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PubMed1997

Endoscopic management of acute calculous cholangitis.

Acute cholangitis is associated with significant morbidity and mortality. Endoscopic drainage procedures have been shown to be a safe and effective mode of treatment in acute cholangitis. As there is paucity of large series on endoscopic management of acute cholangitis, a study was performed to evaluate safety and efficiency of endoscopic biliary decompression in acute cholangitis. The study included 89 consecutive patients (mean age 55+/-15 years; range 35-70 years; 50 males) with acute cholangitis requiring biliary drainage. Main presenting features were upper abdominal pain (84%), fever with chills (90%) and jaundice (74%). Altered sensorium, hypotension, features of peritonitis and acute renal failure were present in 15, 11, 18 and 5%, respectively. Endoscopic procedures performed were endoscopic sphincterotomy (ES) with stone extraction (n=40); ES with endoscopic nasobiliary drainage (ENBD; n=30); ENBD without ES (n=8); and ES with stent placement (n=11). Of the 89 patients, 85 (95%) responded within 48-72 h. Endoscopic common duct clearance could be achieved in 58 of 78 (74%) patients, whereas in 11 patients undergoing stent placement, stone extraction was not attempted. Complications included post-sphincterotomy bleed (n=2), retroduodenal perforation (n=1) and acute pancreatitis (n=1) with an overall complication rate of 4.4%. All the complications were seen in patients undergoing ES with stone extraction. Mortality was 3.3%. In conclusion, endoscopic biliary drainage is a safe and effective mode of treatment for acute cholangitis. Endoscopic nasobiliary drainage or stent placement is safer than ES in acute cholangitis as an initial step.

Acute Disease↗
PubMed1991

Histological and immunohistochemical study of the gall bladder lesion in primary sclerosing cholangitis.

The histological features and type of mononuclear cell infiltrate in gall bladders from six patients with primary sclerosing cholangitis were studied using routine staining techniques and immunohistochemistry. Control studies were performed using the gall bladders from six patients (age and sex matched) with chronic cholecystitis and four with primary biliary cirrhosis. A range of histological abnormalities was present in gall bladders from patients with primary sclerosing cholangitis including a mild to moderate degree of epithelial hyperplasia, pseudogland formation, and mononuclear cell infiltrate of the epithelium; moderate to severe chronic inflammatory cell infiltrate and fibrosis affecting the superficial and deep layers of the gall bladder wall; and minimal smooth muscle hypertrophy. These abnormalities were non-specific and were also present in gall bladders from patients with chronic cholecystitis and primary biliary cirrhosis. Vasculitis and granulomas were not present in the patients with primary sclerosing cholangitis. Immunohistochemistry showed that the superficial and deep mononuclear cell infiltrate in primary sclerosing cholangitis gall bladders was composed predominantly of lymphocytes, in contrast to chronic cholecystitis where macrophages were found in similar or greater numbers. Moreover, T lymphocytes (activated and resting) were present throughout the lymphocytic infiltrate and were apposed to the base and interdigitated between the biliary epithelial cells in significantly greater numbers than in chronic cholecystitis gall bladders. B lymphocytes were present only in lymphoid follicles. Comparative studies using liver biopsy specimens from three of the primary sclerosing cholangitis patients showed a similar T lymphocyte portal tract infiltrate. We conclude that a number of non-specific chronic inflammatory histological abnormalities were present in primary sclerosing cholangitis gall bladders. Immunohistochemistry found other features that were present in this disease - a predominantly lymphocytic mononuclear cell infiltrate of the superficial and deep layers of the gall bladder wall and the presence of T lymphocytes that infiltrated the biliary epithelial cells. These findings support the hypothesis that aberrant cell mediated immune mechanisms may play a role in the pathogenesis of both the intrahepatic and extrahepatic lesions in primary sclerosing cholangitis.

Adult↗
PubMed1992

Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.

The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction.

Adolescent↗
PubMed1993

Antineutrophil antibody: a test for autoimmune primary sclerosing cholangitis in childhood?

