13 liver cancer

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13 liver cancer

  1. 1. Department of Hepatobiliary Oncology,SYSUCC Anti-liver cancer team Shengping Li, M.D., Ph.D
  2. 2. <ul><li>Advanced stage </li></ul><ul><li>Low resection rate </li></ul><ul><li>High recurrence </li></ul><ul><li>Decompensation liver function </li></ul>Poor prognosis Fierce “癌王” “lion king”
  3. 3. Liver cancer PLC (Primary Liver Cacner) Secondary Liver Cancer HCC(Hepatocellular carcinoma) CCC(Cholangiocellular carcinoma) HCC and CCC mixed HCC
  4. 4. Epidemiology “ Hot spots” – 150 per 100 000 US, Australia : 2 per 100 000 <ul><li>The fifth most common </li></ul><ul><li>cancer worldwide </li></ul><ul><li>CA Cancer J Clin 2005 </li></ul>
  5. 5. <ul><li>High incidence In China </li></ul><ul><li>Shanghai </li></ul><ul><li>Jiangsu </li></ul><ul><li>Fujiang </li></ul><ul><li>Guangdong </li></ul><ul><li>Guangxi </li></ul>Epidemiology
  6. 6. Trend of Death rate of malignant tumor in China Lung Liver Stomach 128 2004-2005 Stomach Liver Lung 106 1990-1992 Stomach Esophagus Liver 80 1973-1974 Three leading causes of Ca. death Death Rate (per100,000) Period(years)
  7. 7. Etiology <ul><li>Hepatitis </li></ul><ul><li>Alcoholism </li></ul><ul><li>Environmental factors </li></ul><ul><li>molecular and Cytogenetic alterations </li></ul>
  8. 8. HBV 80% (Asia and Africa), 100 million china HCV 70% (Japan,West countries) Hepatitis virus infection
  9. 9. Alcoholism: alcoholic cirrhosis
  10. 10. Food contaminated with aflatoxin Decayed peanut,corn Turkey Liver cancer
  11. 11. Liver Flukes (Clonorchis sinensis )
  12. 12. Liver Flukes Infestation
  13. 13. Mutation of oncogene and tumor suppressor gene (癌基因和抑癌基因的突变) N-ras,c-myc,cfms,CSF-1R, IGF-II , p53 , TTR, DLC-1, LPTS, WFDC1, HCCS1, HCRP1, 17HSDB2 Chromosomal alterations ( 染色体改变) Gain (获得) :1q,8q and 20q Lose (缺失) : 4q,8p,13q,16q, and 17p ( Li SP, et al . J Hepatology 2001) Molecular and cytogenetic aberration (分子和细胞遗传学变异)
  14. 14. <ul><li>Peoples lived in high incidence of liver cancer area </li></ul><ul><li>Peoples persistent infection of hepatitis virus </li></ul><ul><li>Family history of liver cancer </li></ul><ul><li>Liver cancer history previously </li></ul>High Risk Group
  15. 15. <ul><li>Early stage </li></ul><ul><li>Subclinical stage </li></ul><ul><li>Non symptom and sign </li></ul>Clinical manifestation
  16. 16. <ul><ul><li>Abdominal pain and distention </li></ul></ul><ul><ul><li>Weight loss </li></ul></ul><ul><ul><li>Hepatomegaly : 80% </li></ul></ul><ul><ul><li>Abdominal mass </li></ul></ul><ul><ul><li>Jaundice ,ascites </li></ul></ul>Clinical stage
  17. 17. Diagnosis of HCC <ul><li>Serological (tumor markers) </li></ul><ul><li>Radiological </li></ul><ul><li>Cytological </li></ul><ul><li>Histological </li></ul><ul><li>Either alone or in combination </li></ul>
  18. 18. Tumor markers for HCC Most common used
  19. 19. Diagnostic Imaging for HCC
  20. 20. Radiology--US <ul><li>Ultrasound </li></ul><ul><ul><li>Availability, cost </li></ul></ul><ul><ul><li>Operator dependant </li></ul></ul><ul><ul><li>Therapeutic role. </li></ul></ul>
  21. 21. Radiology--CT <ul><li>Triphasic CT </li></ul><ul><ul><li>detect 30 – 40% more tumour nodules than conventional CT. </li></ul></ul><ul><li>Lipiodol </li></ul><ul><ul><li>Retained by all hypervascular liver tumours. </li></ul></ul>
  22. 22. Radiology--MRI <ul><li>Slightly higher sensitivity than CT in detecting hepatic lesions. </li></ul><ul><li>Cost, availability. </li></ul>
  23. 23. <ul><li>Diagnosis and treatment simultaneously </li></ul><ul><li>Invasive, not routinely used </li></ul>Radiology--angiograph
  24. 24. <ul><ul><li>Expensive </li></ul></ul><ul><ul><li>Whole body scaning </li></ul></ul><ul><ul><li>Tumor cell Function </li></ul></ul>Radiology-- Positron Emission computed Tomography, PET/CT
