Endoscopic Retrograde Cholangiopancreatography in the Diagnosis of Jaundice Associated with Ulcerative Colitis

GASTROENTEROLOGY

Copyright© 1974

67:907- 911, 1974

Vol. 67, No.5

by The Williams & Wilkins Co.

Printed in U.S.A .

ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN THE DIAGNOSIS OF JAUNDICE ASSOCIATED WITH ULCERATIVE COLITIS E.

ELIAS,

J . A.

SuMMERFIELD,

R.

DicK, AND S . SHERLOCK

Departments of Medicine and Radiology, Royal Free Hospital , London, England

Jaundice occurs in patients with ulcerative colitis for several reasons. By performing endoscopic retrograde cholangiopancreatography in 4 such patients we have excluded extrahepatic obstruction in 1. Of the other 3 patients, 2 were shown to have multiple strictures affecting the extra- and intrahepatic tree, indicating advanced sclerosing cholangitis, and surgery has not been attempted . In the other patient, a short irregular stricture was shown at subsequent operation to be a cholangiocarcinoma and was resected. Endoscopic retrograde cholangiopancreatography is of particular value in jaundiced patients with ulcerative colitis, not only in demonstrating extrahepatic obstruction when present, but also in showing whether surgical intervention is likely to benefit the patient. Thus patients with features of cholestasis may be spared liver biopsy, unsuccessful percutaneous transhepatic cholangiography, and hazardous biliary surgery.

Patients with ulcerative colitis have an increased incidence of several forms of hepatobiliary disease. These include fatty change, 1 pericholangitis, 2 chronic active hepatitis, 3 cryptogenic cirrhosis, 3 primary sclerosing cholangitis, 4 • 5 cholangiocarcinoma, 6 and carcinoma of the gallbladder. 7 When cholestasis predominates, it is often difficult to exclude obstructive lesions which would benefit from surgery. We have found endoscopic retrograde cholangiopancreatography (ERCP) of value in the differential diagnosis of jaundiced patients with ulcerative colitis and would like to report our experience in 4 illustrative cases. Materials and Methods The examination was performed on inpatients in the X-ray department. Patients were Received February 5, 1974. Accepted May 2, 1974. Address requests for reprints to: Dr. E. Elias, Department of Medicine, Royal Free Hospital, Gray's Inn Road, London, WClX 8LF, England. Dr. Summerfield was supported by a Medical Research Council Clinical Research Fellowship. The authors wish to thank Dr. W. B. Young for his helpful comments and advice.

fasted for 6 hr and given intramuscular premedication with atropine (0.6 mg) and amylobarbitone sodium (125 to 250 mg). The pharynx was anesthetized by two amethocaine (2Dimethylaminoethyl p-butylaminobenzoate) (tetracaine NF) lozenges. The patients were intubated in the left lateral position. Diazepam was given intravenously immediately before intubation. Hyoscine-N-butylbromide was administered when the second part of the duodenum had been entered. The Olympus JFB II side-viewing duodenascope was used. A polyethylene cannula filled with Hypaque was introduced into the ampulla of Vater. Contrast medium was then injected under X-ray control. When only the pancreatic duct was outlined, great care was taken to inject a minimum of contrast. However, when the common bile duct was shown, sufficient contrast (20 to 40 ml) was injected to delineate the bile ducts adequately. Radiographs were then taken, initally with the cannula in position, and later with all instruments withdrawn from the patient.

