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1、,Complain:right quadrant pain intermittently for 2 months.Concomitant:anorexia usually and diarrhea occasionallyP.E:no special signBlood-RT:normalStool-RT:normalPast-H:HBV infection for 20 ys.Family-H:mother died of HBV-cirrhosis,Diagnosis?,A case:,Male,41 y.o.,Hepato-Cellular Carcinoma(HCC)!,Hepato
2、-Cellular Carcinoma(HCC),Chang-qing Yang,MD&PhD,Tongji Hospital of Tongji University,同济大学附属同济医院杨长青,Special Terms,Hepatocellular Carcinoma(HCC)肝细胞癌 Aflatoxin 1 黄曲霉素B1-Fetoprotein(AFP)甲胎球蛋白-Glutamyl Transferase(-GT)-谷氨酰转移酶-L-Fucosidase(ALF)-盐藻糖苷酶 Des-Carboxy Prothrombin(D-CP)脱羧基凝血酶原 Hepatomegaly肝肿大TAC
3、E(transarterial chemoembolization)介入化疗,Background:HCC,most common solid organ tumor worldwideincidence is rising:USA 2.4/100,000 China 20.4/100,000 South Africa 60/100,000in China,marginal waters hinterland eastern western one million died annually,Top 2 in tumors,Sex distribution,Male：Female=35：1 i
4、n ChinaAlmost equal in developed countries,Age distribution,Middle aged man in predominance(43.7 y)It is rare in childrenIt rises progressively with age,although it tends to level off in the oldest age group,Etiology&Pathogenesis,Four major causal associations of HCC The etiologic agents differs wit
5、h different area,Risk factors,Major Chronic HBV infectionChronic HCV infectionAflatoxin 1Liver fibrosis&Cirrhosis,Hepatitis B virus,Chronic infection with HBV may cause as much as 80%of human HCC It is closest in ethnic Chinese and black Africans Early infection carries a greater risk,HBV&HCC,Hepati
6、tis B Virus,HBV DNA could be integrated into cellular DNA in about 95%of patients with HBV-related tumorsThe site of integration is randomIntegration perturbing the function of cellular oncogenes or tumor suppressor genes,which may contribute to hepatocellular carcinogenesis,Hepatitis C Virus,HCV is
7、 carcinogenic in humanIn Japan,Italy,Spain,chronic HCV infection is the major risk factor for hepatocellular carcinomaA far smaller percentage of ethnic Chinese and black African have HCV-induced tumorsHCV does not integrate into host DNA,its mechanism differs from that of HBV,HCV&HCC,Developed coun
8、tries:50%-70%Developing countries:13.3 38.5%,HCV(+)in HCC,HCV&HCC,Cirrhosis,HCC frequently coexists with cirrhosis(80%),Cirrhosis,HCC,Cirrhosis,In ethnic Chinese and black Africans,it is usually of the macronodular variety and is the result of chronic HBV infection,In other populations,it is commonl
9、y of the micronodular variety and is usually caused by alcohol abuse,or both,Aflatoxin 1,It is a major risk factor for HCC in certain geographic regionsEpidemiologic studies have shown a positive correlation between intake of aflatoxin 1 and the incidence of HCC,Main Risk Factors,The main risk facto
10、rs of HCC are _?,Progress,HCC,Clin Liver Dis.2005;9(2):281-5 Gastroenterology.2004;127(5 Suppl 1):S79-86,Minor risk factors,As many as 45%of persons who suffer from hereditary hemochromatosis develop into HCCThis complication was thought to occur only in the presence of cirrhosisPatients with Wilson
11、 disease occasionally develop into HCC,although only in the presence of cirrhosisOther inherited metabolic disturbances predispose to that HCC may also induced by cirrhosis(1antitrypsin deficiency),Minor Risk Factors,In patients with the use of contraceptive steroids,the risk is related directly to
12、the duration of useControversy exists over whether cigarette smoking,Pathology,Gross appearance Microscopic appearance Well-Differentiated appearance Moderate-Differentiated appearance Undifferentiated appearance Fibrolaminar hepatocellular carcinoma,Gross appearance,Nodular or=5cm,most common form
13、most prone to rupture Diffuse It is rare,may be difficult to distinguish from regenerating nodules of cirrhosis,Gross appearance,Nodular Type,Gross appearance,Massive Type,Gross appearance,Diffuse Type,Small HCC,3cmWell differentiated,low grade malignancyUsually encapsulated cancer embolism rate is
14、low with relative good liver function,Microscopic appearance,Hepatocyte(90%)Bile duck cell(less)Mixed(least),Metastasis of HCC,Intrahepatic metastasis:through portal vein Extrahepetic metastasis:through hepatic vein or lymph route 5 most common sites of HCC metastasis are:(1)regional lymph nodes(2)l
15、ung(3)adrenal glands(4)bone(5)peritoneal surface,Metastasis of HCC,Intrahepatic metastasis:,Metastasis of HCC,Extrahepetic metastasis:,Tumor embolus in inferior cava vein,HCC,Clinical manifestation,Symptoms Prevalence(%)Abdominal pain 59-95Weight loss 34-71Weakness 22-53Abdominal swelling 28-43Nonsp
16、ecific 25-28Gastrointestinal symptoms common,Clinical manifestation,Physical signs Prevalence(%)Hepatomegaly 54-98Hepatic bruit 6-25Ascites 35-61Splenomegaly 27-42Jaundice 4-35Wasting 25-41Fever 11-54,Paraneoplastic Syndromes associated with HCC,HypoglycemiaPolycythemia(erythrocytosis)HypercalcemiaO