  25. 25. Liver Biopsy <ul><li>Biopsy now rarely required to diagnose HCC. </li></ul><ul><li>Avoid biopsy of potentially resectable tumour. </li></ul><ul><ul><li>Risk of needle track seeding 1 – 3% </li></ul></ul><ul><ul><li>Risk of bleeding </li></ul></ul>
  26. 26. <ul><li>US and CT most commonly used clinically </li></ul>Diagnostic imaging for HCC
  27. 27. <ul><li>AFP≥400 n g/L, palpable mass or space-occupying lesions in the liver by imaging </li></ul><ul><li>2. AFP<400 n g/ L, specific liver cancer images confirmed by at least two kinds of imaging scanning </li></ul><ul><li>3. Clinical manifestation of liver cancer with pathological diagnosed extrahepatic liver cancer and metastases liver tumor ruled out </li></ul>Standard rule for Diagnosis of HCC
  28. 28. Clinical Application of AFP <ul><ul><li>1.Screening of liver cancer </li></ul></ul><ul><ul><li>2.Dianosis of liver cancer </li></ul></ul><ul><ul><li>3.Predicting prognosis after treatment </li></ul></ul><ul><ul><li>4.Surveillance of recurrence after treatment( decrease to normal level within 1-2 months after resection) </li></ul></ul>
  29. 29. Differential diagnosis <ul><li>AFP positive </li></ul><ul><li>chronic active hepatitis, cirrhosis, testicular tumor, pregnancy </li></ul><ul><li>AFP negative </li></ul><ul><li>haemangioma, metastatic liver carcinoma, abscess, focal nodular hyperplasia (FNH), hepatic hydatidosis </li></ul>
  30. 30. Pregnancy with HCC Delivery baby and resection of HCC simultaneously
  31. 31. Hepatic haemangioma
  32. 32. Colon cancer liver metastasis
  33. 33. Focal Nodular Hyperplasia (FNH)
  34. 34. Hepatic Abscess
  35. 35. Hepatic Hydatidosis
  36. 37. Therapeutic Option for HCC
  37. 38. Surgery <ul><li>Langenbuch 1888 </li></ul><ul><ul><li>first left hepatic lobectomy </li></ul></ul><ul><li>Tiffany 1890 </li></ul><ul><ul><li>first liver resection for solid tumour </li></ul></ul><ul><li>Starzl 1963 </li></ul><ul><li>first liver graft </li></ul>
  38. 39. Principles of Surgical Management <ul><li>Determining resectability </li></ul><ul><ul><li> Stage of tumour </li></ul></ul><ul><ul><li> Functional hepatic reserve </li></ul></ul><ul><li>80%-90% of HCC occur in cirrhotic livers </li></ul><ul><li>Less than 20% of patients with HCC are candidates for resection at time of presentation. </li></ul>
  39. 40. 1. Staging <ul><li>TNM </li></ul><ul><ul><li>Stage III, IV unresectable </li></ul></ul><ul><li>Okuda </li></ul><ul><li>CLIP (Cancer of the Liver Italian Program) </li></ul><ul><li>Barcelona Staging Classification </li></ul><ul><ul><li>Performance scores, Okuda, tumour morphology </li></ul></ul><ul><li>French Staging Classification </li></ul><ul><ul><li>Performance scores, LFT, US </li></ul></ul>
  40. 41. TNM Staging System
  41. 42. staging <ul><li>Because the combined impact of liver disease </li></ul><ul><li>and tumor burden is not yet fully understood, and </li></ul><ul><li>the cause of HCC may vary geographically, none </li></ul><ul><li>of the currently used staging systems fulfils all the </li></ul><ul><li>requirements for stratification of patients with HCC </li></ul><ul><li>into groups of different prognosis and therapeutic </li></ul><ul><li>recommendations. None of the staging systems is </li></ul><ul><li>universally accepted. </li></ul>
  42. 43. 2. Functional Reserve <ul><li>Resection only of benefit in patients with adequate functional reserve. </li></ul><ul><li>Assessment of liver function : </li></ul><ul><ul><li>Synthetic capacity of liver </li></ul></ul><ul><ul><ul><li>Serum albumin, prothormbin time </li></ul></ul></ul><ul><ul><li>Excretion of metabolites </li></ul></ul><ul><ul><ul><li>Indocyanine dye test, bilirubin, bile acid profile </li></ul></ul></ul><ul><ul><li>Child-Pugh Classification </li></ul></ul>
  43. 44. Child Pugh Classification
