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1、外科肿瘤学外科肿瘤学Surgical Oncology肿瘤的定义Definition of Tumor 肿瘤是机体中正常细胞, 在不同的始动与促进因素长期作用下所产生的增生与异常分化所形成的新生物 Tumors are characterized by cells that have lost their normal control mechanisms and thus have unregulated growth The top 10 cancer incidence and mortality in China, 2011incidencemortalityAge-standardi
2、zed incidence rate (1/105) - Chen WQ, et al. Chin Cancer 2015; 24(1):1-10 The top 10 cancer incidence and mortality in China, 2011(Male)%incidenceAge-standardized incidence rate (1/105) - Chen WQ, et al. Chin Cancer 2015; 24(1):1-10 mortality% The top 10 cancer incidence and mortality in China, 2011
3、 (Female)%Age-standardized incidence rate (1/105) - Chen WQ, et al. Chin Cancer 2015; 24(1):1-10 mortalityincidence 肿瘤病因学肿瘤病因学The Etiology of Cancer 病毒 Viruses (papilloma, Epstein-Barr, Hepatitis B, retroviruses, HIV) 射线 Radiation exposure 环境、工业因素Environmental industrial carcinogens 吸烟/饮酒 Tobacco an
4、d alcohol consumption 基因易感性 Genetic susceptibility syndromes肿瘤相关病毒肿瘤相关病毒Viruses Associated with CancerVirusCancerHepatitis B, CHepatocellular CancerHIVKaposis sarcomaEpstein-Barr virus Nasopharyngeal cancerBurkitts lymphomaHuman Papilloma virusCervical cancer 肿瘤发病率与生活肿瘤发病率与生活/ /环境因素环境因素Cancer Mortal
5、ity & Behavior/environmental FactorsFactorPercentage of cancer deathsSmoking30Diet30Infectious agents 5Alcohol 3Sedentary lifestyle 3Ultraviolet 2Air pollution 2人体内在因素( Inherent Factors)1. 遗传因素: 遗传易感性(hereditary susceptibility)2. 内分泌因素: 某些激素代谢紊乱可诱发或促进 肿瘤生长3. 免疫因素: 机体免疫功能降低, 肿瘤发病率升高4. 其它因素: 精神, 营养 (
6、微量元素缺乏) 等吸烟相关肿瘤吸烟相关肿瘤Smoking-related cancers Lung cancer Oropharyngeal cancer Stomach cancer Cervical cancer Pancreatic cancer Renal cancer Bladder cancer Liver cancer Leukemia 与肿瘤发生相关的基因与肿瘤发生相关的基因 （Major Genes in Development of Cancer） 癌基因Oncogenes 抑癌基因Tumor suppressor genes DNA修复基因 DNA repair gene
7、s癌基因癌基因Oncogenes Growth factors 生长因子EGF, TGF- Growth factor receptors 生长因子受体EGFR, PTK Intracellular transducers 细胞内传导素cAMP Transcription factors 转录因子c-mycDNA修复基因失活修复基因失活抑癌基因失活抑癌基因失活癌基因激活癌基因激活癌细胞癌细胞肿瘤的发生和发展恶性肿瘤病因和发病机制模式图 结直肠肿瘤发生的遗传模型肿瘤的发生经历了一系列遗传学上的变化，如数个癌基因的激活和/或抑癌基因的失活，及其他基因变化。Modern Viewpoint of C
8、ancer as a Long-term Process癌前期癌前期广泛播散期广泛播散期侵袭期侵袭期原位癌期原位癌期Up to 1030 years310 years15 years15 years肿瘤病理学肿瘤病理学The Pathology of Cancer 恶性肿瘤的命名恶性肿瘤的命名 Nomenclature of Malignant TumorNames of tumorTissue of origin ExamplesCarcinomaEpithelium AdenocarcinomasSarcomaMesenchymal LiposarcomaMalig. lymphomaLy
9、mphocytes LymphomaMalig. melanomaMelanocytes Malignant melanomaMalig. Mesothelioma Mesothelium Pleural malig. MesotheliomaTeratomaGerm Cells Testicular teratomaChoriocarcinomaTrophoblast Uterine choriocarcinoma良性肿瘤良性肿瘤Benign Tumors A limited growth potential the neoplastic cells closely resemble tho
