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Cholangiocarcinoma – An Overview Dr Shahid A Khan

Cholangiocarcinoma – An Overview Dr Shahid A Khan Consultant Liver Specialist St Mary's & Hammersmith Hospitals Imperial College London. AMMF Conference/Information Day 11 th May 2017. Cholangiocarcinoma (CCA) What is it? How many people are affected (epidemiology)? What causes it?

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Cholangiocarcinoma – An Overview Dr Shahid A Khan

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  1. Cholangiocarcinoma – An Overview Dr Shahid A Khan Consultant Liver SpecialistSt Mary's & Hammersmith Hospitals Imperial College London AMMF Conference/Information Day 11th May 2017

  2. Cholangiocarcinoma (CCA) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • What are the unmet needs?

  3. Cholangiocarcinoma (CCA) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • 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

  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) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • What are the unmet needs?

  7. 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 7thdecade • Slight male preponderance

  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, 1968 - 1996 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 • Totaldeaths 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 2000 in 2014

  11. 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) Bertuccio P et al. Ann Oncol 2013

  12. Trends in age-adjusted male rates for HCC and iCCA, 1978–2007 Petrick et al. Int J Ca 2016

  13. Male liver cancer incidence rates per 100,000 person-years by year of birth for (a) HCC (b) iCCA (selected countries) Petrick et al. Int J Ca 2016 • 13

  14. Trends in HCC and iCCA rates are similar • But: • Thailand, France, Italy: iCCA increased while HCC decreased • HCC and ICC may have some common risk factors, but geographic areas of increasing ICC rates do not entirely correspond with those of increasing HCC rates • Likely other potential differences in liver cancer aetiology • 14

  15. Average total hospital charges per hospitalization due to CCA (USA) Wadhwa et al. Gastroenterol. Rep. 2016

  16. USA: Sex & race/ethnicity disparities in CCA incidence: 2000–2011 SEER Increasing age associated with increasing incidence of CCA Highest incidence of CCA among men and among Asians Mosadeghi et al., Hep Res 2016

  17. Taiwan: iCCA incidence increased 3-fold: 0.72 to 2.19 eCCA incidence increased 1.5-fold: 0.48 to 0.73 Rising incidence of CCA seen across all ages/genders, esp in > 65 years

  18. Cholangiocarcinoma (CCA) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • What are the unmet needs?

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

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

  21. Cholangiocarcinoma (CCA) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • What are the unmet needs?

  22. 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

  23. Cholangiocarcinoma (CCA) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • What are the unmet needs?

  24. International Liver Cancer Association CCA Guidelines on, 2014

  25. Surgical Resection for CC • Mainstay of treatment, only chance for cure • Goal: R0 resection with adequate remnant liver volume • Perioperative mortality < 5% in specialized centres • OUTCOMES: • Recurrence rates 50 - 60% • Median disease free survival 26 months • 5-year survival 15 – 40%

  26. Molecular Targeted Therapy for CCA – studies so far Sadeghi & Finn, Clin Liv Dis 2014 • Currently no targeted therapy validated for CCA • Little or no improvement in survival • MEK inhib trials included some pts who progressed on 1st line 26

  27. Other Options for Targeted Therapy in Advanced CCA Rizvi et al, Sem Liver Dis 2014 Biomarker adaptive design in future CCA clinical trials? 27

  28. Cholangiocarcinoma (CCA) • What is it? • How many people are affected (epidemiology)? • What causes it? • How is it diagnosed? • What are the treatments? • What are the unmet needs?

  29. Unmet Needs and Future (hope) in CCA • Greater awareness and research funding • More accurate, early diagnostic tools to enable more patients to have potentially curative surgery • Equitable and rapid access for specialist centre opinion • Need for better second and third-line treatments • Ongoing trials in advanced CCA – chemotherapy; local techniques e.g. ablation • Oncological treatment for CCA will be more individualized, when the genetic profile of a tumour can predict response to any given agent • 29

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

  31. Cholangiocarcinoma – An Overview Dr Shahid A Khan Consultant Liver SpecialistSt Mary's Hospital Imperial College London AMMF Conference/Information Day 11th May 2017

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