cells are often seen. Mediators produced by Kupffer cells, endothelial cells, and stellate cells may modulate inflammatory reactions especially in the periportal area of bile duct ligated animals. In addition, proliferation of bile duct epithelial cells is induced by bile duct ligation. Recently, nitric oxide has been recognized as an important mediator of multiple organ failure. Actually, when bile duct ligated animals are treated with endotoxin, metabolites of nitric oxide in blood and plasma increase, indicating that nitric oxide may take part in the pathophysiology of acute obstructive cholangitis.     

A localized primary sclerosing cholangitis preoperatively diagnosed as hilar cholangiocarcinoma; report of a case

The authors report herein a case of primary sclerosing cholangitis localized to the hepatic hilum which occurred in a 67-year-old male. The direct cholangiography revealed bile duct stenosis from the common hepatic duct to bilateral hepatic ducts. We could not confirm bile duct malignancy, however, hilar cholangiocarcinoma was most suspicious. We performed right trisegmentectomy of the liver with caudate lobectomy and lymph node dissection 3 weeks after right portal embolization. Pathological findings confirmed localized primary sclerosing cholangitis. Surgical resection of the affected bile duct is most effective in localized primary sclerosing cholangitis, because the prognosis of the disease is poor and secondary carcinogenesis in primary sclerosing cholangitis has high incidence.     

Risk factors for acute suppurative cholangitis caused by bile duct stones

OBJECTIVE: Acute suppurative cholangitis is fatal unless adequate biliary drainage is obtained in a timely manner. The major cause of acute suppurative cholangitis is bile duct stones, but it is not known which patients with bile duct stones are likely to develop acute suppurative cholangitis. METHODS: Between May 1994 and December 2005, 343 consecutive patients with bile duct stones were referred to our department. Of these, 38 patients presented with acute suppurative cholangitis. A nasobiliary catheter or biliary stent was emergently inserted endoscopically to control acute suppurative cholangitis in those patients. Risk factors for the development of acute suppurative cholangitis in the 343 patients were investigated using univariate and multivariate analyses. RESULTS: A nasobiliary catheter or stent was inserted endoscopically in all 38 patients with acute suppurative cholangitis. Although biliary drainage was considered to be effective in all patients, two patients (5.3%) died of deteriorating comorbid diseases despite subsiding cholangitis. In the univariate analysis, age >or=70 years, neurological disease, and peripapillary diverticulum were identified as risk factors for the development of acute suppurative cholangitis. In the multivariate analysis, these three factors remained significant. CONCLUSIONS: Advanced age, comorbid neurological disease, and peripapillary diverticulum were identified as independent risk factors for the development of acute suppurative cholangitis in patients with bile duct stones.     

Bile duct carcinoma in patients with ulcerative colitis

Six cases of bile duct carcinoma were encountered among 1207 patients with ulcerative colitis, a prevalence rate of 0.5%. The relative risk of bile duct carcinoma in patients with ulcerative colitis was 31.3. Colitis was extensive in all six patients with a mean duration of 23.2 years before the diagnosis of carcinoma. The mean age at the diagnosis of carcinoma was 38.5 years. Three patients had undergone colectomy 5–16 years earlier, and in four patients pericholangitis and sclerosing cholangitis preexisted. The tumors, histologically adenocarcinomas, were located in the common bile duct in five patients and in the hepatic duct in one. The mean survival was 11.8 months (one patients is still alive with recurrent carcinoma). Pericholangitis and sclerosing cholangitis is a frequent preexisting lesion in patients with bile duct carcinoma complicating ulcerative colitis and may be considered a premalignant lesion in these patients. Both sclerosing cholangitis and bile duct carcinoma are rare in Crohn's disease.     

