1、原发性肝癌Primary liver Cancer 一、肝癌的流行病学1. 肝癌的发病率: 南非60100/100,000 亚洲35/100,000，最高达40/100,0002. 其它流行病学特点： 男女发病：38：1 中青年发病率高，平均年龄43.7岁二、肝癌的发病机理1.病毒性肝炎： 亚州肝癌患者7090为HBV携带者，国内肝癌患者HBV携带者超过85。2.肝硬化3.化学致癌剂二、肝癌的发病机理二、肝癌的发病机理1.病毒性肝炎2.肝硬化 7085%的肝癌发生于肝硬化时肝细胞代偿增生的基础上。3.化学致癌剂二、肝癌的发病机理1.病毒性肝炎2.肝硬化3.化学致癌剂 在肝癌高发地区，黄曲霉素B
2、1(AFB1）的污染程度较重，检出率高，AFB1能导致肝细胞损害，肝细胞修复、增生过程中可能发生癌变。其他化学致癌物还包括：亚硝胺类化合物、有机氯杀虫剂。最常见，多伴肝硬化，常为多个结节，大小不一，分布广泛，有半数以上病例波及全肝。多为单个癌结节或多个癌结节融合而成，较少肝硬化，切除机会多。n巨块型：n结节型：三、肝癌的分型及分期1.根据大体标本观察：传统分为小肝癌、大肝癌及巨大肝癌n弥漫型：少见，为广泛分布的小结节癌灶，肉眼下难与结节性肝硬化区分。三、肝癌的分型及分期2.根据病理细胞学：n肝细胞型n胆管细胞型n混合型I 级：癌细胞的形态接近正常，常与II级并存。II 级：癌细胞核比正常者大，
3、着色深，胞浆呈嗜酸性和明显的颗粒状，常见腺泡并含胆汁。III级：胞核更大，更富有染色质而着色更深，胞浆少，仍有颗粒，呈嗜碱性，胆汁很少发现，癌巨细胞多见。IV级：胞核大而深染，胞浆很少，胞浆中颗粒或有或无，条索结构不易见到。n 亚临床前期n 临床前期：从亚临床肝癌诊断建立至出现症状之前，患者仍无症状与体征，瘤体约35cm，诊断仍较困难，多属AFP普查发现，此期平均为8个月左右。n 亚临床前期：从病变开始至作出亚临床肝癌诊断之前，患者无症状与体征，临床难以发现，平均10个月。4. 分期n 亚临床前期n 临床前期n 临床期：一旦出现临床症状，已至中期。此时病情发展迅速，不久可出现黄疸、腹水、肺转移
4、已至广泛转移及恶病质的晚期表现，中、晚期共6个月时间，肝癌发展至晚期，瘤体可达10cm左右，治愈困难。3.根据恶性程度：IIV级三、肝癌的分型及分期四、肝癌的转移途径n肝内播散：通过门静脉肝内播散。 n血行转移：通过肝静脉，多转移至肺部。 n淋巴转移：肝门部淋巴结转移多见，晚期可转移至胰、脾、主动脉旁、锁骨上淋巴结等。 n直接侵犯和腹腔播种五、肝癌的临床表现n早期肝癌的非特异性症状 早期症状较为隐匿，表现无特征性。由于多合并有肝硬化，更容易被忽视，早期症状有上腹部不适、胀痛、刺痛、食欲下降、乏力。五、肝癌的临床表现n肝癌的典型症状 1.肝区疼痛 2.全身和消化道症状3.肝肿大持续性钝痛、刺痛或
5、胀痛，可反射至右肩背部。癌结节坏死、破裂、出血引起右上腹剧痛、压痛。 早期不引人注意，主要表现为乏力、消瘦、食欲减退、腹胀，部分病人可有恶心、呕吐、发热、腹泻等症状，晚期出现贫血 、黄疸、腹水、下肢浮肿、皮下出血及恶病质。中晚期肝癌最常见的体征，约占95，肝进行性肿大，导致右侧膈肌抬高、肝浊音界上升。在部分病人，肝区包块及肝肿大为首发症状。 六、肝癌的诊断n早期诊断是原发性肝癌获得早期治疗的前提，一旦肝癌出现了典型症状与体征，诊断并不困难，但往往已非早期。所以，凡是中年以上，特别是有肝病史病人，发现有肝癌早期非特异的临床表现，应考虑肝癌的可能。n特征性：慢性肝病史、肝占位性病变，甲胎蛋白 六、
6、肝癌的诊断1. 血清学检测： AFP：为目前诊断肝细胞癌特异性最高的方法之一，阳性率6090。对无肝癌其它证据，血清AFP放射免疫400g/L，持续一个月以上，并能排除妊娠，活动性肝病，生殖腺胚胎性肿瘤等即可诊断为肝细胞癌。 其它：-谷氨酰转肽酶，硷性磷酸酶和乳酸脱氢酶等由于缺乏特异性，多作为辅助诊断。六、肝癌的诊断2.影像学检查B超:可显示肿瘤的大小，形态，所在部位以及肝静脉或门静脉内有无癌栓等，其诊断符合率可达84%，能发现直径2厘米或更小的病变，是目前较好有定位价值的非侵入性检查方法。六、肝癌的诊断2.影像学检查CT CT :分辨率高，可检出直径约1厘米左右的早期肝癌，应用增强扫描有助与
7、血管瘤鉴别。对于肝癌的诊断符合率高达90%。多排螺旋CT定位准确有利于手术方案设计。六、肝癌的诊断2.影像学检查血管造影:对血管丰富的癌肿，有时可显示直径为0.51厘米的占位病变,其诊断正确率高达90%。可确定病变的部位、大小和分布，特别是对小肝癌的定位诊断是目前各种检查方法中最优者。但属有创检查，必要时才考虑采用。六、肝癌的诊断2.影像学检查核磁共振成象:诊断价值与CT相仿，可获得横断面、冠状面和矢状面图象，对良、恶性肝占位病变，特别是与肝血管瘤的鉴别优于CT，且无需增强即可显示肝静脉和门静脉。并对肝内管道系统有无癌栓作出判断。六、肝癌的诊断2.影像学检查放射性核素扫描；ECT有助于诊断大肝
8、癌。但不易发现小于3cm的肿瘤六、肝癌的诊断3.肝活检n穿刺活检：肝穿刺行针吸细胞学检查有确定诊断意义，目前多采用在B型超声引导下行细针穿刺，有助于提高阳性率，但有导致出血，肿瘤破裂和针道转移等危险。七、肝癌的鉴别诊断n肝血管瘤:无肝炎病史、CT可见典型的早到迟退现象，AFP阴性。 n肝硬变：鉴别困难，依靠AFP，活检及定期观察。 n继发性肝癌：病情进展较缓慢，有原发病的改变，AFP阴性，典型的转移病灶为牛眼征改变。n肝脓肿：感染表现，AFP阴性，血象升高，抗感染治疗有效。n肝包虫病：牧区生活史或牛羊狗接触史，Cassoni实验阳性，CT可见子囊，边界清楚。 n肝脏邻近器官肿瘤：AFP，必要时
