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Intermittent jaundice and rigors in a patient with longstanding ulcerative colitis

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Q1: What does the PTC (fig 1; see p 406) show and given the history of ulcerative colitis what is the most likely diagnosis?

The PTC shows strictures, dilatation, and irregularity of the intrahepatic ducts, with little or no flow of contrast into the common hepatic duct. The features are suggestive of primary sclerosing cholangitis (PSC) in this patient with long standing ulcerative colitis. With apparent obstruction at the porta hepatis, the differential diagnosis must include a cholangiocarcinoma complicating PSC.

Estimates of the prevalence suggest PSC to be present in 2.4–7.5% of patients with ulcerative colitis and approximately two thirds of patients with PSC have an underlying inflammatory bowel disease confirming a strong association between the two conditions. PSC is commoner in young males, but affects all age groups. Several HLA haplotypes, including HLA-B8, HLA-DR2, HLA-DR3 and HLA-Dw52A, have been linked with the condition and its association with other autoimmune conditions suggests immunological attack plays an important part in the pathogenesis. It may predate colitic symptoms or, as in this case, be seen to complicate established colitis. Symptoms of colitis in patients with PSC are often few or absent, the disease seems to run a milder course than in patients with ulcerative colitis without PSC or even be subclinical. In one series, seven out of nine patients diagnosed with PSC but with no obvious symptoms of colitis who went on to have colonoscopy had histological evidence of colitis.1 Both intrahepatic and extrahepatic ducts can be involved in the inflammation and fibrosis which characterises PSC. This leads to strictures and localised dilatation within these ducts. There is a 15%–20% cumulative life risk of developing a cholangiocarcinoma and the risk of developing carcinoma of the gallbladder is also increased. Choledocholithiasis may complicate PSC. Patients presenting with calculi share the same epidemiological features, extent of radiological changes, HLA typing and risk of malignancy as PSC patients not presenting with calculi.2 Most patients with calculi are symptomatic at presentation and recurrent episodes of ascending cholangitis are not uncommon. This is the likely cause of the initial presenting symptoms and operative findings in this case.

Q2: What is the connection between this hepatological diagnosis and the findings of dysplasia at colonoscopy?

The subset of patients with ulcerative colitis and PSC seem to be at even greater risk of developing colorectal dysplasia and cancer than other patients with pancolitis. The clearest evidence for this is a large case-control study comparing this subgroup with matched controls with ulcerative colitis but no PSC. This suggested a threefold risk of developing colorectal cancer or dysplasia over and above the control group.3 Previous studies had provided conflicting evidence due to small sample size, referral bias, failure to adequately match cases and controls in terms of disease duration, and extent or their maintenance treatment leading to overestimation of the risk. PSC as a risk factor for the development of colonic cancer or dysplasia in patients with ulcerative colitis is therefore probably independent of the risk conferred by longstanding total colitis. This question of additional risk to ulcerative colitis patients with PSC is of some importance when considering colonic surveillance, especially as patients with ulcerative colitis and PSC may have had subclinical colitis for several years before developing colitic symptoms. With a cumulative risk of colorectal cancer at 10 years of up to 25% in this group, annual colonoscopic screening has been recommended. The patient had low grade dysplasia within a raised lesion in the context of ulcerative colitis. This has been termed a dysplasic associated lesion or mass (DALM). Evidence suggests that upto 40% of such cases will already have a cancer within the colon and that they should undergo colectomy.4

Q3: Given the deteriorating liver function tests, computed tomography findings, and colonoscopic changes how would you manage this case?

The progressive, non-fluctuating rise in bilirubin level, in the absence of sepsis, coupled with the signs of decompensated liver cirrhosis suggest progression to end stage liver failure. Optimal timing for transplant in PSC patients has not been clearly defined and early referral is recommended. Referral should be made if there is a non-fluctuating increase in serum bilirubin (>100 μmol/l), significant impairment of synthetic liver function ensues, of if life threatening complications of decompensated cirrhosis develop (for example, spontaneous bacterial peritonitis, variceal bleeding, encephalopathy).5 Prognostic models have been developed in an attempt to guide clinicians as to timing of referral to the transplant centre. These are based on clinical and biochemical parameters correlating with prognosis on multivariate analysis of retrospective clinical series of PSC patients. However, clinical models which apply to populations have wide confidence intervals when applied to individuals and care needs to be taken not to become over-reliant on such scoring systems.5 None of these clinical or laboratory parameters predict the development of cholangiocarcinoma, the most serious complication of PSC, which may preclude curative treatment by orthotopic liver transplant (OLT). Further investigation of the cystic mass lesion in this patient showed no evidence of cholangiocarcinoma.

In this patient, the presence of low grade colonic dysplasia within a raised lesion (DALM) is worrying and suggests he requires colectomy due to the high risk that cancer has already developed in his colon. Furthermore, the risk of developing a subsequent colonic cancer has been shown to be increased further in those patients with PSC and ulcerative colitis who retain their colon after OLT and who then require long term immunosuppression.

Given the combination of end stage liver failure secondary to PSC and the need for surgical management of the colonic dysplasia the patient was transferred to Queen Elizabeth Hospital, Birmingham. Three management strategies were possible: (1) colectomy following OLT at a later date, (2) OLT followed by colectomy at a later date, or (3) a combined procedure. Colectomy followed by OLT in the context of such deteriorating liver function would not be an option as it would carry a very high mortality rate. OLT with colectomy at a later date is not ideal as there is a high risk of colonic cancer already having developed which, in theory at least, may be potentiated by post-OLT immunosuppression. Despite the potential additional morbidity and risk of postoperative infection carried by the combined procedure this was the preferred option. The possibility of discovery of a cholangiocarcinoma at operation which would preclude OLT was explained to the patient. The combined procedure was successful and he made a full recovery. There was no evidence of tumour in either liver or colonic resection specimens. He remains well on standard immunosuppression four years later.

Final diagnosis

Decompensating cirrhosis and colonic dysplasia complicating primary sclerosing cholangitis and ulcerative colitis.

References

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