The detection of an antineutrophil antibody which is highly sensitive and specific for adult primary sclerosing cholangitis using indirect immunoalkaline phosphatase has been previously described. In this study, the diagnostic potential of this method in childhood primary sclerosing cholangitis is described. A range of 72 blinded children's sera (36 boys), aged six months to 21 years (10 primary sclerosing cholangitis, eight autoimmune chronic active hepatitis, 10 alpha-1 antitrypsin deficiency, 12 extrahepatic bile duct atresia, 11 ulcerative colitis and 21 normal subjects) was assayed. Eight of the 10 primary sclerosing cholangitis patients were correctly identified. Three patients with chronic active hepatitis also showed the characteristic primary sclerosing cholangitis pattern of staining. No ulcerative colitis patients or any other patients showed this pattern of staining. All normal subjects were negative. As in adult primary sclerosing cholangitis, there is a specific antineutrophil antibody in childhood primary sclerosing cholangitis and this provides further evidence towards an autoimmune aetiology of this condition. The test may have diagnostic potential.

Adolescent↗
PubMed1987

Risks of percutaneous transhepatic drainage in patients with cholangitis.

Percutaneous transhepatic biliary drainage (PTD) has been advocated as a method of achieving biliary decompression in patients with cholangitis. However, the risk of PTD in these patients has not been determined. Therefore, we reviewed the records of 95 consecutive PTD patients, 30 (32%) of whom had cholangitis. Forty-four (46%) of the 95 patients underwent PTD as a preoperative measure; the remaining 51 (54%) had PTD for palliation of end-stage malignancies. Thirty-day mortality and overall morbidity were 17% and 30%, respectively, in the patients with cholangitis and 15% and 28% in the patients without cholangitis. These differences were not statistically significant. However, patients with cholangitis had a significantly higher (p less than .05) incidence of post-PTD bacteremia. In patients undergoing PTD for palliation, both mortality (25%, p less than .01) and morbidity (35%) were higher than in those being drained preoperatively. This analysis suggests that PTD can be performed safely in patients with cholangitis and that the patient's underlying disease process is more important than the presence of cholangitis in determining the outcome.

Adolescent↗
PubMed2002

Comparison of MR cholangiopancreatographic techniques with contrast-enhanced cholangiography in the evaluation of sclerosing cholangitis.

OBJECTIVE: The purpose of our study was to compare MR cholangiopancreatography and contrast-enhanced cholangiography in patients with sclerosing cholangitis. MATERIALS AND METHODS: Twenty patients with sclerosing cholangitis were evaluated on MR cholangiopancreatography using the single-shot fast spin-echo technique at 1.5 T. A group of 19 healthy volunteers underwent MR cholangiopancreatography as controls. Thick-slab (2-cm sections) coronal oblique and thin-slab (5-mm sections) interleaved straight coronal MR images were obtained. All patients with sclerosing cholangitis had an MR cholangiopancreatogram within 12 months of a contrast-enhanced cholangiogram (mean, 3.8 months). Seventy-five percent of patients had an MR cholangiopancreatogram within 3 months of the contrast-enhanced cholangiogram. The MR cholangiopancreatograms and contrast-enhanced cholangiograms were reviewed independently in a random fashion by two radiologists who were unaware of clinical history for the degree of ductal visualization and for the presence and location of strictures of the intrahepatic and extrahepatic bile ducts. All discrepancies were resolved by a consensus, and the contrast-enhanced cholangiograms were regarded as the gold standard. Statistically significant data were calculated using the signed rank test (p < 0.01), and agreement analysis was calculated using Cohen's kappa. RESULTS: All findings on MR cholangiopancreatograms in healthy subjects were interpreted as normal, and all findings on MR cholangiopancreatograms in patients with sclerosing cholangitis were interpreted as abnormal. When compared with the control group, scans of patients with sclerosing cholangitis usually showed good visualization (>50%) of the intrasegmental (86% vs 9%) and peripheral (67% vs 0%) intrahepatic ducts on thick-slab MR cholangiopancreatography. Thick-slab MR cholangiopancreatography showed good visualization in more ducts than contrast cholangiography (84% vs 70%; p = 0.10) and showed more strictured ducts than contrast cholangiography (47% vs 36%; p = 0.22). When comparing those ducts with good visualization on both MR cholangiopancreatography and contrast cholangiography, we found that disagreement occurred regarding 32% of ducts. Most of the discrepancies (60%) resulted when a stricture was noted on MR cholangiopancreatography but not on contrast-enhanced cholangiography. Good interobserver agreement (kappa > 0.4) was noted for detecting strictures of the extrahepatic, left hepatic, left medial, and right posterior ducts, with the greatest agreement for extrahepatic ductal strictures (kappa = 0.8). CONCLUSION: Thick-slab MR cholangiopancreatography is the best technique for depicting normal and strictured bile ducts and allows the differentiation of healthy patients from patients with sclerosing cholangitis. Although endoscopic retrograde cholangiopancreatography was considered the standard, MR cholangiopancreatography was superior for intrahepatic biliary ductal visualization. Therefore, this technique is of value in the diagnosis and follow-up of patients with sclerosing cholangitis.