9、行剖腹探查。 阿米巴性及细菌性肝脓肿鉴别细菌性肝脓肿细菌性肝脓肿阿米巴性肝脓肿阿米巴性肝脓肿病病 史史继发于胆道感染继发于胆道感染继发于肠阿米巴痢疾继发于肠阿米巴痢疾病病 程程病情急骤严重，全身病情急骤严重，全身脓毒血症明显脓毒血症明显起病较缓慢，病程较长，起病较缓慢，病程较长，症状较轻症状较轻血液化验血液化验WBCWBC计数增加，中性计数增加，中性粒细胞可高达粒细胞可高达90%90%。有时血培养阳性有时血培养阳性白细胞计数可增加，血液白细胞计数可增加，血液细菌培养阴性细菌培养阴性粪便检查粪便检查无特殊发现无特殊发现可找到阿米巴滋养体可找到阿米巴滋养体脓肿穿刺脓肿穿刺多为黄白色脓液，涂多为黄白
10、色脓液，涂片和培养发现细菌片和培养发现细菌多为棕褐色脓液，镜检有多为棕褐色脓液，镜检有阿米巴滋养体。阿米巴滋养体。诊断性治疗诊断性治疗抗生素治疗有效抗生素治疗有效抗阿米巴治疗好转抗阿米巴治疗好转脓肿脓肿较小，多发较小，多发较大，多单发肝右叶较大，多单发肝右叶八、肝癌的治疗原则1.早期发现、早期诊断及早期治疗并根据不同病情发展阶段进行综合治疗，是提高疗效的关键。2.早期施行手术切除仍是最有效的治疗方法。3.对无法手术的中、晚期肝癌，可根据病情进行栓塞、冷冻、中医中药治疗和化疗。适应征：一、患者一般情况适应征：一、患者一般情况1.患者一般情况较好，无明显心、肺、肾等患者一般情况较好，无明显心、肺、
11、肾等重要脏器器质性病变。重要脏器器质性病变。2.肝功能正常，或仅有轻度损害，按肝功能肝功能正常，或仅有轻度损害，按肝功能分级属分级属级；或肝功能分级属级；或肝功能分级属级，经短期级，经短期护肝治疗后有明显改善，肝功能恢复到护肝治疗后有明显改善，肝功能恢复到级级.3.肝储备功能（如肝储备功能（如ICG,R15）正常范围。）正常范围。4.无广泛肝外转移性肝癌癌灶肿瘤。无广泛肝外转移性肝癌癌灶肿瘤。八、肝癌的治疗1.手术治疗：八、肝癌的治疗n二、局部病变情况二、局部病变情况（一）下述病例可作根治性肝切除（一）下述病例可作根治性肝切除1.单发的微小肝癌（直径单发的微小肝癌（直径2cm）。）。2.单发的
12、小肝癌（直径单发的小肝癌（直径2cm, 5cm）。）。3.单发的向肝外生长的大肝癌（直径单发的向肝外生长的大肝癌（直径5cm, 10cm）或巨大肝癌（直径）或巨大肝癌（直径10cm.），表面较光滑，周围界限较清楚，受），表面较光滑，周围界限较清楚，受癌灶破坏的肝组织少于癌灶破坏的肝组织少于30%。4.多发性肝癌，癌结节少于多发性肝癌，癌结节少于3个，且局限在肝脏个，且局限在肝脏的一段或一叶内。的一段或一叶内。八、肝癌的治疗n（二）下述病例仅可行姑息性肝切除：（二）下述病例仅可行姑息性肝切除：1. 3-5个多发性肿瘤，超越半肝范围者，作多处个多发性肿瘤，超越半肝范围者，作多处局限性切除；或肝癌局
13、限于相邻局限性切除；或肝癌局限于相邻2-3个肝段或半个肝段或半肝内，影像学显示，无瘤侧肝脏组织明显代偿性肝内，影像学显示，无瘤侧肝脏组织明显代偿性增大，达全肝的增大，达全肝的50%以上。以上。2.左半肝或右半肝的大肝癌或巨大肝癌，边界较左半肝或右半肝的大肝癌或巨大肝癌，边界较清楚，第一、二肝门未受侵犯；影像学显示，无清楚，第一、二肝门未受侵犯；影像学显示，无瘤侧肝脏明显代偿性增大，达全肝组织的瘤侧肝脏明显代偿性增大，达全肝组织的50%以上。以上。3.位于肝中央区（肝中叶，或位于肝中央区（肝中叶，或、段）的段）的大肝癌，无瘤肝脏组织明显代偿性增大，达全肝大肝癌，无瘤肝脏组织明显代偿性增大，达全肝
14、的的50%以上。以上。八、肝癌的治疗n（二）下述病例仅可行姑息性肝切除（二）下述病例仅可行姑息性肝切除 4或或段的大肝癌或巨大肝癌。段的大肝癌或巨大肝癌。5 肝门部有淋巴结转移者，如原发性肝脏肝癌肝门部有淋巴结转移者，如原发性肝脏肝癌可切除，应作肿瘤切除，同时进行肝门部淋巴结可切除，应作肿瘤切除，同时进行肝门部淋巴结清扫；淋巴结难以清扫者，术后可进行放射治疗。清扫；淋巴结难以清扫者，术后可进行放射治疗。6周围脏器（结肠、胃、隔肌或右肾上腺等）周围脏器（结肠、胃、隔肌或右肾上腺等）受侵犯，如原发性肝脏肿瘤可切除，应连同作肿受侵犯，如原发性肝脏肿瘤可切除，应连同作肿瘤和侵犯脏器一并切除。远处脏器单
15、发转移性肿瘤和侵犯脏器一并切除。远处脏器单发转移性肿瘤（如单发肺转移），可同时行原发肝癌切除和瘤（如单发肺转移），可同时行原发肝癌切除和转移癌切除术。转移癌切除术。 八、肝癌的治疗2.介入治疗：经肝动脉内给予含化学药物的栓塞剂进行肝动脉栓塞化疗，可使肝癌缩小，部分病人可因此而获得二期手术切除的机会，少数患者可以达到治愈。采用经股动脉插管超选择性肝动脉造影定位下，行肝动脉栓塞化疗，具有可以反复多次施行的特点。3.无水酒精注射:在B超引导下经皮肝穿刺肿瘤无水酒精注射或术中无水酒精注射,能使肿瘤脱水、凝固、坏死，适用于瘤体较小而又不能或不宜手术切除者，一般需要重复注射数次。八、肝癌的治疗八、肝癌的治
