Ulcerative Colitis Associated with Cholangiocellular Carcinoma: A Case Report and Literature Review

Abstract

To investigate the possibility for Ulcerative Colitis (UC) to progress to cholangiocellular carcinoma (CCC), clinical data of a UC patient with concomitant CCC were analyzed and the relevant literature was reviewed. The patient was diagnosed with UC 14 years prior and had been treated with sulfasalazine. Her UC symptoms were alleviated after administration of sulfasalazine, but liver function was repeatedly found to be abnormal. She was diagnosed with CCC by ultrasound and magnetic resonance imaging. A review of the literature suggests that UC is easily associated with concomitant primary sclerosing cholangitis, which progresses to CCC in 11% of cases. Clinicians should be aware that UC may progress into CCC. UC patients with repeated abnormal liver function, especially those who have serum alkaline phosphatase elevation, should undergo relevant examinations to clarify the diagnosis.

Keywords: Ulcerative colitis; Primary sclerosing cholangitis; Cholangiocellular carcinoma

Introduction

Primary Sclerosing Cholangitis (PSC) is the most common hepatobiliary complication of Ulcerative Colitis (UC). The majority of PSC cases ultimately progress to end-stage liver disease, and ~11% are associated with concomitant Cholangiocellular Carcinoma (CCC). This study provides a clinical analysis of a UC patient with concomitant CCC and reviews the relevant literature to raise awareness of the possibility of progression of UC to CCC.

Clinical Data

General data

The patient was a 24-year-old woman who was admitted to our hospital because of repeated abnormal liver function over a period of 14 years and upper abdominal pain for >1 month. She started taking mesalazine after she was diagnosed with UC in 1999. Several follow-up examinations of liver function found elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT). In particular, ALP and GGT were elevated to 2–3-fold of the Upper Limit of Normal (ULN). During follow-up, the patient had no discomfort such as bloating or abdominal pain; no nausea, vomiting or anorexia; and no fever, rash or xanthochromia of the skin and sclera. No attention was paid and no further diagnosis or treatment was received. In 2009, her UC was well controlled and the dose of mesalamine was therefore gradually reduced to withdrawal. Six months after withdrawal of mesalamine, liver function tests showed elevated liver enzymes, mainly ALP and GGT that were 1–2- fold of ULN. The patient visited the hospital but liver biopsy showed no obvious abnormalities. She was given intermittent, symptomatic treatment of the liver. In February 2015, she had upper abdominal pain after meals, with no obvious predisposing causes. The patient denied acid reflux, belching, nausea, vomiting, diarrhea, fever, rash, jaundice, joint pain and other discomforts. She visited a local hospital and liver function tests showed: total bilirubin 21 μmol/L, conjugated bilirubin 14 μmol/L, albumin 42 g/L, ALT 117 IU/L, AST 131 IU/L, and ALP 962 IU/L, and she was negative for hepatitis A, B, C and E virus markers. Gastroscopy showed superficial gastritis, polypoid bulge, and erosion in the gastric antrum, and cardiac polyp (probably inflammatory). Gastric antral mucosal biopsy showed severe active chronic superficial inflammation in the mucosa with erosion. Abdominal ultrasound showed hepatomegaly, diffuse liver lesion, and hypoechoic mass in the left hepatic lobe, and gallbladder wall edema. Abdominal contrast-enhanced CT showed focal liver lesions, suspicious for neoplastic lesions, probably atypical hemangioma or bile-duct-derived tumors. To clarify the nature of focal liver lesions, the patient was admitted to the Department of Gastroenterology in our hospital. Since disease onset, she remained in a clear state of consciousness with good mental health, good appetite, sufficient sleep, normal urination and defecation, and no significant weight change. She had a 14-year history of UC and took mesalazine previously. Six years prior to admission, use of mesalazine was gradually reduced to withdrawal because of good disease control, and she was still in remission. She underwent an appendectomy at Beijing Children’s Hospital in 1999, with a history of allergy to cephalosporins. She denied a history of hepatitis, smoking, alcohol drinking, or toxicant exposure. She was unmarried and had not given birth, and had a normal menstrual cycle.