A case of follicular cholangitis mimicking hilar cholangiocarcinoma

Follicular cholangitis is a sclerosing cholangitis with hilar biliary stricture that must be differentiated from both immunoglobulin G4-related sclerosing cholangitis and primary sclerosing cholangitis. This disorder is extremely rare and difficult to distinguish from hilar biliary cholangiocarcinoma. We report here a case of a Japanese female patient in her 60s with this disease. The patient visited a family doctor for itching and general fatigue. Blood examination showed elevated hepatobiliary enzyme levels. Various imaging studies showed dilation of the bilateral intrahepatic bile duct and wide stenosis from the proximal bile duct to the right and left hepatic duct. They also showed the enlargement of multiple lymph nodes in the hepatoduodenal ligament, periaorta, and mesocolon. Based on endoscopic retrograde cholangiopancreatography-directed brush cytology, we diagnosed this patient with hilar cholangiocarcinoma and performed left trisegmentectomy of the liver. The pathology results showed that the wall from the bilateral hepatic duct to the proximal bile duct had thickened irregularly with dense fibrosis and a marked formation of lymph follicles. The mucosal epithelia did not have malignant findings. The diagnosis was follicular cholangitis. This case indicates that follicular cholangitis should be considered as a differential diagnosis of hilar biliary stricture.     

Diagnosis of sclerosing cholangitis with technetium 99m-labeled iminodiacetic acid planar and single photon emission computed tomographic scintigraphy

The purpose of this study was to determine whether 99mTc-iminodiacetic acid planar biliary scintigraphy combined with single photon emission computed tomography could detect sclerosing cholangitis and provide additional information regarding the extent and severity of disease. Thirteen patients with sclerosing cholangitis and 13 normal control subjects were studied. Scintigraphic results were also compared with previously reported studies of patients with isolated common bile duct obstruction and with primary biliary cirrhosis. The planar scintigraphy in patients with sclerosing cholangitis showed beading or bandlike constrictions of the biliary tract corresponding to lesions seen on cholangiography, and the image pattern was distinctly different from images obtained from patients with isolated common bile duct obstruction or primary biliary cirrhosis. The single photon emission computed tomography images of the liver in patients with sclerosing cholangitis demonstrated multiple focal areas of 99mTc-iminodiacetic acid retention, representing bile stasis in intrahepatic bile ducts. Compared to controls, the mean hepatic clearance half-time of 99mTc-iminodiacetic acid was markedly delayed in patients with sclerosing cholangitis (6-10 times normal). Individual patients with sclerosing cholangitis had wider variation in isotope clearance half-time from three regions of the liver than patients with isolated common bile duct obstruction, consistent with regional difference in disease severity and variable impairment of bile flow. In 4 patients with sclerosing cholangitis with incomplete filling of the right and left hepatic ducts at cholangiography, planar and single photon emission computed tomographic scintigraphy provided evidence of significant intrahepatic sclerosing cholangitis. In conclusion, combined 99mTc-iminodiacetic acid planar and single photon emission computed tomographic scintigraphy is a sensitive noninvasive test for the diagnosis of sclerosing cholangitis and reliably differentiates sclerosing cholangitis from isolated common bile duct obstruction or primary biliary cirrhosis. Measurement of isotope clearance half-time provides quantitative physiologic data that may be useful in the longitudinal follow-up of patients with sclerosing cholangitis.     

Xanthogranulomatous cholangitis causing obstructive jaundice： A case report

This article reports the case of a 34-year-old woman with xanthogranulomatous cholangitis who developed obstructive jaundice. Microscopically, the bile duct was surrounded and narrowed by a xanthogranulomatous lesion, but no xanthogranulomatous cholecystitis was seen. Although percutaneous cholangiograms done via the transhepatic biliary drainage showed smooth narrowing of the upper to middle bile duct, the cytology of bile was diagnosed as class V adenocarcinoma. Therefore, right extended hepatectomy and extrahepatic bile duct resection were performed. The differentiation of benign and malignant strictures at the hepatic hilum is often difficult. Xanthogranulomatous cholangitis is one possible diagnosis of a bile duct stricture. Precise review of all the preoperative information is required to make a correct diagnosis.     

Bile duct antibodies crossreacting with blood group antigens in primary sclerosing cholangitis.