Adult↗
PubMed1985

Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts?

Review of liver biopsy specimens, autopsy specimens, and clinical records of 107 patients with chronic ulcerative colitis and hepatobiliary diseases showed "pericholangitis" (defined as small-duct primary sclerosing cholangitis) in 37 (35%), primary sclerosing cholangitis (defined as large-duct primary sclerosing cholangitis) in 18 (17%), chronic active hepatitis in 14 (13%), cryptogenic cirrhosis in 12 (11%), and miscellaneous lesions including malignancies in 26 (24%). Documented cirrhosis was present or developed in 37 patients (35%). The spectrum of histologic features of small-duct primary sclerosing cholangitis was indistinguishable from that of confirmed large-duct primary sclerosing cholangitis. In 6 of the 18 patients who eventually developed the large-duct disease, biopsy evidence 1 to 12 years earlier had shown small-duct primary sclerosing cholangitis. Thus, small-duct and large-duct primary sclerosing cholangitis seem to be components of a disease spectrum.

Bile Ducts, Intrahepatic↗
PubMed1988

Primary sclerosing cholangitis and celiac disease. A novel association.

The association of primary sclerosing cholangitis and celiac disease was observed in three patients, an association not previously reported. All three patients were men who presented with chronic cholestatic liver disease at ages 32, 46, and 62 years, respectively. In each patient, endoscopic retrograde cholangiography showed the typical findings of primary sclerosing cholangitis. Histologic features of liver biopsy were compatible with the diagnosis. Two patients had associated chronic ulcerative colitis. All three patients complained of frequent loose stools and weight loss; subsequent testing showed severe steatorrhea (204 to 323 mmol/d of fecal fat on a 100 g fat diet). Total villous atrophy was found in all three patients on histologic examination of the small bowel. Celiac disease was diagnosed at the time of presentation in two patients who had primary sclerosing cholangitis and was diagnosed three years after the onset of primary sclerosing cholangitis in the third patient. The celiac disease responded to a gluten-free diet in each patient whereas the primary sclerosing cholangitis was not affected by dietary treatment. The possibility of a chance association of primary sclerosing cholangitis and celiac disease cannot be accurately assessed but seems unlikely given the rarity of both diseases. The relationship between the two diseases remains unknown, although an immunologic connection is suspected. Celiac disease should be considered in the differential diagnosis of severe steatorrhea in patients with primary sclerosing cholangitis.

Adult↗
PubMed2000

[Effect of yinchen dandao decoction on plasma fibronectin, biliary thromboxane A2 and prostaglandin I2 in human and animal suffering from acute cholangitis].