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Case Reports Case 1 (M. G.). A 30-year-old male accountant, with a 14-year history of mild diarrhea, was found to have total colitis and underwent a panproctocolectomy. Histology of the colon

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showed noninvasive carcinoma, and an operative liver biopsy showed granulomas and mild peribiliary inflammation and fibrosis. Two years later he developed jaundice with pale effluent from his ileostomy, dark urine, and pruritus. Examination revealed a slightly enlarged liver. Serum bilirubin was 16.8 mg. dl- 1 , serum alkaline phosphatase 26 King-Armstrong (KA) units dl- 1, and tests for fecal occult blood were positive. The jaundice rapidly became deeper. A percutaneous cholangiogram was unsuccessful, and the biliary duct system was thought to be narrowed or obliterated. A needle biopsy of the liver showed the changes of severe cholestasis. By now the serum bilirubin was 38 mg. dl - 1 • The patient was started on prednisone 30 mg, three times a day, and 3 days later the bilirubin had fallen to 27 mg·dl - 1• The patient was transferred to the Royal Free Hospital and a retrograde cholangiogram was performed (fig. 1). The gallbladder did not fill.

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At laparotomy a cholangiocarcinoma at the level of the insertion of the cystic duct was completely resected. He had an uneventful postoperative course, and by 3 weeks the jaun. dice had disappeared. Case 2 (G. M.). Eight years ago this 35-yearold housewife developed ulcerative colitis and was treated with salazopyrin. Two years ago she developed right upper quadrant pain and a cholecystogram showed a poorly functioning gallbladder. A cholecystectomy was performed. An operative cholangiogram revealed a slightly narrowed biliary tree, but no stones were visible. An operative liver biopsy showed mild periportal inflammation and fibrosis suggestive of pericholangitis. Postoperatively she had per· sistent pain with slightly abnormal liver function tests. The right subphrenic space was explored but found to be clear. Eighteen months ago she developed transient jaundice with dark urine, pale bulky stools, and mild itching. A liver biopsy showed periportal fibrosis, inflammation, and piecemeal necrosis. One year ago she again became slightly jaun· diced. A firm enlarged liver and a few vascular spiders were found. Investigations revealed a WBC of 11,300 mm - 3 with an eosinophilia of 1,695 mm - 3, serum bilirubin 2.4 mg.dl- 1 (con· jugated 2.0 mg. dl - 1 ), serum alkaline phosphatase 172 KA units · dl - \ serum cholesterol 350 mg. dl- \ and antinuclear antibody was positive to a titer of 1:40. On admission to the Royal Free Hospital her serum bilirubin was 18 mg · dl- 1, serum alkaline phosphatase 180 KA units· dl - \ serum aspartate transaminase 88 IU ·liter- 1, and serum cholesterol of 690 mg. dl- 1 ; antinuclear factor was positive to a titer of 1:10. These findings made it imperative to determine whether a surgical cause of the cholestasis existed. A retrograde cholangiogram was therefore performed and revealed a generalized and severe sclerosing cholangitis of the whole biliary tree (fig. 2) . Surgical intervention was not necessary. After the procedure the patient developed fever and tenderness in the right hypochondrium. Blood cultures were negative, but the fever responded to treatment with ampicillin for presumed ascending cholangitis. Case 3 (J. B.). Four years ago this 21-year-old motor mechanic developed ulcerative colitis and was treated with salazopyrin for 2 years with remission of diarrhea. Three months before admission to the Royal Free Hospital he became FIG. 1. Case 1. An extremely irregular stricture jaundiced and tired and had one hematemesis. (marked by an arrow) is demonstrated high in the Examination revealed hepatosplenomegaly. common bile duct (B). This was later shown to be Investigations showed a severe iron deficiency cholangiocarcinoma. P, pancreatic duct. anemia with a hemoglobin of 3 g · dl- 1 . A barium

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FIG. 2. A and B , case 2. The multiple strictures and "beadings" affecting the extrahepatic and intrahepatic biliary tree (B) are characteristic of sclerosing cholangitis. B shows the common bile duct irregularities more clearly. The pancreatic duct (P) is also visualized.

