update on hepatocellular carcinoma€¦ · internal medicine grand rounds july 9th, 2013 steve...
TRANSCRIPT
![Page 1: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/1.jpg)
Update on Hepatocellular Carcinoma
Internal Medicine Grand RoundsJuly 9th, 2013
Steve Scaglione, M.D.
![Page 2: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/2.jpg)
• Epidemiology
• Pathogenesis
• Surveillance
• Diagnosis
• Staging
• Treatment based on Staging
![Page 3: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/3.jpg)
Epidemiology of Hepatocellular Carcinoma
![Page 4: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/4.jpg)
Primary Liver Cancer:The Global Perspective
Total: 748,300 new cases/year diagnosed and 695,900 deaths/year (2008)
Men: • Fifth most frequently diagnosed cancer (523,000 cases; 7.9% of all cancers)
• Second leading cause of cancer deaths
Women:• Seventh most frequently diagnosed Cancer (226,000 cases/year; 6.5% of all cancers)
• Sixth leading cause of cancer deaths
• Jemal eta al. Global Patterns of Cancer Incidence and Mortality Rates and Trends. Cancer Epidemiol Biomarkers Prev;19(8); 1893‐1907
• El‐Serag, H. Epidemiology of Viral Hepatitis and HCC. Gastroenterology. 2012. 142: 1264‐1273
![Page 5: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/5.jpg)
![Page 6: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/6.jpg)
Globocon. Website. Data from 2008
![Page 7: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/7.jpg)
Globocon. Website. Data from 2008
![Page 8: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/8.jpg)
Global Prevalence of HBV and HCV
• El‐Serag, H. Epidemiology of Viral Hepatitis and HCC. Gastroenterology. 2012. 142: 1264‐1273
![Page 9: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/9.jpg)
HBV/HCV and Attributable Fraction of HCC
Ref:Parkin, DM. Global Health Burden of Infectious‐associatedCancers Worldwide in the year 2002. Int J. Cancer. 118. 3030‐3044. 2006
![Page 10: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/10.jpg)
Alcohol, Viral Hepatitis and HCC
• El‐Serag, H. Epidemiology of Viral Hepatitis and HCC. Gastroenterology. 2012. 142: 1264‐1273• Donato F. Alcohol and HCC: The effect of lifetime intake and hepatitis virus infection in Men and
Women. American Journal of Epidemiology. 2002.
![Page 11: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/11.jpg)
Gender Disparity of HCC
• Consistent across risk factors
• Androgen or androgen w/HBV
• Androgen receptor• Expression• Gene polymorphism
• Estrogen/Progesterone
• Fat distribution
• El‐Serag, H. Epidemiology of Viral Hepatitis and HCC. Gastroenterology. 2012. 142: 1264‐1273
![Page 12: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/12.jpg)
Aflatoxin B1 and HCC
• Aflatoxin B1– Mycotoxin produced by Aspergillus– Grows on foods (ie corn/peanuts) stored in warm, damp conditions
– Once ingested AFB1‐exo‐8,9‐epoxide• Binds/damages DNAtumor suppressor p53• 30‐60% of cases of HCC found in endemic areas
– International Agency for Research on Cancer• Carcinogen
– Effect is modified by Chronic HBV infection
• El‐Serag, H. Epidemiology of Viral Hepatitis and HCC. Gastroenterology. 2012. 142: 1264‐1273• Qian GS. Follow‐up study of urinary markers of aflatoxin exposure and liver cancer in China. CEBP
1994; 3:3‐10
![Page 13: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/13.jpg)
Epidemiology of HCC in the USA
EL‐Serag, H. Hepatocellular Carcinoma. NEJM. 2010
• 20,000 cases/year• Past 35yrs, IR has tripled• Fastest growing Cancer in the US• 5 year survival ‐ 12%
![Page 14: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/14.jpg)
Risk Factors for HCC• All causes of Cirrhosis – Annual Incidence 3‐5%
– Alcoholic liver disease– Hepatitis C– Non Alcoholic Fatty Liver Disease (NAFLD)– Inherited metabolic liver disease
• Hemochromatosis• Alpha 1 antitrypsin deficiency• Glycogen storage disease• Autoimmune hepatitis
• Hepatitis B – Cirrhosis ‐ Annual Incidence 3‐5%– Non Cirrhotic – Annual Incidence 0.2%
![Page 15: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/15.jpg)
Hepatocellular Carcinoma in the USA
![Page 16: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/16.jpg)
Projected HCV Incidence & Prevalence
![Page 17: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/17.jpg)
Hepatitis C and risk of Cirrhosis
Chronic Hepatitis C
HCV Infection
Cirrhosis
HCC
25yrs
![Page 18: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/18.jpg)
Risk Factors for HCC in CHC
• Older Age• Duration of HCV infection• Males• Alcohol• Obesity and Diabetes• Co‐infection w/HBV and HIV• Absence of Antiviral treatment• Viral genotype 1b?