OBJECTIVE: To study the therapeutic mechanism of Yinchen Dandao decoction (YCDDD) in treating acute cholangitis. METHODS: Twenty-four patients with acute cholangitis and 36 cholangiolithiasis patients were randomly classified into the treated group and the control group, and all of these patients had undergone surgical operation. The treated group were given orally YCDDD 3 days after operation for 1 week, and plasma fibronectin (FN), biliary thromboxane A2(TXA2) and prostaglandin I2(PGI2) were measured and compared before and after oral administration of the drug. The models of cholangitis were established in rabbits, which were also randomly grouped into the treated group and the control group, and the same parameters (FN, TXA2, PGI2) were observed as in rabbits. RESULTS: The level of FN was significantly lower in cholangitis patients than that in the cholangiolithiasis patients before operation (P < 0.01), and compared to the control group, it obviously raised after YCDDD treatment (P < 0.01), the same happened in the cholangiolithiasis patients. The value of TXA2 and PGI2 in the bile was obviously higher (P < 0.01, P < 0.05) in cholangitis patients than those in chlangiolithiasis, and obviously reduced after YCDDD administration (P < 0.01). The level of FN in the treated group and the level of biliary TXA2 and PGI2 in rabbits with cholangitis were significantly higher than those in the control group (P < 0.01). CONCLUSION: YCDDD caused the increase of FN and decrease of biliary TXA2 and PGI2, which might be one of the mechanisms of the drug carried out in cholangitis patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

[Management of cholangitis complicated in biliary carcinoma with hilar bile duct stenosis].

We reviewed 60 cases of biliary carcinoma with hilar bile duct stenosis which had received percutaneous transhepatic cholangio-drainage (PTCD). Of the 60 cases, nine were complicated with acute cholangitis (AC) and three with segmental acute obstructive suppurative cholangitis (S-AOSC). The incidence of cholangitis was 20%. Six patients with AC and three with S-AOSC underwent hepatic resection for carcinoma. As to preoperative management for cholangitis in these 9 cases, conservative chemotherapy was effective in only 2 cases, and additional PTCD or segmental introduction of the drainage catheter under PTCS were useful in 5 cases. The remaining 2 cases with S-AOSC needed urgent hepatic resection including suppurative hepatic segments after various interventional treatments. No significant difference was found in resectability, morbidity and mortality between the cholangitis group and non-cholangitis group. In conclusion, it is emphasized that postoperative outcome of biliary carcinoma with cholangitis will be improved by adequate PTCD and/or urgent hepatic resection.

Acute Disease↗
PubMed1991

Neutrophil cytoplasmic antibodies: a link between primary sclerosing cholangitis and ulcerative colitis.

Whether serum autoantibodies to neutrophil cytoplasmic components, previously found in ulcerative colitis, are also associated with primary sclerosing cholangitis was determined. In an enzyme-linked immunosorbent assay for immunoglobulin G neutrophil antibodies, neutrophil binding by primary sclerosing cholangitis sera was significantly greater than that for primary biliary cirrhosis, chronic hepatitis B, and chronic non-A, non-B hepatitis. Similar differences were seen when sera from patients with primary sclerosing cholangitis without evidence for ulcerative colitis were compared with sera from liver disease controls. Perinuclear immunofluorescence staining of neutrophils was exhibited by the majority of ulcerative colitis, primary sclerosing cholangitis, and primary sclerosing cholangitis without ulcerative colitis sera. The combination of elevated immunoglobulin G neutrophil antibodies and a perinuclear pattern was 65% sensitive and 100% specific for primary sclerosing cholangitis compared with the liver disease control sera. It is concluded that neutrophil cytoplasmic antibodies in ulcerative colitis and primary sclerosing cholangitis may be markers of shared underlying immunopathogenic mechanisms. Identification of the target antigen(s) may facilitate understanding of the underlying immune response and development of an improved disease marker assay.

Autoantibodies↗
PubMed1995

Biliary tract calculi in primary sclerosing cholangitis.

