Case Discussion <Case Presentation> A case of 55 yrs old male is admitted due to abdominal pain for 1month. He is a fisher and lived in tzyy-guan country. He is a vicitim of hepatitis C noted for 7 years. About 25 years ago, he ever received surgical operation due to perforated peptic ulcer and blood transfusion was performed then. Two years ago, suspected liver cirrhosis was told by local clinic. But he loss follow up and took Chinese herb drug by himself. Recently one month, he suffered from epigastric dull pain. Mild gastritis was impressed by endoscopy performed at local clinic. After medication, the pain still persisted. Abdominal sonography showed two liver tumors located in right lobe. He was transferred to our hospital and was admitted. During this admission, fine needle aspiration cytology was performed and hepatocellar carcinoma was suspected (class V). He also received dynamic abdominal CT and MRI examination. Hepatocelluar carcinoma (S5: 4cm and S8: 2cm) were impressed without ascites by these studies. There was no specific finding in the chest X ray and plain abdomen. Table 1. Hematologic laboratory values on admission WBC RBC Hb Hct MCV PLT K/μL M/μL  g/dL  % fL K/μL 4.1 3.45 10.4 29.1 84.3 97 Table 2. Blood chemical values on admission Total protein Alb Bil(T/D) AST ALT Alk-P r-GT BUN Cre LDH g/dL g/dL mg/dL U/L U/L  U/L U/L mg/dL mg/dL U/L 7.6 3.8 1.3/0.3 82  59 158 87 17.8 1.3 776 Chol TG  Na  K  AFP PT(P/C) INR  PTT(P/C) Stool OB mg/dL mg/dL  M M ng/mL Second R Second   89 121 137 4.0 1110 12.0/11.8 1.08 32.9/33.2 (-) Under the impression of hepatocelluar carcinoma, he received angiography. It showed two liver hypervascular tumors with suspected tumor thrombus in right anterior-superior portal vein branch. Transarterial chemoemoblization was carried our via right hepatic artery. After this TACE, he suffered from intermittent fever and mild abdominal pain for five days. When the condition is stable, he is discharged. <病案分析> 此病人為典型之hepatocellular carcinoma的case. 當病人可能因為於25年前輸血而得到C型肝炎,當肝炎經過一段時間後,出現肝硬化,但病人卻沒有定期追蹤,最後出現肝癌,肝癌最初並無症狀,就算此病人的肝癌已長至4公分合併有門靜脈右前分支的轉移,卻仍無特別典型症狀,在台灣對於這種屬於肝癌高危險群的病人,臨床醫師應小心警慎的追蹤並且衛教病人. 肝癌的診斷對於病人來說是很大的衝擊,若能在肝癌早期就診斷出來,對於預後會有很大的幫助,但是如何在超音波,abdominal CT, MRI以及angiography上正確區分出肝癌,甚至是小型的肝癌,避免誤診,目前仍是許多醫師所要學習的課題. 目前對於肝癌的治療,除開刀外,仍有很多的選擇,TACE(transarterial chemoembolization)是能延長病人生命及生活品質的有效方法,但是仍有許多的不足及須注意的禁忌症. 當無法施行TACE時, local abration therapy是我們應該要考慮的治療方法. 繼續教育考題 1. (E) Which one is not correct of the following? A There is high incidence of HCC (more than 20 per 100000 per year) in Taiwan. B Macronodular cirrhosis is more commonly associated with hepatitis B virus (HBV) infection, and is more prone to hepatocarcinogenesis. C There is 3-6.5% of patients with HCV cirrhosis develop HCC annually. D Hepatocellular carcinoma growth in the bile duct system is not rare; it was seen in 10% of autopsy cases. E All of the above are correct. 2. (A) Where is the most common metastatic site of HCC? A Lung B Adrenal gland C Bone D Pancreas E Brain 3. (E) Which one is not correct about small HCCs? A Increased celluarity with an increased nucleus/cytoplasm ratio and increased staining affinity.