内科学课件-肝癌

1、HEPATOCELLULAR CARCINOMABACKGROUND肝癌是全世界最常见的恶性肿瘤之一，排名第八位。在我国恶性肿瘤发病率中占第二位。以肝区疼痛、纳差、乏力、消瘦、黄疸为基本临床表现。早期病人以手术为首选治疗方法，临床大部分病人属中、晚期，以非手术治疗为主。平均生存期3-6个月。EPIDEMIOLOGY全世界每年新发原发性肝癌约26万例，占恶性肿瘤4，我国约占其中42.5。各国肝癌发病率有较大的差异。在欧、美大部分地区、北非和中东部是罕见肿瘤。在西、中和东非，肝癌是主要恶性肿瘤；在南非和东南亚是第二位常见恶性肿瘤。肝癌男性发病率高于女性，2.6:1。19901992年我国抽样地区6

2、2种肿瘤的粗死亡率（1/10万）与死亡构成（%）节选TOPOGRAPHIC ANATOMY肝脏位于右上腹，是人体最大的腺体。外观上分为左叶、右叶、方叶和尾叶。肝脏有四套管状系统：肝动脉、门静脉、肝静脉、胆管系统。PATHOLOGY原发性肝癌据细胞起源分为： 肝细胞癌（最多见，占90%） 胆管细胞癌 混合细胞癌 肝肉瘤大体分型：结节型、巨块型、弥漫型小肝癌的概念：小于3cm，数目不超出两个。METASTASIS肝内转移门脉转移血行转移淋巴转移腹腔种植CLINICAL PRESENTATION早期多无明显症状。出现临床症状时多为晚期。主要症状有：肝区疼痛、黄疸、腹胀、呕吐、消化不良、腹泻、纳差、乏

3、力、消瘦、出血等。体征DIAGNOSTIC WORK-UP (1)甲胎球蛋白(AFP)：是部分胚胎细胞所产生的一种蛋白。在胎儿及出生后一段时间较高。正常成人血中浓度2g/L。甲胎球蛋白对69.1的肝细胞癌和13.5的胆管细胞癌有诊断作用。其他引起AFP增高的因素有妊娠、生殖系统肿瘤、畸胎瘤等，临床上应通过细心体检和必要的检查加以排除。 (2)超声检查：可见肝内强或弱回声光团，肿块周围有一片晕团，肿块内回声不均等表现可以确定肝内占位病变的存在，提示或确定病灶性质，定位并活检。确定肿块播散及转移，甚至通过带孔探头行局部注药。在普查中与观结合使用，可提高诊断率。 (3)CT：是肝癌诊断中最主要的手段

4、之，能反映肝癌的病理形态表现，如病灶大小、形态、部位、数目、病灶内有无出血坏死、钙化等，从病灶边缘可了解其浸润性，从门脉血管的癌栓和受侵犯情况了解其侵犯性。CT平扫可见肿块呈不规则低密度，周围有一层更低密度环影；碘剂增强后早期病灶增强，持续10-30秒后与肝组织等密度，再以后成为低密度，可持续数分钟。增强尚可为门脉，腔静脉受累提供依据。(4)血管造影：可借助于普通x线机，DSA机。肝动脉造影的x线表现如下：肿瘤血管、肿瘤染色、肝内动脉移位、扭曲、拉直或扩张，肿瘤包绕动脉，动静脉痪，“他样”或“湖样”造影剂充盈区，肝内充盈故损或不规则斑驳区。(5)其他：有定性、定量价值的检查有-谷氨酰转移酶、碱

5、性磷酸酶、醛缩酶同功酶、-抗胰蛋白酶、异常疑血酶原、铁蛋白、运铁蛋白、血浆神经紧张素、绒毛膜促性腺激素、丙酮酸激酶同功酶、胎盘型谷胱甘肽转移酶、MR等。DIAGNOSTIC 病理诊断： 肝组织学检查证实为原发性肝癌； 肝外组织的组织学检查证实为肝细胞癌。 临床诊断标准 2001年中国抗癌协会肝癌专业协会修订的原发性肝癌临床诊断标准：AFP大于或等于400g/L ，能排除妊娠、活动性肝病、生殖腺胚胎源性肿瘤及转移性肝癌等，并能触及肿大坚硬及有结节状肿块的肝脏或影像学检查有肝癌特征的占位性病变者。(2) AFP大于或等于400g/L ，能排除妊娠、活动性肝病、生殖腺胚胎源性肿瘤及转移性肝癌等，并有

