1. Cholangiocarcinoma – What is it?
Dr Shahid A Khan
Consultant Liver Specialist St Mary's Hospital
Imperial College London
AMMF Information Day at Imperial College London
10th May 2016
St Mary’s Hospital Campus

2. AMMF Information Day at Imperial College London
Cholangiocarcinoma (CCA)
What is it?
How many people are affected (epidemiology)?
What causes it?
How is it diagnosed?
What are the unmet needs?

3. AMMF Information Day at Imperial College London
Cholangiocarcinoma (CCA)
What is it?
How many people are affected (epidemiology)?
What causes it?
How is it diagnosed?
What are the unmet needs?

4. Cholangiocarcinoma (CCA)
Cancer = a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body
Cholangiocarcinoma (CCA) is a cancer of the bile ducts
Since mid 1990s, more deaths coded in UK due to CC than HCC.
Rise in CC unknown, not explained by improved diagnosis. Apparent increased intrahep CC partly explained by misclassification of Klatskin/ perihilar? But if all diagnostics – why not levelling off (CT/ MR/ ERCP been around for a few yrs), and why not more early stage tumours?
Mean estimated annual percentage change. Corrected for age.

5. CCA: Intrahepatic/ Perihilar/ Extrahepatic
50-60% “Perihilar”: arise at bifurcation of main ducts - pCCA
20-30% distal CBD - eCCA
10-20% arise in intrahepatic ducts of liver - iCCA

6. Cholangiocarcinoma (CCA)
A cancer in a body organ can be primary or secondary
CCA is the second commonest primary liver tumour after Hepatocellular Carcinoma (HCC)
5-10% all primary liver cancers
Peak age 7th decade
Slight male preponderance
Since mid 1990s, more deaths coded in UK due to CC than HCC.
Rise in CC unknown, not explained by improved diagnosis. Apparent increased intrahep CC partly explained by misclassification of Klatskin/ perihilar? But if all diagnostics – why not levelling off (CT/ MR/ ERCP been around for a few yrs), and why not more early stage tumours?
Mean estimated annual percentage change. Corrected for age.

7. AMMF Information Day at Imperial College London
Cholangiocarcinoma (CCA)
What is it?
How many people are affected (epidemiology)?
What causes it?
How is it diagnosed?
What are the unmet needs?

8. Epidemiology of CCA: Worldwide
Incidence varies, reflecting geographical risk factors & genetic differences

9. ASMR of all parenchymal tumours, HCC, unspecified tumours and intra + extrahepatic CCA in Men, Eng &Wales,
Taylor-Robinson et al., Gut 2001

10. Studies from around the world show changing trends in Incidence/Mortality of CCA:
Intrahepatic CCA↑
Extrahepatic CCA↓
CCA Overall↑
Since mid-1990’s, iCCA is commonest recorded cause of death from a primary liver tumour in England & Wales, ahead of HCC
Total deaths risen 30-fold: 36 in 1968 to > 2100 in 2013
Large rise in iCCA Age-standardised Mortality Rates (ASMR):
males 0.1 to 1.5; females 0.05 to 1.25
Largest statistical increase in any tumour over this time period
Total deaths from HCC: 472 in 1968 to approx 1500 in 2014

11. Intrahepatic CCA mortality increased 9% in M & F, , reaching rates of 1.1/100,000 men and 0.75/100,000 women
Highest rates in UK, Germany, and France (1.2–1.5/100,000 men, 0.8–1.1/100,000 women)
Joinpoint analysis for age-standardized (world population) death certification rates from intrahepatic cholangiocarcinoma (ICC) in 12 major selected European countries, the European Union (EU), the United States, Japan, and Australia, 1990–2010. Men, ; women .
Bertuccio P et al. Ann Oncol 2013

12. AMMF Information Day at Imperial College London
Cholangiocarcinoma (CCA)
What is it?
How many people are affected (epidemiology)?
What causes it?
How is it diagnosed?
What are the unmet needs?

13. CCA: Causes (Aetiology) & Known Risk Factors
Primary sclerosing cholangitis
Parasitic Infection (Opisthorcis viverrini, Clonorchis sinensis)
Fibropolycystic Liver Disease
Intrahepatic Biliary Stones
Chemical Carcinogen Exposure
Chronic Liver Disease
Viral Hepatitis
Obesity
Type 2 Diabetes
>70% of CCA cases in West have NO known risk factors

14. CCA: Causes (Aetiology) & Known Risk Factors
Bergquist et al Best Pract Res Clin Gastro

15. AMMF Information Day at Imperial College London
Cholangiocarcinoma (CCA)
What is it?
How many people are affected (epidemiology)?
What causes it?
How is it diagnosed?
What are the unmet needs?

16. Hence most CCA cases are diagnosed very late
CCA: How is diagnosed?
Symptoms not specific and occur late in the disease process
Discomfort, weight loss, jaundice, itching, sometimes dark urine, pale stool
Imaging
Ultrasound, CT, MRI scans
but the appearances are non-specific
Biopsies (various routes)
Can be difficult due to location
Tumour markers in blood
None are very accurate
Hence most CCA cases are diagnosed very late

17. AMMF Information Day at Imperial College London
Cholangiocarcinoma (CCA)
What is it?
How many people are affected (epidemiology)?
What causes it?
How is it diagnosed?
What are the unmet needs?

18. Unmet Needs and Future (hope) in CCA
Greater awareness of this disease
We need more accurate early diagnostic tools to enable more patients having curative surgery
Need for better 2nd line treatments
Ongoing trials in advanced CCA – chemo; local techniques e.g. ablation
Future hope: CCA treatment will be more individualized, when the genetic profile of a tumor can predict sensitivity or resistance to an agent 18

19. Acknowledgments NIHR Biomedical Research Centre
Biomedical Research Council (BMRC)
Imperial College Healthcare Trustees
(donations from Mr. and Mrs. Barry Winter)

20. Cholangiocarcinoma – What is it?
Dr Shahid A Khan
Consultant Liver Specialist St Mary's Hospital
Imperial College London
AMMF Information Day at Imperial College London
10th May 2016
St Mary’s Hospital Campus