Indirect immunoperoxidase histochemistry was used to localise and determine the disease, species, and tissue specificity of bile duct antibodies in primary sclerosing cholangitis. Serum was collected from: 29 patients with primary sclerosing cholangitis, 18 patients with ulcerative colitis alone, 19 patients with extrahepatic biliary obstruction of other causes, and 42 healthy control subjects. Bile duct antibodies reacted with an antigen localised to the small and large intrahepatic bile ducts. When blood group A human liver was used they were detected in 34% of patients with primary sclerosing cholangitis. They were not detected when blood group O human liver was used. Bile duct antibodies that reacted with obstructed and normal rabbit liver were detected in 34% and 17% respectively of patients with primary sclerosing cholangitis but were also present in similar proportions of control subjects. Colon antibodies that reacted with human and rabbit colon were found in 52% and 24% respectively of patients with primary sclerosing cholangitis. Absorption studies using blood group substances A and B abolished the reactivity of bile duct antibodies with human and rabbit liver and that of colon antibodies' with rabbit colon. Colon antibodies that reacted with human colon were not absorbed. Absorption studies using isolated peripheral white blood cells did not affect reactivity of bile duct or colon antibodies. We conclude that bile duct antibodies are disease, species, and tissue non-specific and react with blood group A/B antigens present in human and rabbit bile ducts and rabbit colon. This suggests that they do not play a role in the pathogenesis of primary sclerosing cholangitis.     

Endoscopic removal of large common bile duct stones in recurrent pyogenic cholangitis

It is not uncommon to find large stones obstructing the bile duct in patients with recurrent pyogenic cholangitis. In a series of 291 patients with cholangitis, 32 patients had stones more than 2 cm in diameter. Endoscopic extraction using a combination of large baskets, 1% EDTA flushing, and manual or mechanical lithotripsy allowed the common bile duct to be cleared in 50% of patients. Lack of space in the common bile duct to open the retrieval basket because of stone impaction was the major reason for failure.     

Angioleiomyoma of the Common Bile Duct

ABSTRACT An 80-year-old woman with angioleiomyoma in the common bile duct is described. Apart from weakness and jaundice, the patient had no signs or symptoms until after endoscopic retrograde cholangiopancreatography, when cholangitis and septicaemia due to Pseudomonas aeruginosa developed. X-ray during endoscopy revealed a tumour obstructing the common bile duct and was assumed to be malignant. Because the patient was so old and her general condition had deteriorated, no treatment was given. Autopsy revealed a benign angioleiomyoma of the common bile duct and suppurative cholangitis, the latter obviously caused by the endoscopy.     

Hypereosinophilia, Ulcerative Colitis, Sclerosing Cholangitis, and Bile Duct Carcinoma

A case of ulcerative colitis and pericholangitis-sclerosing cholangitis bile duct carcinoma complex associated with hypereosinophilia and possibly the hypereosinophilic syndrome is reported, and the association of eosinophilia with various hepatobiliary and gastrointestinal diseases is discussed. Hypereosinophilia may foretell a more serious underlying condition such as bile duct carcinoma in some patients with primary sclerosing cholangitis.     

Follicular cholangitis mimicking cholangiocarcinoma treated with right hepatectomy: A case report and review of published works

Follicular cholangitis is a new, rare disease that causes severe biliary stricture. We herein describe the findings from a resected case of follicular cholangitis, suggesting a distinct disease entity that causes benign biliary stricture. A 60‐year‐old man who was referred to our hospital due to elevated γ‐glutamyl transpeptidase levels and dilatation of the B8 bile duct. Although bile juice cytology and bile duct brushing cytology showed no malignancy, the dilatation was progressive. Therefore, right hepatectomy combined with caudate lobectomy was carried out on suspicion of intrahepatic cholangiocarcinoma. The wall of the resected bile duct was markedly thickened due to severe fibrosis under the mucosal layer. Histology of the mucosal epithelium indicated no malignancy. Infiltration of plasma cells characterized by remarkable formation of lymphoid follicles with germinal centers was observed around the bile ducts. The patient was diagnosed with follicular cholangitis based on histological findings. We thus observed a rare case of follicular cholangitis. This case and review of published reports suggest that, despite its rarity, follicular cholangitis should be considered at the differential diagnosis of biliary stricture. This case report could contribute to a better understanding of how to address this disease.     