16、疗4.冷冻治疗：对于较小的肿瘤或无法切除的肿瘤，可以通过液氮或氩氦刀冷冻治疗，通过细胞冻融使肿瘤细胞破坏，达到治疗或减积的目的。八、肝癌的治疗5.热凝固治疗:通过微波或射频，在肿瘤局部产生高温使肿瘤凝固变性，达到治疗肝癌或肝癌减积的目的，其适应症与冷冻治疗相同。八、肝癌的治疗6.放射治疗7.化学治疗8.免疫治疗9.中医中药治疗九、小结n肝癌的发病率逐年提高，有年轻化的趋势。n诊断方法、治疗方法多样。n随着原发性肝癌的早期诊断、早期治疗和肝脏外科的发展，肝癌的总体治疗效果显著提高。n以针对患者的个体化综合治疗效果较好。A 21-year-old man presented with a 2-mo
17、nth history of weight loss, night sweats and early satiety. Physical exam revealed hepatomegaly, shown on this caudal view of the upper abdomen. nThe abdominal scout film shows the size of the liver, predominantly a markedly enlarged right lobe The CT scan shows a 20X15cm right lobe mass. There was
18、no evidence of extrahepatic tumor on the abdominal CT, and CT of the chest and bone scan were both normal. Core needle biopsy of the mass showed non-fibrolamellar hepatocellular carcinoma. Upper endoscopy and colonoscopy were normal. Bilirubin was 0.7 and liver enzymes were normal. Hepatitis serolog
19、ies were normal. Alphafetoprotein was over 230,000. nMagnetic resonance angiogram showed no anomalous left or right hepatic arteries nThe patient was taken to the operating room for exploration and possible right hepatic lobectomy. nA right subcostal (Kocher) incision was made first, exposing the bu
20、lging right lobe. nExploration showed no evidence of metastatic disease nThe chevron incision was completed, and the lower flap tacked down to lower abdominal skin. nThe hepatoduodenal ligament (surgeons left index finger in foramen of Winslow) was palpated, and there was no significant adenopathy n
21、The xiphoid extension was completed. nA self-retaining retractor was placed. nThe periphery of the right lobe was mobilized by dividing adhesions to the transverse mesocolon. nWith the right lobe elevated, the porta hepatis was exposed. nThe gastrohepatic omentum was divided, isolating the hepatoduo
22、denal ligament containing hepatic artery, common bile duct and portal vein. nThe gallbladder was removed. nIntraoperative ultrasound was performed, revealing no evidence of disease in the left lobe. nThe hepatic artery was isolated and encircled with a red vessel loop. nThe portal vein was dissected
23、, and a venous branch from the caudate lobe was ligated and divided. nThe right branch of the portal vein was isolated and encircled with a blue vessel loop. nThe right hepatic artery was ligated and divided. nThe right portal vein was clamped with vascular clamps and divided. nThe cut end of the ri