swallow demonstrated esophageal varices and a barium enema a panproctocolitis. A liver biopsy showed periportal fibrosis and cholangitis suggestive of large bile duct disease . In view of the persistent jaundice he was transferred to the Royal Free Hospital. Liver function tests showed serum alkaline phosphatase 82 KA units -dl- 1, serum aspartate transaminase 91 IU -liter- 1, (5- 15) serum cholesterol 270 mg-dl - 1 , serum bilirubin 1.7 mg-dl - 1 (conjugated 1.3 mg . dl - 1 ), serum total protein 8.2 g. dl - 1 , and serum albumin 3.9 g . dl - '. Tests for hepatitis B antigen and a-1-fetoprotein were negative. An endoscopic examination of the upper gastrointestinal tract confirmed the presence of varices, and a retrograde cholangiogram showed the typical changes of sclerosing cholangitis involving the whole of the biliary tree (fig. 3). The colitis is in remission and medical treatment is not indicated at the moment. Case 4 (P. B.). This 16-year-old schoolboy had two episodes of bloody diarrhea and mucus 6 months before his referral to the Royal Free Hospital. A diagnosis of mild colitis was made . Two months prior to his admission he developed nausea and vomiting and a few days later became jaundiced. Investigations at this time were serum bilirubin 2.5 mg -dl- 1 , serum alkaline phosphatase 25 KA units . dl - ', and serum SGPT greater than 125 IU -liter-'. Tests for fecal occult blood were persistently positive. The patient became more unwell and the jaundice deepened, and he was transferred to the Royal Free Hospital.

Examination now showed a deeply jaundiced, ill boy with an enlarged liver. Investigations revealed serum total bilirubin 24 .6 mg -dl - ' (conjugated 24.4 mg . dl - ') , serum alkaline phosphatase 16 KA units . dl - 1, serum aspartate transaminase 364 IU -liter - ', serum cholesterol135 mg -dl - 1, serum total protein 7.8 mg -dl- 1 , and serum albumin 3.7 g-dl- 1 • A test

FIG. 3. Case 3. The lower portion of the common bile duct (B) is narrowed, and intrahepatic duct narrowings and irregularities are also obvious. The pancreatic duct (P) and gallbladder (GB) are also shown.

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for hepatitis B antigen was negative; the smooth muscle antibody test was positive (titer 1:40). Thrombotest was 19%, serum ceruloplasmin was 25 mg. dl - 1, and serum copper 115 J.lg · dl - 1 • The immediate clinical problem was to exclude an extrahepatic cholestasis. The low thrombotest made a liver biopsy hazardous. A retrograde cholangiogram was therefore undertaken and showed a normal biliary tree, excluding extrahepatic obstruction. The patient improved with vitamin K 10 mg intramuscularly and prednisolone 30 mg per day. A liver biopsy performed just prior to discharge showed. the changes of a long-standing, probably vJral, hepatitis.

Discussion When evaluating a new technique such as this, it must first be compared with existing techniques with regard to safety and diagnostic potential. Percutaneous needle liver biopsy provides helpful information in the differential diagnosis of jaundice occurring with ulcerative colitis, 8 but even when features of sclerosing cholangitis and large duct obstruction are seen the nature and extent of the lesion is not apparent. In these cases in particular, transhepatic percutaneous cholangiography is unlikely to succeed (case 1), because of the fibrosis and narrowing of the biliary radicles. 9 In the presence of jaundice, intravenous cholangiography is often unsuccessful, 10 especially if serum bilirubin level exceeds 4.0 mg · dl- 1 . Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure which can yield excellent contrast radiology of the biliary system and which carries very little risk to the patient. 11 However, when evidence of partial obstruction to the biliary tree is encountered, it is important to be aware of the possibility of ensuing ascending cholangitis (case 2). In this situation we now administer antibiotics immediately on completing the procedure, and, to date, this has been effective in preventing this complication. In case 1, a short, extremely irregular stricture high in the common bile duct was delineated in a patient whose liver biopsy had been thought to show primary biliary cirrhosis 4 years previously, and in whom a