UNLABELLED: By conventional criteria the diagnosis of primary sclerosing cholangitis (PSC) is excluded if biliary tract calculi are present. OBJECTIVE: To compare patients with sclerosing cholangitis with and without calculi. METHODS: Retrospective review between 8/91 and 9/93 identified 63 patients with sclerosing cholangitis alone (Group A) and 22 patients with sclerosing cholangitis and biliary tract calculi (Group B). The mean follow-up was 13.6 months. Clinical features reviewed were age, sex, associated inflammatory disease (IBD), and clinical presentation. Cholangiographic features compared were site and extent of disease. Endoscopic stone extraction was reviewed for success and complications. RESULTS: Both groups had the following features in common: 1) mean age (45.9 vs 46.3 yr), 2) prevalence of IBD (68.3 vs 72.7%), 3) extent of bile duct strictures (intrahepatic: 28.5% vs 27.2%; extrahepatic: 12.7% vs 13.6%; both: 58.7% vs 54.5%). There were proportionately more women in Group B (45.5% vs 33.3%). Symptomatic presentation (pain, pruritus, jaundice, and cholangitis) was seen more often in Group B: 86.4% compared with Group A: 39.7% (specifically cholangitis was seen in 22.7% vs 4.7%). Among Group B, calculi developed subsequent (mean 40.2 months) after the diagnosis of sclerosing cholangitis in 77.3% of patients. The distribution of calculi was cholelithiasis: 7 (31.8%); choledocholithiasis: 9 (40.9%); and both: 6 (27.2%). Of the patients with choledocholithiasis alone, 78% had undergone previous cholecystectomy. Endoscopic stone extraction was successful in 13 (86.6%) of the patients with choledocholithiasis. Complications included mild pancreatitis in one patient and bleeding from sphincterotomy site in another patient which responded to sclerotherapy. In follow-up, only one patient had recurrent calculi and underwent successful stone extraction. CONCLUSION: We suggest that biliary tract calculi are a part of the spectrum of otherwise typical PSC and therefore their presence should not necessarily exclude the diagnosis.

Adult↗
PubMed1998

Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II.

Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have been reported to have serum antibodies to CA-II. Moreover, active immunization of susceptible mice with CA-II results in inflammation of submandibular glands, where CA-II is also expressed. In the present study, we attempted to produce cholangitis by immunization with CA-II using two strains of mice with different potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of human CA-II (100 microg) intraperitoneally every other week on three occasions. One week after the final immunization, mice were killed and blood and tissue samples harvested. Light and electron microscopic evaluation for inflammation was performed under coded identification. After immunization of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between cholangiocytes was also seen. Inflammation was not observed outside the liver. Morphologic evidence of cholangitis was observed in 8 (53.3%) of 15 Balb/c mice and in 3 (20%) of 15 DBA/1 J mice. In the control mice immunized with bovine serum albumin (BSA), cholangitis was observed in only 1 (6.7%) of 15 Balb/c mice and none of 15 DBA/1J mice. Balb/c mice immunized with CA-II had statistically significant cholangitis compared with those immunized with BSA (p < 0.01), whereas DBA/1J did not show a significant difference from controls. Balb/c mice immunized with CA-II showed specific antibody production after immunization, whereas DBA/1J mice immunized with CA-II had anti-CA-II antibody even in preimmune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/c mice resulted in cholangitis in two (66.7%) of three Balb/c recipients. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.

Adoptive Transfer↗
PubMed1991

Late cholangitis after successful surgical repair of biliary atresia.

Bacterial cholangitis is a frequent complication of successful surgical repair of biliary atresia, occurring in 93% of patients before the age of 1 year, but thought to be rare after 2 years of age. Among 76 children free of jaundice more than 5 years after operation, four presented with late cholangitis (7 to 13.5 years old), consisting of fever, jaundice, and abdominal pain with biochemical features of an inflammatory process and cholestasis. Liver biopsy specimens consistently demonstrated histological features of cholangitis, growth of microorganism, or both. Cholangitis subsided spontaneously in one patient or in response to intravenous administration of antibiotics. Cholangiography consistently demonstrated biliary abnormalities but no definite obstruction to the bilioenteric anastomosis. All the children had good hepatic function 3 weeks to 4 years after the episode of cholangitis. These results suggest that cholangitis may occur several years after surgery but does not seem to alter prognosis.