10、se of the parent tissue ( well diff.) growth slowly by expansion a well-encapsulated lesion do not usually produce serious effect恶性肿瘤恶性肿瘤Malignant Tumors proliferate rapidly more poorly differentiated cells progressive growth and invasion of the surrounding tissues metastases by lymphatic & blood ve
11、ssels if not treated early, eventually cause death Peritoneal carcinomatosis of gastric cancer癌肿分期和组织学分类的目的癌肿分期和组织学分类的目的 有助于制订治疗方案 有助于判定预后 有助于评判疗效 有助于资源共享和学术交流 有助于癌肿临床研究的开展组织病理学分期与分类组织病理学分期与分类Histopathological Staging & Classification Adenocarcinomas Squamous carcinomas Small cell carcinomas Large c
12、ell carcinomas Sarcomas Lymphomas Leukemias Gliomas Seminomas Teratomas恶性肿瘤特性恶性肿瘤特性The Hallmark of Malignancy 局部破坏性浸润Local destructive invasion 远处转移Distant metastasis- the cardinal behavior to distinguish benign & malignant tumor恶性肿瘤病理特征恶性肿瘤病理特征Pathological Features of Malignancy an infiltrative unc
13、apsulated margin invasion of baseline membrane or surrounding structure evidence of invasion of blood vessels or lymphatics or metastases tumor necrosis architecture abnormalities e.g. increased gland/stroma ratio cytological abnormalities e.g. increased nuclear/cytoplasm ratio numerous mitotic figu
14、res & abnormal mitoses恶性肿瘤病理特征恶性肿瘤病理特征Pathological Features of Malignancy 癌的大体分型癌的大体分型Gross Types of CarcinomaPapillaryNodularUlcerativeCysticMultipleDiffuseStrictureBorrmanns ClassificationI 型型 II型型III型型型型左肺上叶中央型肺癌胃癌肝转移Three Important Terms Metaplasia - the replacement of one fully differentiated t
15、issue by another Carcinoma in situ - the histological abnormalities are sufficiently severe to suggest carcinoma , but in the absence of basement membrane invasion Border tumor - A tumor with biologic behavior between benign and malignant 分化程度分化程度The Degree of Differentiation 高度分化( I级 ) Well differe
16、ntiated 中度分化( II级 ) Moderately differentiated 低度分化( III级 ) Poorly differentiated恶性肿瘤的后果恶性肿瘤的后果Effects of Malignancy Tumor arising within a hollow viscus梗阻 obstruction tumor arising from surface of organ溃疡/出血ulceration and bleeding恶性肿瘤的波散恶性肿瘤的波散Spread of Malignant Tumors直接浸润 ( direct invasion ) - rec
17、tal cancer 区域淋巴结转移( lymphatic spread )- breast carcinoma, gastric cancer 血行播散至远处( metastasis by bloodstream ) - liver, lung & brain 体腔内种植 ( cavity implantation ) - ovarian carcinoma (Krukenbergs tumor)TNM Staging of GCT stage are defined by depth of penetration into the gastric wallLamina propriaT1a
18、T1bT4aT4bT3Subserosal connective tissueT1bT1aT4aT4bT stage Lymphatic Spread of Gastric Cancer淋巴结内单个癌细胞转移灶淋巴结内单个癌细胞转移灶(CAM 5.2100)淋巴结内数个癌细胞形成的淋巴结内数个癌细胞形成的转移簇转移簇 (CAM 5.2100)肿瘤分期肿瘤分期国际癌症联盟（国际癌症联盟（国际癌症联盟（国际癌症联盟（UICCUICC） TNMTNM分期分期分期分期T T（tumortumor）：）：）：）：1 1，2 2，3 3，4 4，x xN (lymph node)N (lymph node
19、)：1 1 ，2 2 ，3 3M(metastasis)M(metastasis)：0 0，1 1临床临床临床临床分期（分期（分期（分期（CTNMCTNM）术后的术后的术后的术后的临床病理临床病理临床病理临床病理分期（分期（分期（分期（PTNMPTNM）各种各种各种各种肿瘤的肿瘤的肿瘤的肿瘤的TNMTNM分期标准是由各专业会议协定的分期标准是由各专业会议协定的分期标准是由各专业会议协定的分期标准是由各专业会议协定的分期目的：分期目的：分期目的：分期目的： 1.1.制定合理治疗方案制定合理治疗方案制定合理治疗方案制定合理治疗方案 2.2.正确评价治疗效果正确评价治疗效果正确评价治疗效果正确评价治
