Airway involvement in ulcerative colitis

Two patients with ulcerative colitis developed progressive obstructive pulmonary disease. In one, the abnormality was a sclerosing peribronchiolitis confined to small airways, while the other demonstrated a large airway fibrotic obliterative bronchitis. A review of airway involvement in ulcerative colitis and a discussion of the possible similarity to another extraintestinal manifestation of ulcerative colitis, sclerosing cholangitis, are presented.     

Surgical Management of Ulcerative Colitis in the Presence of Primary Sclerosing Cholangitis

INTRODUCTION: The surgical management of ulcerative colitis in the patient with primary sclerosing cholangitis is controversial. METHODS: This study was designed as a retrospective chart review of all patients with primary sclerosing cholangitis who were surgically treated for ulcerative colitis. RESULTS: Sixteen patients with primary sclerosing cholangitis and ulcerative colitis were identified. The indication for ulcerative colitis surgery was dysplasia in 7 patients (44 percent), cancer in 2 (13 percent), intractability in 4 (25 percent), and unknown in 1. Final colon pathology demonstrated cancer in three patients and dysplasia in four. Two patients had biliary cancer discovered at the time of orthotopic liver transplantation. Thirteen patients were known to have primary sclerosing cholangitis when they underwent surgery for ulcerative colitis; two patients with severe primary sclerosing cholangitis underwent simultaneous orthotopic liver transplantation/total abdominal colectomy and did well with subsequent ileal pouch reconstruction. Two patients had orthotopic liver transplantation first and then ileal pouch-anal anastomosis (1 patient) or total abdominal colectomy (1 patient) and did well. Seven patients had well-controlled primary sclerosing cholangitis on medication and underwent ileal pouch-anal anastomosis or total abdominal proctocolectomy without significant hepatic compromise. One patient with moderate primary sclerosing cholangitis underwent ileorectal anastomosis and had severe liver failure postoperatively but survived. Another patient with worsening primary sclerosing cholangitis after total abdominal colectomy has since developed persistent bleeding from peristomal varices. CONCLUSIONS: The overall cancer/premalignant lesion rate was high (50 percent in this study) in patients with primary sclerosing cholangitis and ulcerative colitis. Complications associated with the surgical management of ulcerative colitis are largely dictated by the degree of liver disease present at the time of surgery. Patients with significant primary sclerosing cholangitis that requires colectomy can undergo simultaneous orthotopic liver transplantation/total abdominal colectomy and then be candidates for subsequent ileal pouch-anal anastomosis reconstruction once liver function has improved. Patients with well-controlled primary sclerosing cholangitis can undergo ileal pouch-anal anastomosis surgery safely.     

The course of colonic disease in ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND/AIMS: Although there are many studies reporting that colonic dysplasia and cancer develop more frequently in ulcerative colitis patients with ulcerative colitis with primary sclerosing cholangitis, there are insufficient data on the course of the colonic disease. In this study, the course of the colonic disease in ulcerative colitis patients with primary sclerosing cholangitis was investigated. METHODS: Data obtained from ten patients with total colitis and accompanying primary sclerosing cholangitis (three females, seven males, mean age: 44.5+/-10.0 years) were compared with data obtained from 64 patients with pancolitis but without primary sclerosing cholangitis (27 females, 37 males; mean age: 42.3+/-17.1 years). RESULTS: The follow-up period was 6.4+/-6.2 years in patients without primary sclerosing cholangitis, 12.7+/-6.2 years in total and 5.1+/-4.0 years (after development of the condition) in patients with primary sclerosing cholangitis (p<0.01). The number of disease attacks (3.7 attacks/yr vs. 0.5 attacks/yr), duration of the active disease (12.9+/-8.0 months vs. 0,3+/-1.0 months), the number of patients in whom corticosteroids were used (47 patients vs. one patient), the number of patients hospitalized (50 patients vs. one patient) and duration of hospitalization (1.2+/-0.8 months vs. 0,1+/-03 months) were higher in patients with than without primary sclerosing cholangitis (after development of the condition) (p<0.001). There was no significant difference in data obtained from patients with and without primary sclerosing cholangitis before development of the disease. CONCLUSIONS: Colonic disease subsides when primary sclerosing cholangitis develops. The higher frequency of colonic dysplasia and cancer seen in patients with primary sclerosing cholangitis can be explained by the fact that most of them have a longer duration of total colitis and fewer need total colectomy. Even though it does not seem to cause clinical problems, the colonic disease should not be ignored in these patients.     