![Page 19: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/19.jpg)
Mortality Rate/100,000 age‐adjusted
5.24 to 6.12 (6)4.49 to 5.24 (5)4.28 to 4.49 (5)4.09 to 4.28 (5)3.94 to 4.09 (5)3.75 to 3.94 (6)3.50 to 3.75 (5)3.19 to 3.50 (5)2.74 to 3.19 (5)2.21 to 2.74 (4)Sparse Data (0)
5.24 to 6.12 (6)4.49 to 5.24 (5)4.28 to 4.49 (5)4.09 to 4.28 (5)3.94 to 4.09 (5)3.75 to 3.94 (6)3.50 to 3.75 (5)3.19 to 3.50 (5)2.74 to 3.19 (5)2.21 to 2.74 (4)Sparse Data (0)
Regional Variations in Mortality
![Page 20: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/20.jpg)
Diabetes and risk of HCC
EL‐Serag. Clinical Gastro. 2005
![Page 21: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/21.jpg)
DM and Risk of HCC
El‐Serag. Gastroenterology. 2004
![Page 22: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/22.jpg)
Obesity, Mortality and HCC
![Page 23: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/23.jpg)
NAFLD/NASH & Risk of HCC
• Systematic Review 1991‐2011– 17 Cohort Studies
• 3 population based, 9 clinic based, 5 natural history
– 18 Case control and cross sectional
– 26 Case series
• NAFLD/NASH without cirrhosis – 0‐3% over 20 years
• NASH with Cirrhosis had a higher risk– 2.4% (7yrs) ‐12.8% (3yrs)– Substantially lower risk versus cohorts with HCV Cirrhosis
White D, Kanwal F. Clinical Gastro & Hep 2012
![Page 24: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/24.jpg)
NAFLD & Risk of HCC
Rahman, R. Abstract #97 AASLD 2012
![Page 25: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/25.jpg)
Coffee and HCC
• An inverse relationship between coffee consumption and HCC exists
• Meta‐Analysis through 2007– 6 case‐control studies, 4 cohort studies comprising 2260 cases of HCC
– All showed inverse relationships• 6 studies the the association was statistically significant.
• Summary relative risk 0.54 case control & 0.64 for cohort studies
![Page 26: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/26.jpg)
Pathogenesis of HCC
![Page 27: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/27.jpg)
Hallmarks of Cancers
![Page 28: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/28.jpg)
Molecular Pathogenesis of HCC
![Page 29: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/29.jpg)
Author Year #/type of Patients
# of Mutations
FrequentlyMutated Genes
Strengthsof study
Totoki 2011 1; Japanese 63 TP53, AXIN1
1st HCC genome sequenced
Tao 2011 1;Taiwanese 201 TP53 1st differentstages HCC
Li 2011 10; USA/EU/Asia
429 CTNNB1TP53
Large validation cohort
Guichard 2012 24; French 994 CTNNB1TP53, AXIN1
New B‐catenin pathway
Fujimoto 2012 27; Japanese
147 TP53CTNNB1
1st Large scale WGS
Sung 2012 88; Chinese 344 TERT1
Huang 2012 10; Chinese 347 TP53 Advanced HCC
![Page 30: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/30.jpg)
G1:Good Prognosis:HNRPD, PAQR3, PHF17; DCKChromosome 4p
G2:Bad Prognosis: SORBS3,DLC1,CCDC25;ELP3, PROSC; Chromosome 8p
![Page 31: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/31.jpg)
![Page 32: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/32.jpg)
Prevention of HCC
![Page 33: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/33.jpg)
Prevention of HCC
• HBV vaccination– Safe and effective
– Should be given to all newborns and high‐risk individuals
– Incidence in Taiwan has decreased HCC 65‐75%
![Page 34: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/34.jpg)
Prevention of HCC:Treating HBV
![Page 35: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/35.jpg)
Preventing HCCTreating HBV
![Page 36: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/36.jpg)
Surveillance for HCC
![Page 37: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/37.jpg)
Rationale for Surveillance
![Page 38: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/38.jpg)
Surveillance of HCC:Whom to Screen
![Page 39: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/39.jpg)
Surveillance for HCCHow to Screen
• 2005: Ultrasound and Alpha‐Fetoprotein every 6months
• 2011: Ultrasound every 6 months• U/S:Sensitivity 65‐80%, Spec >90%• Cost effective ‐ $2000/tumor found
![Page 40: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/40.jpg)
The Fight over AFP
![Page 41: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/41.jpg)
HCC Surveillance Utilization
• 13000 Vets 1998‐2005 HCV+ Cirrhotics– Only 12% had surveillance in first 3 yrs after dx