Pathology and pathogenesis of intrahepatic bile duct loss

In recent years, the pathology and pathogenesis of bile duct loss have been extensively studied, and a num‐ber of hepatobiliary diseases have been added to the list of ductopenic diseases. In addition, the biology of biliary epithelial cells is now being studied with respect to bile duct loss, as well as biliary epithelial neoplasia. In this review, recent advances in pathogenetic and pathological studies of intrahepatic bile duct loss are described, with an emphasis on immune‐mediated cholangiopathies. The bile duct loss, an acquired and pathologic process that occurs in the biliary tree, is recognizable as an absence of bile duct in an individual portad tract, and also as such absence in the vicinity of parallel running hepatic arterial branches that constitute the portal triad. Immunostaining with biliary cytokeratin and other carbohydrate materials is useful for the identification of biliary elements in the inflamed portal tracts or fibrous septa. The underlying processes responsible for bile duct loss include immunological, ischemic, infectious, metabolic, and toxic processes. Bile duct loss in primary biliary cirrhosis and primary sclerosing cholangitis is immune‐mediated, that in interventional radiology using hepatic arterial branches is related to biliary ischemia, while that in hepatic allograft rejection is related to both immunological and ischemic insults. Bacterial and viral cholangitis with bile duct loss is an example of infectious cholangitis. The biliary tree maintains its homeostasis by renewal and dropout, and bile duct loss occurs mainly via biliary apoptosis. In some patients with bile duct loss, such as occurs in drug‐induced injuries, the bile ducts regenerate and finally redistribute in the liver, while in other types of bile duct loss, the loss is progressive and is followed by vanishing bile duct syndrome, leading to biliary cirrhosis or liver transplantation. More analysis of the biology of biliary epithelial cells is mandatory for the evaluation of the pathobiology of bile duct loss, as well as for the effective restoration of biliary epithelial cells, in ductopenic liver diseases.     

Assessment of serum and bile levels of CA19-9 and CA125 in cholangitis and bile duct carcinoma

In this study, CA19-9 and CA125 in serum and bile were measured to evaluate their diagnostic value in cholangitis and bile duct carcinoma. Patients were classified into three groups: group A, the control group, had cholelithiasis without infection (n = 23), group B had acute cholangitis (n = 25) and group C had bile duct carcinoma without bacterial infection (n = 18). All patients had undergone surgery, and bile and serum of the patients were measured for the two tumour markers by radio-immunoassay. The positivity rate for serum CA19-9 was 4.4% in the control group, 28.0% in group B and 61.1% in group C. The positivity rates for serum CA125 in groups control, B and C were 0%, 4% and 27.78% respectively. The diagnostic accuracy for bile duct carcinoma was 67.4% for both CA19-9 or CA125. The concentration of CA19-9 in bile was more than 1200 ng/mL in 72% of patients with acute cholangitis, in 61.1% of all patients with bile duct carcinoma and 0% in the control group. The frequency of concentrations of CA125 in bile greater than 200 ng/mL was 38.89% in bile duct carcinoma and none was observed in the control or acute cholangitis groups. In conclusion, the concentration of CA19-9 was increased not only by the tumour itself, but also by infection. In the diagnosis of bile duct carcinomas, the sensitivity of CA125 was low but its specificity was very high.     

Cytomegalovirus cholangitis and pancreatitis in an immunocompetent patient

Cholangitis and pancreatitis associated with cytomegalovirus (CMV) infection in an immunocompetent patient is reported. Endoscopic retrograde cholangiography performed on a 55-year-old man for evaluation of the cause of jaundice and liver dysfunction revealed a distal focal irregular narrowing of the common bile duct. Microscopic findings of the resected specimen showed chronic cholangitis and CMV pancreatitis. Immunohistochemistry disclosed that epithelial cells in the inflamed bile duct were positive for CMV antigen, which was compatible with CMV cholangitis. Inflammation of the biliary tract or pancreas by CMV has been commonly reported as a complication in immunocompromised patients. Our report appears to be a rare case, but suggests that CMV cholangitis or pancreatitis should be considered in the differential diagnoses of common bile duct stenosis or pancreatitis even in immunocompetent individuals.     