Three cases of primary sclerosing cholangitis associated with ulcerative colitis; diagnostic usefulness of magnetic resonance cholangiopancreatography

BACKGROUND/AIMS: Primary sclerosing cholangitis is often accompanied by inflammatory bowel disease in western countries. However, the incidence of primary sclerosing cholangitis in patients with ulcerative colitis appears to be much lower in Japan. METHODOLOGY: Between 1980 and 1998, a total of 402 patients with ulcerative colitis were seen in our department. The patients were evaluated by abdominal ultrasonography, endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography when persisting abnormalities of biochemical findings suggested the presence of hepatobiliary diseases. RESULTS: Of the 402 patients with ulcerative colitis, 3 patients with primary sclerosing cholangitis were found. There were 2 men and 1 woman. One patient had left-sided colitis while 2 had total colitis. Magnetic resonance cholangiopancreatography was done in 2 of these 3 patients and demonstrated diagnostic features of primary sclerosing cholangitis. All 3 patients had intra- and extrahepatic involvement by primary sclerosing cholangitis. One male patient died due to progressive hepatic failure. The other male patient was treated with ursodeoxycholic acid, but serum alkaline phosphatase level remained above the normal range. The female patient maintained normal serum alkaline phosphatase levels without specific medication. CONCLUSIONS: Magnetic resonance cholangiopancreatography is the most safe and convincing tool for the diagnosis of coexistent primary sclerosing cholangitis in the patients with ulcerative colitis.     

Association of primary sclerosing cholangitis,ulcerative colitis and coeliac disease in female siblings

Primary sclerosing cholangitis is a rare, cholestatic liver disease, most commonly affecting young men. The association of primary sclerosing cholangitis with other autoimmune disorders, although rare, indicates a genetic predisposition for this disease. We describe, for the first time, the association of primary sclerosing cholangitis, ulcerative colitis and coeliac disease in two sisters. Ulcerative colitis was mild and preceded liver disease in both patients. There were no symptoms of coeliac disease, and its silent form was diagnosed on the basis of serological tests. Both patients carried HLA molecules DR3 and DQ2. Although HLA DR4 was not found, there was a rapid progression of liver disease to cirrhosis and cholangiocarcinoma in one patient. The familial occurrence of primary sclerosing cholangitis, ulcerative colitis and coeliac disease supports the hypothesis of genetic predisposition for these diseases.     

Atrophy and Neoplastic Transformation of the Ileal Pouch Mucosa in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

INTRODUCTION: Patients with ulcerative colitis and primary sclerosing cholangitis have an increased risk of developing carcinoma both in the bile ducts and in the colon. PURPOSE: To investigate whether this patient group also has an increased risk of developing atrophy and neoplasia in the ileal pouch mucosa after construction of a pelvic pouch with an ileoanal anastomosis or a continent Kock ileostomy. METHODS: Flexible video endoscopic examinations of the ileal pouch were performed in 16 patients with ulcerative colitis and primary sclerosing cholangitis and in 16 matched patients with ulcerative colitis without sclerosing cholangitis. Biopsies were sampled from different locations in the pouch for histologic assessment of mucosal atrophy and dysplasia and for flow cytometric DNA analysis assessing chromosomal aberrations. RESULTS: The patients with sclerosing cholangitis developed moderate or severe atrophy in the pouch significantly more often (P < 0.01). Persistent severe mucosal atrophy was revealed in eight patients with sclerosing cholangitis and only in two controls. One patient with sclerosing cholangitis had high-grade dysplasia in multiple locations. Low-grade dysplasia was assessed in three patients with sclerosing cholangitis and in two of the controls. DNA aneuploidy was displayed in three patients, all with sclerosing cholangitis and dysplasia. All patients with neoplastic transformation had a pouch with ileoanal anastomosis and a long pouch duration (> 8 years). CONCLUSION: Patients with ulcerative colitis and primary sclerosing cholangitis with an ileal reservoir are more prone to developing mucosal atrophy in the pouch and seem to have a higher risk of neoplastic transformation in the pouch mucosa than patients with ulcerative colitis without sclerosing cholangitis.     

Primary sclerosing cholangitis. A report of nine cases and clinical review.