6、两种影像学检查有肝癌特征的占位性病变者；或有两种肝癌标志物（DCP、GGT-2、AFU、CA19-9）阳性及一种影像学检查有肝癌特征的占位性病变者。(3)有肝癌的临床表现，并有肯定的远处转移灶（包括肉眼可见的血性腹水或者在其中发现癌细胞），并能排除转移性肝癌者。TNM Classification of Malignant Tumours, Sixth EditionRegional Lymph NodesThe regional lymph nodes are the hilar, hepatic (along the proper hepatic artery), periportal (

7、along the portal vein) and those along the abdominal inferior vena cava above the renal veins (except the inferior phrenic nodes).T Primary Tumour TX. Primary tumour cannot be assessed T0. No evidence of primary tumour T1. Solitary tumour without vascular invasion T2. Solitary tumour with vascular i

8、nvasion or multiple tumours, none more than 5cm in greatest dimension T3. Multiple tumours more than 5cm or tumour involving a major branch of the portal or hepatic vein(s) T4. Tumour(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum N R

9、egional Lymph Nodes NX. Regional lymph nodes cannot be assessed N0. No regional lymph node metastasis N1. Regional lymph node metastasis M Distant Metastasis MX. Distant metastasis cannot be assessed M0. No distant metastasis M1. Distant metastasis Summary ：LiverStage GroupingGENERAL TREATMENTNCCN G

10、UIDELINES 2005RADIOTHERAPY肝脏的放射敏感性： 限制放疗的姑息作用的主要原因是肝对3-4周内的25-30Gy以上的放射不能耐受。来自纪念医院和斯坦福大学的资料表明，放疗导致的肝炎，其中大多数病例是使用35Gy或35Gy以上的全肝放射时发生，而低于38.5Gy放射剂量不会发生持续性或致命性肝炎。肝脏的小部分放疗可以耐受50-60Gy，而无明显的远期并发症。肝脏的放射敏感性尚受下列因素影响(1)损伤：如手术切除，使肝细胞由静止状态转为增殖状态，放射敏感性增加。(2)肝硬化：硬化肝脏的放射耐受量明显下降。(3)放疗合并化疗：位肝的放射损伤加重。RADIATION TECHNI

11、QUES设野有全肝野、条形野、局部野。全肝野、条形野现已基本不用。局部野指照射野紧扣肿瘤边界。一般前后左右外放1cm，上下界充分考虑呼吸移动因素。放射剂量全肝不超过30Gy/4周，目前常用肿瘤剂量为50-60Gy/6-8周。3DCRTThe goal of 3DCRT is to precisely target the tumor(s) and to reduce damage to the surrounding normal tissue. Respiratory excursion affects the precision of radiation. the tumor shifte

12、d between the two respiratory phases: The variation ranged from 2.6 to 23.7 mm: from 0.4 to 5.9 mm in the lateral direction, 2.2 to 24.5 mm in the longitudinal direction, and 0.2 to 11.7 mm in the vertical direction.Breath-gating or breath-holding technique may help overcome the problem of respirato

13、ry movement during irradiation.The radiation-field margin to the target in the lateral direction should be 6 to 9 mm, vertical direction should be 9 to 12 mm, superior direction should be 10 mm, and inferior direction should be 19 to 21 mm. Combining TACE and Local Radiation Therapy TACE alone rarel

14、y produces complete pathologic remission for HCC larger than 5 cm, especially in the peripheral zone of the tumor. Additional therapy theoretically is required to eradicate the residual disease. The combination of TACE and conformal radiotherapy shows promising results in large HCC. FIGURE 53.2. A:

15、A 55-year-old man with hepatitis B virus (HBV) infection developed a large hepatocellular carcinoma in the right lobe of the liver. The tumor measured 12 15 15 cm. -fetoprotein (AFP) was 901 ng/mL. B: After a first course of transcatheter arterial chemoembolization (TACE), his AFP dropped to 150 ng/mL. It rose to 440 ng/mL 3 months later. He had a second TACE followed by three-dimensional conformal radiotherapy. This image was taken after the second TACE, revealing viable tumors in