Are bile duct lesions of primary biliary cirrhosis distinguishable from those of autoimmune hepatitis and chronic viral hepatitis? Interobserver histological agreement on trimmed bile ducts

Background Primary biliary cirrhosis (PBC) is histopathologically characterized by chronic nonsuppurative destructive cholangitis and ductopenia of interlobular bile ducts. Bile duct injury is also often encountered in chronic viral hepatitis (CVH) and in autoimmune hepatitis (AIH).Methods In this study, we performed interobserver agreement analysis on 90 injured bile ducts from liver specimens of PBC (17 cases), CVH (26 cases), and AIH (18 cases), with 30 bile ducts chosen from each disease group. Digital images of bile ducts with minimal periductal elements were recorded in CD-ROM format and sent to 14 observers (six special hepatopathologists, four local hepatopathologists, and four general pathologists). We analyzed the following issues: (1) diagnostic accuracy of PBC, based only on bile duct lesions; (2) classification of bile duct lesions in AIH cases as destructive cholangitis equivalent to PBC-associated injury, or not.Results The diagnostic accuracy of PBC cases with severe bile duct injuries was very high (over 80%), although the accuracy in cases with only mild bile duct injuries was low (50% or less). For AIH, each observer classified 9 of the 30 bile ducts, on average, as destructive cholangitis.Conclusions This study revealed that 66.9% of PBC cases could be diagnosed based on trimmed bile ducts alone. Bile duct injury similar to that in PBC could be encountered in AIH.     

Histological analysis of liver parenchyma and choledochal wall, and external diameter and intraluminal pressure of the common bile duct in controls and patients with common bile duct stones with and without acute suppurative cholangitis

The purpose of this prospective controlled study was to determine the changes in intraluminal pressure and diameter of the common bile duct in a total of 121 bile patients with choledocholithiasis, and the consequences of these alterations for choledochal mucosa and liver histology. In fact, the reflux of bacteria from the obstructed biliary tract into the bloodstream is responsible for producing the clinical syndrome of acute suppurative cholangitis. Group I (26 patients) served as controls, Group II (50) had choledocholithiasis with clear green bile, and Group III (45) were patients with acute suppurative cholangitis with pus in the biliary tract. Ultrasonography revealed gallstones in all the patients. The external diameter of the common bile duct in patients with choledocholithiasis and acute suppurative cholangitis was significantly greater than in those of the other groups. Patients with acute suppurative cholangitis also had a higher intraluminal pressure than those of Groups I or II.     

Biliary lavage with corticosteroids in primary sclerosing cholangitis. A clinical, cholangiographic and bacteriological study

Bile duct perfusion with corticosteroids is reported to improve the cholangiographic and biochemical abnormalities in some patients with primary sclerosing cholangitis. In a randomised placebo controlled trial, thirteen consecutive patients received continuous bile duct irrigation with either normal saline (1 l/day) or normal saline plus hydrocortisone (100 mg daily) via a nasobiliary tube placed in a hepatic duct at endoscopic retrograde cholangio-pancreatography. Eleven patients completed lavage for 2 weeks but no cholangiographic changes were observed in either group. Liver function tests deteriorated during lavage, but later returned to pre-treatment levels. Although bile was sterile at start of lavage, a wide range of bacteria was isolated from bile in all patients during treatment, and cholangitis with septicaemia occurred in 2 patients. We conclude that nasobiliary lavage is not beneficial in treating primary sclerosing cholangitis.     

Intrahepatic cholangiectases and large-duct obliteration in primary sclerosing cholangitis

We studied intrahepatic bile ducts of five patients with chronic ulcerative colitis and primary sclerosing cholangitis. The livers had been obtained at the time of orthotopic liver transplantation. After specimen cholangiography and perfusion fixation, sequential blocks and sections from portal tracts were studied, combining light microscopy with scanning electron microscopy. In vivo cholangiograms were studied also. The specimens revealed: absence of normal bile ducts; presence of thin-walled tubular or saccular cholangiectases with semicircular and annular fibrous crests, without evidence of superinfection; cholangiectases with secondary acute or chronic-cellular cholangitis, with or without cholangitic abscesses; fibrous cholangitis without ductal dilatation; transformation of bile ducts into fibrous cords which were either solid or contained remnants of bile duct epithelium, and complete loss of bile ducts. The shape and distribution of the cholangiectases suggested that these lesions were manifestations of the disease process and not passively dilated normal ducts. Fibrous-obliterative cholangitis with formation of fibrous cords was found not only at the level of interlobular and adjacent septal bile ducts but also at the level of segmental bile ducts that normally would have been demonstrable in cholangiograms. The "pruned-tree" appearance in cholangiograms appears to result from the transition between patent and often cholangiectatic ducts, and duct obliteration. At present, intrahepatic cholangiectases in association with duct obliteration can be considered pathognomonic morphologic features of primary sclerosing cholangitis.