  44. 45. 2. Functional Reserve <ul><li>Portal hypertension </li></ul><ul><li>Estimation of likely remaining liver volume after resection </li></ul><ul><li>Comorbidities </li></ul><ul><ul><li>ASA / Performance scores </li></ul></ul><ul><ul><li>Nutritional state : Perioperative nutritional support decreases post operative morbidity </li></ul></ul>
  45. 46. 5-year survival 26-50%, mean 30% 5 years recurrence rate is about 70% A critical clinical problem Hepatectomy
  46. 47. 6 m Pre-op
  47. 48. Cutting edge recurrence
  48. 49. Liver transplantation <ul><li>Potentially resect HCC while replacing the cirrhotic liver </li></ul><ul><li>Milan criteria for HCC </li></ul><ul><li>Single lesion <5cm or upto three lesions <3cm </li></ul>
  49. 50. Limitation <ul><li>Immunosuppression </li></ul><ul><ul><li>Recurrent hepatitis </li></ul></ul><ul><ul><li>Recurrent HCC </li></ul></ul><ul><li>Shortage of donors </li></ul><ul><ul><li>Consider “bridging therapy” to prevent tumour progression. </li></ul></ul><ul><ul><li>Living donors </li></ul></ul>
  50. 51. Non Surgical Management <ul><li>Transcatheter Arterial Chemoembolization </li></ul><ul><li>Percutaneous microwave coagulation therapy </li></ul><ul><li>Percutaneous ethanol injection </li></ul><ul><li>Radiofrequency Ablation </li></ul><ul><li>Cryosurgery </li></ul><ul><li>Systemic Chemotherapy </li></ul><ul><li>Hormonal therapy </li></ul><ul><li>Immunotherapy </li></ul><ul><li>Gene Therapy </li></ul><ul><li>Chinese medicine </li></ul>
  51. 52. Percutanous intervention PEI: percutanous ethanol injection RF: Radiofrequency ablation MCT: microwave coagulation thermotherapy LT: Laser thermotherapy Cryoablation Best option for small unresectable HCC
  52. 53.      将 10 枚象“弹头”一样的小电极通过穿刺针管送入癌组织,多枚小电极从不同的角度和方向“锁定”癌症组织区域,由计算机测算出射频治疗所需的最佳温度,时间,功率和阻抗,由小电极发出高能射频波,在 100—120℃ 的高温下,使癌组织蛋白发生凝固性坏死,达到杀灭癌组织的效果。 3.5cm/15G 10 electrodes Lee Veen needle
  53. 54. Radiafrequency ablation,RF <ul><li>Alternative to PEI </li></ul><ul><li>Applied percutaneously,laparoscopically, during laparotomy </li></ul><ul><li>Expensive but offer a better local control </li></ul><ul><li>Ablation of tumor large than 5 cm in diameter </li></ul>
  54. 56. <ul><li>The most widely used treatments for HCCs which </li></ul><ul><li>are unresectable or cannot be effectively treated with </li></ul><ul><li>percutaneous interventions. </li></ul><ul><li>Embolization agents: Lipiodol,gelfoam </li></ul><ul><li>Chemotherapeutics: doxorubicin, 5-Fu, mitomycin, cisplatin </li></ul><ul><li>Partial responses in 15-55% of patients </li></ul><ul><li>Delays tumor progression and vascular invasion </li></ul><ul><li>Prolongs the survival time compared to conservative management. </li></ul>TACE or TAE
  55. 57. TACE or TAE <ul><li>Patients liver function Child A </li></ul><ul><li>Without vascular invasion or extrahepatic spread. </li></ul><ul><li>Advanced liver disease (Child B or C), treatment-induced liver failure may offset the antitumor effect or survival benefit of the intervention. </li></ul><ul><li>Postoperative adjuvant TACE may improve survival in patients with risk factors for residual tumor </li></ul>
  56. 58. Tumor shrinkage post-TACE
  57. 59. Principles of management <ul><ul><li>Treatment in early stage </li></ul></ul><ul><ul><li>Combination therapy </li></ul></ul><ul><ul><li>Actively( time and again) </li></ul></ul>
  58. 60. Metastasis of HCC <ul><li>Intrahepatic ---port vein pathway, satellite </li></ul><ul><li>Extrahepatic: lung </li></ul><ul><li>Lymphatic pathway: CCC </li></ul><ul><li>Invasion periheaptic organs directly </li></ul><ul><li>Abdominal implantation: tumor rupture </li></ul>
  59. 61. HCC metastasis
  60. 62. Continuing challenges <ul><li>Prevalance of chronic hepatitis </li></ul><ul><li>Low resection rate </li></ul><ul><li>High recurrence rate post-resection </li></ul><ul><li>Shortage of liver donor </li></ul><ul><li>Optimal combination therapy </li></ul><ul><li>Molecular staging system </li></ul>
  61. 63. Thank you!

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