Nine cases of primary sclerosing cholangitis were reviewed as to methods of diagnosis, association with other disease states and clinical course of the patients. There were four cases of primary sclerosing cholangitis occurring alone, four cases associated with inflammatory bowel disease (three with chronic ulcerative colitis and one case with proctosigmoiditis) and one case associated with porphyria cutanea tarda. All cases of primary sclerosing cholangitis occurring alone, progressed to secondary biliary cirrhosis, however, none of the cases associated with chronic ulcerative colitis progressed to secondary biliary cirrhosis. In all cases, the diagnosis was established by operative findings and biopsy results. The mode of clinical presentation was similar in all cases and was characterized by slowly progressive jaundice. Intravenous and oral cholangiography were not useful in establishing a diagnosis but endoscopic retrograde cholangiography offers preoperative diagnostic hope and use for follow-up evaluation. One case with ulcerative colitis had a Strongyloides infection and the organism was found in the fibrotic duct and pericholedochal lymph nodes. The etiological considerations are reviewed and the classification of sclerosing cholangitis associated with ulcerative colitis, as primary, is discussed. Therapeutic modalities are discussed, though therapy is mainly empirical at present.     

Primary sclerosing cholangitis, ulcerative colitis and type 1 diabetes mellitus]

Primary sclerosing cholangitis is a cholestatic disease of unknown origin. Occasionally, this disease is combined with different of probable autoimmune genesis, particularly with ulcerative colitis (> 50%). The reported case describes the rare subsequent development of primary sclerosing cholangitis, ulcerative colitis and insulin-dependent diabetes mellitus (IDDM) in a 22-year-old male patient. The coincidence of primary sclerosing cholangitis and IDDM supports the assumption of common factors in the etiopathogenesis of both diseases.     

Pouchitis Disease Course after Orthotopic Liver Transplantation in Patients with Primary Sclerosing Cholangitis and an Heal Pouch-Anal Anastomosis

Objective: Primary sclerosing cholangitis is associated with the development of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. This study determined the effect of liver transplantation for primary sclerosing cholangitis on the disease course of pouchitis.
Methods: Seven patients with an ileal pouch-anal anastomosis for ulcerative colitis underwent liver transplantation for primary sclerosing cholangitis. The medical record was reviewed to determine the pouchitis activity and pattern (no pouchitis, single acute, recurrent acute, chronic) before and after transplantation.
Results: Five of seven patients had pouchitis before transplant [recurrent acute (n = 3), chronic (n = 2)], and four of those five continued to have pouchitis after transplant (all chronic). Pretransplant sera were positive for antineutrophil cytoplasmic antibody in 6/6 patients, compared to 5/6 patients posttransplant. One patient with pouchitis pre-transplant became negative for antineutrophil cytoplasmic antibody posttransplant but continued to have pouchitis.
Conclusion: Pouchitis occurs frequently in patients with primary sclerosing cholangitis and an ileal pouch-anal anstomosis for ulcerative colitis. Liver transplantation does not alter the disease course of pouchitis for most of these patients.     

Symptomatic chronic calcific pancreatitis in a patient with idiopathic ulcerative colitis and sclerosing cholangitis.

Although sclerosing cholangitis is well recognized to occur in patients with idiopathic inflammatory bowel disease, pancreatitis as a complication of ulcerative colitis is uncommon. We describe a patient who had idiopathic ulcerative colitis, primary sclerosing cholangitis and calcific pancreatitis with endocrine pancreatic deficiency, a rare combination.     

Does primary sclerosing cholangitis occurring in association with inflammatory bowel disease differ from that occurring in the absence of inflammatory bowel disease? A study of sixty-six subjects

Primary sclerosing cholangitis often occurs in association with inflammatory bowel disease, particularly ulcerative colitis but also Crohn's disease of the colon either with or without terminal ileal disease. Little data exist as to the effect of inflammatory bowel disease on the presenting symptoms, radiological features, response to liver transplantation, and potential risk of bile duct carcinoma in individuals with primary sclerosing cholangitis. In an effort to answer these questions, 66 patients with primary sclerosing cholangitis were studied. The definitive diagnosis of primary sclerosing cholangitis in each was accomplished using cholangiography, which in each case demonstrated characteristic beading, ectasia and stricturing of the intrahepatic and extrahepatic bile ducts. Inflammatory bowel disease was present in 47 (71.2%) patients. Thirty nine (59.1%) had ulcerative colitis; their mean age was 42.5 +/- 11.6 yr (mean +/- SD), and the male/female ratio was 2.9:1. In addition, eight patients (12.1%) had Crohn's colitis; their mean age was 40.5 +/- 6.5 yr, and the male/female ratio of this group was 1:1. Nineteen patients (28.8%) had primary sclerosing cholangitis without any inflammatory bowel disease; their mean age was 42.0 +/- 12.1 yr, and the male/female ratio in this group was 0.72:1. Seventy-two percent of the patients without inflammatory bowel disease had either jaundice, pruritus or fatigue at presentation compared with 41% of the patients with inflammatory bowel disease (p less than 0.05). In contrast, abnormal liver function tests were more common as the first manifestation of liver disease in the latter group (38% vs. 11%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis,primary sclerosing cholangitis,and Crohn's disease.