17、steoporosisPolymyositisNeuropathy,Sexual changes:gynecomastia feminization,Clinical stages,Stage I(subclinical stage):High risk factors,hepatitis history or HBsAg+over 5 years No specific symptoms Elevated AFP Single or multiple nodules,size=5cm No vascular invasion,Clinical stages,Stage IIa Present
18、 some symptoms or signs of HCC Abnormal laboratory findings Single or double nodules 510cm No portal vein cancerous embolism No lymph nodes enlargement No distant metastasis,Clinical stages,Stage IIb Single or double nodules 10cm or triple 10cm in one hepatic lobule Single or double nodules 510 cm i
19、n two hepatic lobule Portal vein cancerous embolism,Clinical stages,Stage III More advanced than stage IIb or with vascular invasion or with intrahepatic invasion or with peritoneal lymph nodes enlargement or distant metastasis,Complications,Hepatic encephalopsy end stage deadly complication,1/3 dea
20、th cause Gastrointestinal bleeding esophageal varices,erosive GI mucosa Rupture of hepatic cancer mass accounts for 914%Secondary infection,Laboratory tests and others,Tumor markers of HCC Radiologic investigations Needle biopsy,Tumor markers,-Fetoprotein(AFP)Glutamyl Transferase(-GT)L-Fucosidase(AL
21、F)Des-Carboxy Prothrombin(D-CP),-Fetoprotein(AFP),high concentration in fetal serum,in normal adult usually500g/L)is a strong pointer to the diagnosis of HCC Below this level may be found in patients with variety of acute and chronic benign hepatic disease or GI tumor with liver metastasis,Glutamyl
22、Transferase(-GT),Normal serum contains as many as 10 isoenzymes of-GTThree isoenzymes may be present in serum from patients with HCC:-GT-I 27%-GT-II 60%-GT-III 30%,Des-Carboxy Prothrombin,It is raised in the majority of patients with HCC 250g/L is considered positive,L-Fucosidase(ALF),It was first r
23、eported to have a sensitivity of 75%and specificity 90%in HCCIn a subsequent study,it failed to distinguish between cirrhosis and HCCIn black Africans,this marker is less sensitive,less specific and has lower predictive value than alpha-fetoprotein,Tumor markers,Sensitivity(%)Specificity(%)Advantage
24、s DisadvantagesAFP 8090(high)90 Relatively quick Relative easy to measure expansive D-CP 58-91 84 Easy and quick Far more to measure expansiveALF 75 70-90 Easy and quick to measure,relative inexpansive-GT-II 60 96 Relatively easy and Expansive quick to measure,Hepatic imaging,Ultrasonography(U-S)Com
25、puted Tomography(CT)Magnetic Resonance Imaging(MRI)Hepatic Arteriography(DSA)Position emission computed tomography(PECT),Ultrasonography,Detects tumor which size 2cmShows the size,sharp,site and its relationship with vesselIdentifies the hepatic vein,portal vein cancerous embolismDoppler sonography
26、are useful,Ultrasonography,Ultrasonography,CT,It usually shows the tumor size greater than 2.0 cmIt may detect small HCC(1.0 cm)by using contrast materials It is the best method for detecting small and micro HCC,CT,CT,MRI,Useful for detecting both primary and tumor spreadUseful in distinguishing bet
27、ween small HCC and small hemangiomas uncovered during surveillance,MRI,MRI,Hepatic arteriography,It is the best modality for detecting the tumor site It may show tumor with 0.5cm1.0cm,Hepatic arteriography,Hepatic arteriography,PET(positron emission tomography),Peritoneoscopy,(Laparoscopy),Liver bio
28、psy,Diagnosis,Diagnosis,HCC markers,Hepatic imaging,HCC!,Risk Factors,Clinical Manifestation,Diagnosis,HCC markers,Hepatic imaging,Sub-clinical HCC!,Risk Factors,Clinical Manifestation,Differential Diagnosis,Hepatic cirrhosis/hepatitis Secondary liver cancer Benign hepatic tumors Liver abscess,Treat
29、ment,Treatment,Surgical resection Alcohol injection Embolization and chemoembolization(TACE)Chemotherapy Physiotheropy Liver transplantation,Surgical resection,Offers the best chance for cure of HCC,Surgical resection,Alcohol Injection,also called percutaneous ethanol injection(PEI)too small to be s
30、uitable for resection or because they are multiple or because their special position in the liver or because of the severe hepatic dysfunction It carries the risk of disseminating the tumor,Alcohol injection,Embolization/TACE,Embolization with lipiodol and anticancer drugs has been used to reduce th
31、e viable tumor mass before surgeryPatients receiving TACE(transarterial chemoembolization)may survival longer than untreated patients,Embolization/TACE,Chemotherapy,A large number of anticancer agents can be employedThe predictable response rate has always been less than 20%Current trials are invest
32、igating the use of agents that reverse multidrug resistance,Physiotherapy,Microwave melt(微波熔瘤),Physiotherapy,RFA,radiofrequency ablation(射频消融),Liver transplatation,Tumor is not amenable to resectionTumor has no extrahepatic metastasisNo HBV or HCV infection,Liver transplantation,Prognosis of Transplant,good survival with transplant for tumors 5cm，75%at 4 yearspoor survival with transplant for tumors 5cm，18-30%at 5 years,Question,How would you establish the diagnosis of HCC?,Thank You!,杨长青同济大学附属同济医院 消化科,