Physical examination

The patient had a body temperature of 36.8°C, pulse rate of 78 beats/min, respiratory rate of 18 beats/min, and blood pressure of 110/78 mmHg. She was clearly conscious, mentally normal, physically active, and cooperative upon examination. Her skin and sclera showed xanthochromia and there were no hemorrhagic spots, liver palms, or spider angioma on the skin. She had no enlargement of systemic superficial lymph nodes. Her percussion and breath sounds of both lungs were clear. She had no precordial bulge, and the border of cardiac dullness was within normal limits (heart rate 78 beats/ min). Her heart rhythm was regular and no pathological murmurs were auscultated in auscultatory valve areas. Her abdomen was flat with a 5-cm score in the center of the abdomen. No subcutaneous varicose veins were observed in the abdominal wall. She had a soft abdomen, with right upper quadrant tenderness but no rebound tenderness, muscle tension or mass. Her liver was palpable with one finger under the costal margins, while the spleen was not palpable. Her renal and hepatic regions were not sensitive to percussion. Shifting dullness was negative. Bowel sound frequency was 3 times/ min. Neurological examination produced negative results. No pitting edema was observed in either lower extremity.

Laboratory tests

Blood: erythrocyte count 3.60 × 1012/L, hemoglobin 104 g/L, platelet count 501 × 109/L, leukocyte count 9.67 × 109/L, percentage of neutrophils 71.3%, percentage of lymphocytes 16.2%; erythrocyte sedimentation rate: >120 mm/H. Urine: bilirubin ++, without any other abnormalities; stool: normal; fecal occult blood: negative. Liver function: total bilirubin 64.4 μmol/L, direct bilirubin 59.7 μmol/L, albumin 33 g/L, globulin 38 g/L, ALT 55 U/L, AST 61 U/L, ALP 561 U/L, GGT 382 U/L, lactate dehydrogenase 201 U/L, cholinesterase 4132 U/L, prealbumin 0.12 g/L; kidney function: urea 1.8 mmol/L, creatinine 39 μmol/L, uric acid 139 μmol/L. Coagulation: prothrombin time 12.2 s, international normalized ratio 1.05, activated partial thromboplastin time 36.5 s, D-dimer 2.17 mg/L. Tumor markers: carbohydrate antigen (CA)125 451.3 IU/mL; a fetoprotein, carcinoembryonic antigen, CA199 within the normal range. Ferritin >2 μg/mL electrolyte and autoantibodies within the normal range.

Auxiliary examination

Upper abdominal contrast-enhanced magnetic resonance imaging (Figure 1) revealed space-occupying lesions in the left hepatic lobe, with a tubercle in the caudal lobe involving blood vessels in the left lobe, suspicious for atypical hemangioma or bile duct Malignant Tumor (MT); other features included mild porta hepatis lymphadenopathy, and edema and thickening of the gallbladder. Contrast-enhanced ultrasound for liver imaging showed multiple solid lesions in the left lobe, highly suspicious for MT (cholangiocytederived); embolization in the left portal vein; and porta hepatis lymphadenopathy. Computed Tomographic Angiography (CTA) of the hepatic artery and computed tomography venography (CTV) of the portal vein, hepatic vein and inferior vena cava revealed invasion of the left hepatic artery, left and middle hepatic veins, and left portal vein. Nuclear medicine imaging of systemic cancer by Positron Emission Tomography (PET)/CT indicated that the patient was highly suspicious for MT in the left lobe with intrahepatic metastasis, and porta hepatis, retroperitoneal and thoracic lymph node metastases, as well as abdominal and pelvic implantation metastases, with a small amount of peritoneal fluid.

    

    

    Figure 1:  Large liver lesion in the left hepatic lobe with unclear boundary, approximately 7.1×5.1 cm; heterogeneous high signal on T2-weighted imaging (A) and
high signal on diffusion-weighted imaging (B); MRCP revealed irregular intrahepatic bile duct stricture (C); contrast-enhanced arterial phase lesions presented with
peripheral irregular enhancement (D); CTA of the hepatic artery and CTV of the portal vein, hepatic vein and hepatic artery indicated invasion of the left hepatic
artery, left and middle hepatic veins, and left hepatic portal vein, with less clear boundaries (E,F).