24、ght portal vein was oversewn with running 5-0 polypropylene suture. nThe liver is shown after division of the right portal vein and right hepatic artery. nThe right triangular ligament (see hepatic anatomy) was divided nThe right lobe was mobilized. nThe inferior vena cava was exposed at the dome of
25、 the diaphragm. The forceps is on the right hepatic vein. nThe duodenum was Kocherized, exposing the infrahepatic inferior vena cava. nThe right hepatic vein is seen in the top CT slice, and the large inferior right branch is shown in the lower slice. nA large branch of the inferior group of hepatic
26、 veins was isolated. nThe large branch was ligated on the liver side, and clamped on the vena cava side. nAfter division and oversewing of the branch, another large branch was revealed behind. nThe second branch was divided in similar fashion. nThe right hepatic vein was isolated. nThe right hepatic
27、 vein was divided with a linear vascular stapler. nSmaller short hepatic branches were divided, freeing the right anterolateral wall of the inferior vena cava. nThe right lobe was fully mobilized nUmbilical tape was passed behind the liver, to mark the plane between vena cava and gallbladder bed del
28、ineating the division of right and left lob nDivision of the devascularized right lobe was begun anteriorly using electrocautery. nThe plane of dissection was kept to the left of the middle hepatic vein (see hepatic segmental anatomy) because of the proximity of that structure to the tumor. Vascular
29、 connections between segment IV and the right lobe were isolated and divided between clips. nAn argon beam coagulator was used to aid surface hemostasis. nThe partially divided interlobar plane is shown. nThe ultrasonic dissector/aspirator was used to further develop the plane nThe middle hepatic ve
30、in was divided at its junction with the left hepatic vein. nThe last connections of the right lobe are shown from the patients left. The connections, including the right hepatic duct, were divided and the specimen removed. nThe abdomen is shown after removal of the specimen. nThe lateral surface of the right lobe is shown (caudal to left, posterior to top). nThe abdomen was closed in standard fashion