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recent attempt at percutaneous transhepatic cholangiography had failed. The normal caliber and outline of the duct below the stricture favored the diagnosis of cholangiocarcinoma rather than of sclerosing cholangitis, although the latter may very rarely be confined to intrahepatic ducts. 12 The shortness of the involved segment and the severity of the obstruction were clear indications for prompt surgery, and carcinoma was successfully resected. By contrast, in case 2, ERCP showed the typical changes of sclerosing cholangitis, namely multiple strictures, with "beading" of ducts between the narrowed segments, and as is usually the case, 13 involvement of both the intrahepatic and extrahepatic systems. In this, and in case 3 where the changes of sclerosing cholangitis were less severe but similarly widespread, surgery was averted. Thompson et a!. 14 reported 9 patients in whom operation was necessary to diagnose the disease, and in whom the biliary tracts were decompressed. Six of these patients died from subsequent biliary cirrhosis, liver failure, or bleeding. These authors contend that a definitive diagnosis of sclerosing cholangitis can only be made by operative cholangiography and histological examination. We, however, agree with others 15 that ERCP will demonstrate the characteristic radiological appearance of the disease, and avert the hazards of laparotomy and exploration of the biliary tree in many cases. Our experienc~ extends to 9 patients, in all of whom ERCP has provided a diagnosis which has not needed revision. Case 4 illustrates the clinical difficulty of excluding a surgical cause for cholestasis in an ill, jaundiced patient. Because of the depth of icterus any attempt at oral or intravenous cholangiography would have been unsuccessful and the clotting disorder precluded either a liver biopsy or percutaneous cholangiography. The normal biliary tree made a medical cause for the cholestasis certain. REFERENCES 1. De Dombal FT, Goldie W, Watts JMcK, et a!:

Hepatic histological

changes in ulcerative

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2.

3.

4.

5.

6.

7.

8.

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colitis-a series of 58 consecutive operative liver biopsies. Scand J Gastroenterol 1:220-227, 1966 Mistilis SP: Pericholangitis and ulcerative colitis. 1. Pathology, etiology and pathogenesis. Ann Intern Med 63:1-16, 1965 Holdsworth CD, Hall EW, Dawson AM, et a!: Ulcerative colitis in chronic liver disease. Q J Med 34:211-222, 1965 Myers RN, Cooper JH, Padis N: Primary sclerosing cholangitis. Complete gross and histologic reversal after long-term steriod therapy. Am J Gastroenterol 53:527- 538, 1970 Thorpe MEC, Scheuer PJ, Sherlock S : Primary sclerosing cholangitis, the biliary tree, and ulcerative colitis. Gut 8:435- 448, 1967 Roberts-Thomson IC, Strickland RG, Mackay IR: Bile duct carcinoma in chronic ulcerative colitis. Aust NZ J Med 3:264-267, 1973 Morowitz DA, Glagov S, Dordal E, et a!: Carcinoma of the biliary tract complicating chronic ulcerative colitis. Cancer 27:356- 361, 1971 Dordal E, Glagov S, Kirsner JB: Hepatic lesions

9.

10. 11.

12.

13.

14. 15.

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in chronic inflammatory bowel disease. Gastroenterology 52:239-253, 1967 Brantigan CO , Brantigan OC: Primary sclerosing cholangitis: case report and review of the literature. Am Surg 39:191-198, 1973 Wise RE: Current concepts of intravenous cholangiography. Radio! Clin North Am 4: 521-524, 1966 Cotton PB: Cannulation of the papilla of Vater by endoscopy and retrograde cholangiopancreatography (ERCP). Gut 13:1014- 1025, 1972 Bhathal PS, Powell LW: Primary intrahepatic obliterating cholangitis: a possible variant of 'sclerosing cholangitis'. Gut 10:886-893, 1969 Rogers JV, Copeland AJ, Schroder JS, et al: Sclerosing cholangitis-roentgenographic features. South Med J 65:587- 594, 1972 Thompson BW, Read RC, White HJ : Sclerosing cholangitis. Arch Surg 104:460-464, 1972 Blumgart LH, Salmon P , Cotton PB, et al: Endoscopy and retrograde choledochopancreatography in the diagnosis of the jaundiced patient. Lancet 2:1269-1276, 1972