• 541 patients with diagnosis of HCC– 29% received annual surveillance prior to Dx
![Page 42: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/42.jpg)
Liver Mass in a Cirrhotic
![Page 43: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/43.jpg)
Diagnosis of HCC
![Page 44: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/44.jpg)
Biomarkers for HCC
• Makarem M. An overview of biomarkers for the diagnosis of HCC• Makarem M. Diagnostic significance of plasma osteopontin in HCC. Ann Hepatology. 2011
![Page 45: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/45.jpg)
Staging‐Guided Treatment
![Page 46: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/46.jpg)
Staging‐Guided Treatment
![Page 47: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/47.jpg)
Curative Treatment for HCC
![Page 48: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/48.jpg)
Surgical Resection
• Candidates– Non cirrhotic – Cirrhotic Childs A, without evidence of portal hypertension
– Single tumor– No size cut off (< 5 cm)
• 5 year survival 50% ‐ 70%• Recurrence > 70%
– Recurrence and De novo tumor
14
![Page 49: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/49.jpg)
Surgical Resection
MonthsMonths00
00Survival Probability (%
)Survival Probability (%
)
1212 2424 3636 4848
2020
100100
4040
6060
8080
6060 7272 8484 9696
Nl portal pressure, Bili <1
Portal pressure, Bili <1
Portal pressure, Bili 1
![Page 50: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/50.jpg)
Treatment of HCC
• Liver Transplantion– Milan Criteria
• 3 lesions all less than 3cm
• 1 lesion less than 5cm
• Mazzaferro V. NEJM. 1996• Bruix J. AASLD Guidelines 2010
![Page 51: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/51.jpg)
Loco‐Regional Therapy
• Ablation
17
![Page 52: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/52.jpg)
Palliative Treatments for HCC
![Page 53: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/53.jpg)
Chemoembolization and Radioembolization
![Page 54: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/54.jpg)
Treatment of HCC: Sorafenib• Pathogenesis of HCC is mediated by Raf‐1 and vascular endothelial growth factor (VEGF)
• Sorafenib (Nexavar) – Mechanism
• serine–threonine kinases inhibit Raf‐1 and B‐Raf • tyrosine kinase receptor activity of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3
– Inhibits tumor angiogenesis – Inhibits tumor‐cell proliferation– Increases apoptosis
![Page 55: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/55.jpg)
Sorafenib
![Page 56: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/56.jpg)
Sorafenib: Adverse EventsEvent Sorafenib (N=297) % Placebo (N=302) % P Value
Any Grade
Grade 3 Grade 4 Any Grade
Grade 3 Grade 4 Any Grade
Grade 3 or 4
Any Event 98 39 6 96 24 8 0.47 0.04
Diarrhea 55 10 <1 25 2 0 <0.001 <0.001
Fatigue 45 9 1 45 12 2 1.0 0.11
Abdominalpain
31 9 0 26 5 1 015 0.21
Weight loss
30 2 0 10 1 0 <0.001 .54
Anorexia 29 3 0 18 3 <1 0.001 1.00
Nausea 24 1 0 20 3 0 0.24 0.26
Hand foot skin reaction
21 8 0 3 1 0 <0.001 <0.001
22
![Page 57: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/57.jpg)
Sorafenib: Hand‐Foot Skin Reaction
• Anti‐angiogenic events typically occur during the first few weeks of treatment with varying degrees of desquamation
• Management– Topical treatment– Temporary or permanent dose reduction or suspension
23
Grade 1Incidence: 8%Grade 1Incidence: 8%
Grade 2 Incidence: 6% Grade 2 Incidence: 6%
Grade 3 Incidence: 8%Grade 3 Incidence: 8%
![Page 58: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/58.jpg)
Agents Beyond Sorafenib
![Page 59: Update on Hepatocellular Carcinoma€¦ · Internal Medicine Grand Rounds July 9th, 2013 Steve Scaglione, M.D. • Epidemiology • Pathogenesis • Surveillance • Diagnosis •](https://reader036.vdocuments.us/reader036/viewer/2022071215/60440f3da48a676a7e1d8f1a/html5/thumbnails/59.jpg)
Summary
• HCC is a major global public health problem affecting developing countries more than developed countries.
• It is largely driven by HBV and HCV epidemic • The largest risk factor is cirrhosis and HBV
– Surveillance saves lives!• The incidence of HCC is rising in the USA• Genetic studies are beginning to identify new targets for molecular therapeutics
• Early stage HCC can be cured• Late stage HCC has a poor prognosis