Fifty two serum samples from patients with Crohn''s disease, 24 from patients with ulcerative colitis, and 12 from patients with primary sclerosing cholangitis were analysed for the presence of anti-neutrophil cytoplasm antibodies (ANCA) of IgG and IgA class by means of enzyme linked immunosorbent assays using lactoferrin, myeloperoxidase, and antigen extracted from azurophil granules, ''alpha antigen'' (that is, an antigen preparation containing proteinase 3) as substrates. A high frequency of positive tests for IgG anti-lactoferrin antibodies was found in sera from patients with ulcerative colitis (50%) and primary sclerosing cholangitis (50%). In Crohn''s disease only 4 of 52 (8%) sera had anti-lactoferrin antibodies--in all four instances the sera belonged to patients with disease involving the colon. All patients with sclerosing cholangitis and positive tests for anti-lactoferrin had ulcerative colitis. Low levels of IgG antibodies against myeloperoxidase or alpha antigen were also found occasionally in sera from patients with ulcerative colitis and primary sclerosing cholangitis. IgA antibodies directed against lactoferrin and alpha antigen (but not myeloperoxidase) were seen in all three conditions.     

Antibodies to colonic epithelial cells from the serum and colonic mucosal washings in ulcerative colitis.

It has been suggested that antibodies to a colonocyte protein of 40 kD (an intestinal isoform of tropomyosin) are specifically found in the serum and mucosa of patients with ulcerative colitis, which has important pathogenic implications. This study isolated and purified tropomyosin from the colonic mucosa, but no specific binding to this protein has been detected in serum samples or immunoglobulins isolated from mucosal washings of 20 ulcerative colitis (UC) patients by enzyme linked immunosorbent assay (ELISA) compared with 21 controls or 17 Crohn's disease (CD) patients. Samples from a further 12 patients with UC and primary sclerosing cholangitis (it is proposed that cross reactivity against the intestinal tropomyosin isoform accounts for the extraintestinal disease) also did not show binding to tropomyosin, whereas monoclonal antitropomyosin antisera bound both ELISAs and western blots. This study also examined the proteins in the normal colonic biopsy specimens on western blots that are bound by both serum samples and mucosal immunoglobulin preparations from these patients groups; there was no specific IgG or IgA binding to patients with UC or UC/primary sclerosing cholangitis, whereas binding to mitochondrial proteins of 70,000 and 45,000 was seen in samples from 12 primary biliary cirrhosis positive controls. This work does not support the hypothesis that autoimmune activity against the intestinal isoform or tropomyosin is important in the pathogenesis of ulcerative colitis.     

NASAL MUCOSAL INVOLVEMENT IN ULCERATIVE COLITIS

Abstract: :A patient with ulcerative colitis, sclerosing cholangitis, and mouth ulceration, developed an unusual lesion involving the nasal mucosa. This was thought to represent another extra-intestinal manifestation of inflammatory bowel disease.     

Peristomal varices after proctocolectomy in patients with primary sclerosing cholangitis

Primary sclerosing cholangitis is a chronic cholestatic liver disease that is commonly associated with chronic ulcerative colitis. We observed the development of varices in the abdominal wall surrounding the ileostomy stoma of patients with primary sclerosing cholangitis who underwent proctocolectomy and ileostomy for chronic ulcerative colitis. In 10 of 19 patients, the development of peristomal varices was documented 12-133 mo after operation. Risk factors for the development of peristomal varices included splenomegaly, esophageal varices, advanced histologic stage at liver biopsy, low serum albumin, thrombocytopenia, and an increased prothrombin time. Recurrent bleeding from peristomal varices was a major problem; 7 of 10 patients required repeated blood transfusions. The only therapy of long-term benefit was surgical decompression of the portal venous system in 1 patient and liver transplantation in a second patient. In contrast, there was no perirectal bleeding in 4 patients with primary sclerosing cholangitis who underwent proctocolectomy with an ileoanal anastomosis.     

Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.     

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.     

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon- after purified protein derivative stimulation (P<0.02). More cells secreting interferon- were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P<0.03). The number of cells secreting interferon- in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P<0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P=0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.This study was supported by grants from The Swedish Medical Research Council (7129), foundations of the Karolinska Institute, the Nanna Svartz foundation, the Swedish Society of Medicine, and the Ruth and Richard Juhlin foundation.     

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.