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

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?

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?

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.

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

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.

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?

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

ASMR of all parenchymal tumours, HCC, unspecified tumours and intra + extrahepatic CCA in Men, Eng &Wales, 1968 - 1996 Taylor-Robinson et al., Gut 2001

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

Intrahepatic CCA mortality increased 9% in M & F, 1990-2008, 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

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?

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

CCA: Causes (Aetiology) & Known Risk Factors Bergquist et al. 2015 Best Pract Res Clin Gastro

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?

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

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?

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

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

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