Acute Disease↗
PubMed2001

Management of gallstone cholangitis in the era of laparoscopic cholecystectomy.

HYPOTHESIS: The combined endoscopic and laparoscopic approach is safe and effective in managing gallstone cholangitis in the era of laparoscopic cholecystectomy (LC). DESIGN: Retrospective case series. SETTING: University teaching hospital. PATIENTS: One hundred eighty-four consecutive patients with gallstone cholangitis treated between January 1995 and December 1998. INTERVENTIONS: The main treatments were endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) followed by interval LC. Open or laparoscopic common bile duct exploration (OCBDE or LCBDE) was used when ERCP or ES failed. MAIN OUTCOME MEASURES: Success of various interventions, morbidity and mortality, and long-term incidence of recurrent biliary symptoms. RESULTS: Endoscopic retrograde cholangiopancreatography was successful in 175 patients (95%), with bile duct stones found in 147 (84%). Endoscopic stone clearance by ES was achieved in 132 patients (90%). Morbidity rate after ERCP or ES was 4.0% (n = 7), and overall mortality rate from cholangitis was 1.6% (n = 3). After bile duct stone clearance, 82 patients underwent LC with a conversion rate of 9.8% (n = 8) and a morbidity rate of 3.6% (n = 3). Eighteen patients underwent OCBDE with a morbidity rate of 33% (n = 6), and 3 underwent LCBDE with 1 conversion and no morbidity. There was no operative mortality. Seventy-eight patients were managed conservatively after endoscopic clearance of bile duct stones. Follow-up data were available in 101 patients with cholecystectomy and 73 patients with gallbladder in situ. During a median follow-up of 24 months, recurrent biliary symptoms occurred in 5.9% (n = 6) and 25% (n = 18), respectively (P =.001). In both groups, the most common recurrent symptom was cholangitis (n = 5 and n = 14, respectively). Gallbladder in situ (risk ratio, 4.16; 95% confidence interval, 1.39-12.50; P =.01) and small-size papillotomy (risk ratio, 2.94; 95% confidence interval, 1. 07-8.10; P =.04) were significant risk factors for recurrent biliary symptoms. CONCLUSIONS: Endoscopic sphincterotomy for biliary drainage and stone removal, followed by interval LC, is a safe and effective approach for managing gallstone cholangitis. Patients with gallbladder left in situ after ES have an increased risk of recurrent biliary symptoms. Laparoscopic cholecystectomy should be recommended after endoscopic management of cholangitis except in patients with prohibitive surgical risk.33333333333333333333333

Acute Disease↗
PubMed2000

Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are presumed autoimmune chronic cholestatic liver diseases characterized by cholangitis and progressive loss of bile ducts. Cytokines have been postulated to be involved in the progression of these diseases, but their role is poorly defined. Our objectives were to characterize a rat model of cholangitis and to determine Type 1/Type 2 (Th1/Th2) cytokine profile shifts in this model. Cholangitis was induced in Sprague-Dawley rats (200 to 225 g) by low-dose oral administration of the biliary toxin alpha-naphthylisothiocyanate (ANIT) (1 g/kg powdered rat chow ad libitum) for 4, 7, and 14 days. Cholestasis was observed in ANIT-treated animals. Liver histology of ANIT-treated rats showed hepatic inflammation centered on damaged bile ducts, significant bile duct proliferation, and progressive fibrosis. Immunohistochemistry showed enhanced staining of hepatic major histocompatibility complex (MHC) II, CD4, and CD8 in portal areas of ANIT-treated animals. In addition, the hepatic cytokine profile became increasingly Th1 in nature with progressive ANIT treatment. In summary, experimental cholangitis biochemically and histologically mimics human chronic cholangitis and furthermore, is associated with a progressive shift to a more Th1-dominant hepatic cytokine profile. Therefore, this model may be useful for examining the role of cytokines in the progression of chronic cholangitic diseases.