(eosinophilic or basophilic) B Irreular, thin trabecular pattern, with frequent pseudoglandular or acinar structures. C Frequent fatty changes. D Small HCC less than 2 cm in size are often found as hyperechoic lesions, because fatty changes are common in extremely well-differentiated early lesions. It make the differential diagnosis from hemangioma difficult. E All of the above are correct 4. (D) Which one of laboratory finding is not the character of HCC ? A AST is higher than ALT. B AFP > 1000 ng/mL. C Elevated des-r-carboxy prothrobin (DCP). D Elevated amylase/lipase. E Elevated r-GT. 5. (B) On angiography, which one may be presented and specific to arteries within a tumor thrombus? A "C-sign" B "thread-and-streaks sign" C "cotton and wool sign" D Vascular displacement E Arterioportal shunts 6. (C) Which one is not the sign of HCC on angiography? A Hypervascularity B Neovasculatrue C "C-sign" D Displacement of large arteries E Encasement of large arteries 7. (A) What stage is the case classified by Okuda staging? A I B II C III D IV E None of the above 8. (E) Which one is not correct about MRI presentation of HCC? A Except for some early, well-differentiated tumors, HCC usually is of higher intensity than the parenchyma on T2-weighted images, but its intensity on T1 images varies with tumor grade and biochemical composition. B In encapsulated HCC, the fibrous capsule is shown as hypointense on both T1- and T2-weighted images. C Gadolinium chelates is used as contrast agent for dynamic MRI. D Dynamic MRI with gadolinium chelates shows finding similar to those of dynamic CT using ionic contrast media. E All of the above are correct. 9. (A) What is the contraindication for targeted chemoembolization (TACE)? A Child C reserved liver function. B PT prolong = 2 sec C WBC< 5000 /μL D HB < 10 mg/dL E Tumor size > 5cm 10. (D) Which one is not the local abration therapy for HCC? A Pure ethanol injection therapy. B Radiofrequency coagulation therapy. C Percutaneous acetic acid injection therapy. D Intra-arterial chemotherapy. E Microwave coagulation therapy. 答案解說 (E) 台灣是B型肝炎的高盛行區, 罹患B型肝炎的患者, 較正常人易進行到Macronodular cirrhosis, 也比較容易得到肝癌, 所以台灣也是屬於肝癌的高盛行區, 會侵犯到膽道的肝癌並不算少數, 可以在10%左右autopsy的case中發現. C型肝炎且合併肝硬化的患者大約每年有3-6.5%會罹患肝癌. (A) 肝癌患者最常見的轉移區域, 以肺部最常見. 但bone, brain, pancreas, adrenal gland也很常見. (E) 小型肝癌(< 2cm)在超音波下可能呈現低超音波(hypoechoic),但也可能呈現高超音波(hyperechoic),這是因為肝癌細胞常合併有脂肪性的變化(fatty change)所致, 在組織學上, 可見到肝癌細胞的nucleus/cytoplasm ratio增加, 細胞數,及染色性也較正常肝細胞增加. 細胞的排列也呈現不規則較纖細的索狀排列,有時常會出現假性的腺體樣排列(Pseudoglandular or acinar structures). (D ) 當amylase/lipase升高時,應該先懷疑胰臟的病灶, 除非當肝癌轉移到胰臟, amylase/lipase才有可能會升高. (B ) Encasement of artery: 當腫瘤不斷的增生時, 可能會將動脈包埋起來, 在angiography上會呈現有一段動脈突然變細, 然後又變粗. “thread-and-streaks sign”: 當腫瘤長進大血管管腔之中形成血栓時,供應腫瘤的小血管也一起長進去, 在angiography的artery phase時會呈現數條平行條紋的小血管及高血管性的腫瘤染色, 有時會類似掃帚樣的圖樣. “cotton-wool sign”: 由於hemangioma的血管是由腫瘤外圍慢慢供應擴散進來, 在angiography上會呈現像棉花樣或羊毛樣的染色. Vascular displacement: 當腫瘤不斷的增生時, 可能會將旁邊的動脈推開, 而偏離原來的走向. Arterioportal shunts: 肝癌或肝硬化的患者, 在angiography的artery phase時, 常可見到portal vein已經被顯影出來, 就是因為arterioportal shunt所造成. (C) “cotton-wool sign”: 是hemangioma的特徵. (A) 根據上述資料, 此位患者: tumor size < 50% of liver=> (-) no ascites => (-) Alb > 3g/dl => (-) Bil < 3mg/dl => (-) Okuda stage的四項標準中, 都為陰性, 所以okuda staging為I. (E) 典型HCC的MRI表現, T2 phase是high intensity tumor, 但是在T1 phase中則不一定, 具有capsule的HCC在T1, T2 phase時, 其capsule為hypointense, 若使用Gadolinium為contrast的dynamic MRI, HCC也會像dynamic CT一樣,呈現early enhacement的腫瘤樣表徵. (A) 病人的reserved liver function為Child C時,若貿然進行TACE,會有hepatic failure的risk. (D)Intra-arterial chemotherapy是屬於局部的動脈化療注射, 並非local abration therapy.