Animals↗
PubMed1995

Colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.

PURPOSE: Most patients with primary sclerosing cholangitis also have ulcerative colitis. It has been suggested that in the presence of primary sclerosing cholangitis the risk of colorectal dysplasia and carcinoma is greater than in patients with ulcerative colitis alone. METHODS: In a retrospective study, we evaluated the possibility of colorectal cancer or dysplasia in 35 consecutive patients with primary sclerosing cholangitis and ulcerative colitis seen at The Johns Hopkins Hospital between 1979 and 1991. RESULTS: Thirteen of the 35 patients (37 percent) with ulcerative colitis and primary sclerosing cholangitis had colorectal neoplasia (5 with adenocarcinoma and 8 with dysplasia). In the 27 patients undergoing colonoscopic biopsy surveillance, the cumulative incidence at 28 years of colorectal cancer was 18.5 percent and for colorectal dysplasia it was 29.6 percent. The high incidence of colorectal cancer was less than the rate of colorectal cancer in patients with extensive colitis of childhood onset without primary sclerosing cholangitis (35 percent), but the rate of colorectal cancer and dysplasia (48.1 percent) is similar to the highest rates of cancer noted in the comparison group. Because patients had subtle, quiescent colitis, a short time from diagnosis of ulcerative colitis to diagnosis of colorectal neoplasia was noted (mean, 12.2 +/- 9 years; less than 8 years in 5/13 (38.5 percent) patients). CONCLUSION: Ulcerative colitis patients with primary sclerosing cholangitis appear to have a high frequency of colorectal cancer but a rate lower than expected in patients with extensive quiescent ulcerative colitis of childhood onset alone. However, exact conclusions are complicated by the high incidence of colorectal dysplasia found, which portends malignant transformation. Because of the subtle nature of colitis, the diagnosis of ulcerative colitis is often delayed, and surveillance programs should start as soon as ulcerative colitis is diagnosed.

Adenocarcinoma↗
PubMed2001

Proximal colorectal dysplasia or cancer in ulcerative colitis. The impact of primary sclerosing cholangitis and sulfasalazine: results from a 20-year surveillance study.

PURPOSE: Known risk factors for the development of colorectal dysplasia or cancer in ulcerative colitis are total colonic involvement and long duration of the disease. It has recently been suggested that presence of primary sclerosing cholangitis is another independent risk factor-especially for proximal colorectal dysplasia or cancer-and that treatment with sulfasalazine might reduce the frequency of colorectal cancer in ulcerative colitis; the present study was undertaken to shed light on the validity of these theories. METHODS: A total of 143 patients with ulcerative colitis underwent regular colonoscopies and multiple biopsies in a 20-year surveillance program for studies of long-standing total ulcerative colitis. Fifty-one of the patients developed colorectal dysplasia or cancer. Patient records were scrutinized retrospectively for information of presence of primary sclerosing cholangitis, site of the colorectal malignancy, and results of sulfasalazine treatment. RESULTS: Nineteen of the patients had primary sclerosing cholangitis; these ran a significantly higher risk of developing colorectal dysplasia or cancer than patients with ulcerative colitis only. All colorectal cancers (n = 3) and 75 percent of all colorectal dysplasias or cancers among patients with primary sclerosing cholangitis were located in the proximal part of the colon, whereas 36 percent were found in that same region among the patients with ulcerative colitis without primary sclerosing cholangitis (P = 0.02). Sulfasalazine treatment showed no significant protective effect on the development of colorectal dysplasia or cancer in patients with ulcerative colitis. CONCLUSION: The risk evaluation, as assessed by multivariate analysis, shows that primary sclerosing cholangitis proves to be an additional and independent risk factor for the development of colorectal dysplasia or cancer in patients with ulcerative colitis-particularly in the proximal part of the colon. The findings do not support the theory that sulfasalazine treatment exerts a protective effect against colorectal dysplasia or cancer.

Adult↗