20、疗效果 3.3.判断预后判断预后判断预后判断预后 4.4.有利于交流有利于交流有利于交流有利于交流TNM 分期分期T- 原发肿瘤 primary tumorN- 区域淋巴结regional lymph nodeM- 远处转移metastases癌症的诊断步骤癌症的诊断步骤The Diagnostic Procedures of Cancer病史病史 History Family history Individual habits Social history Occupation Marital & Sex history Past history体检体检 Physical Examinati
21、on 系统体检系统体检 局部体检局部体检 TumorMetastatic foci 癌症的诊断步骤癌症的诊断步骤The Diagnostic Procedures of Cancer特殊检查特殊检查 Special Procedures Diagnostic RadiologyChest X-raysBarium enema radiographyGastro-intestinal series radiographyArteriographyComputerized tomography(CT)Radioisotope scanning techniquesMammographyPositr
22、on emission tomography(PET)癌肿诊断步骤癌肿诊断步骤The Diagnostic Procedures of Cancer特殊检查特殊检查 Special Procedures Ultrasonic examination Endoscopy Cytology Biopsybone-marrow biopsyneedle biopsyendoscopic biopsy Magnetic resonance imagine (MRI)癌肿诊断步骤癌肿诊断步骤The Diagnostic Procedures of Cancer实验室检查实验室检查 ( Lab Test
23、) Routine test: blood, urine, stool Serum test:enzyme, hormoneglycoprotein, tumor markers Immunology test:AFP, CEA, tumor-related antigens Flow-cytometry(FCM):DNA ploidyDNA index Gene Test: Oncogenes, DNA repair genesTumor suppressor genes 癌症诊断步骤癌症诊断步骤The Diagnostic Procedures of Cancer早期肿瘤诊断的工具早期肿瘤
24、诊断的工具Tools For Early Clinical Detection Complete physical examination Regular mammography and breast self exam Haemoccult for occult blood in feces Urinanalysis and blood count A complete clinical history An in-depth family medical history癌症的症状和体征癌症的症状和体征Symptoms or Signs of Cancer 饮食习惯改变 Alteration
25、 in eating habit 食欲下降 Loss of appetite 吞咽困难 Problems in swallowing 排便习惯改变 Change in bowel habit 局部肿块 The presence of a lump at any site 出血The appearance of bleeding 反复疼痛Unexplained recurrent pain 反复发热Recurrent fevers 消瘦Unexplained weight loss 反复难治性感染 Repeated infections which do not clear with treat
26、ment癌症的症状与体征癌症的症状与体征Symptoms or Signs of Cancer乳房癌乳房癌 Breast Cancer伴癌综合症伴癌综合症Para-neoplastic Syndrome Small cell carcinomas secret ACTHCushings syndrome Renal carcinomas secret erythropoitinpolycythaemia Mucin-secreting adenomas increasing the coagulability thromboembolism恶液质恶液质Cachexia肿瘤标记物肿瘤标记物Tum
27、or MarkersTumor markerExamples肿瘤抗原AFP, CEA酶PSA激素-HCG癌基因Ras, c-myc肿瘤相关抗原CA 19-9,CA-242Barium SwallowBorr-IBorr-IIIBorr-IVPreoperative Staging by Spiral CT螺旋螺旋CT显示肾脏肿瘤显示肾脏肿瘤MSCT renal tumor螺旋螺旋CT显示转移淋巴结显示转移淋巴结 MSCT Metastatic LN内窥镜检查内窥镜检查 Endoscopy超声胃镜超声胃镜 Endoscopic UltrasonographyEUS-T1EUS-T2EUS-T3E
28、US-T4MSCT-T1MSCT-T2MSCT-T3MSCT-T4MSCT-N1MSCT-N2MSCT-M1（Peritoneal Metastasis）PET Imagingof GCDetection of Peritoneal Metastasis by Laparoscopy肿瘤的预防( Prevention of Tumor)三级预防的概念:一级预防: 环境因素包括饮食习惯的改造与 预防, 减少致癌因素, 降低癌肿发生率二级预防: 强调早期发现, 早期诊断, 早期治疗三级预防: 改善生活质量, 对症处理, 减轻病痛 延长患者生命世界卫生组织三阶梯止痛方案 癌痛缓癌痛缓解解 强阿片类药
29、物强阿片类药物 非阿非阿片类镇痛药片类镇痛药辅助药物辅助药物疼痛持续或加重疼痛持续或加重疼痛持续或加重疼痛持续或加重 弱阿片类药物弱阿片类药物 非阿非阿片类镇痛片类镇痛 辅助药物辅助药物疼痛持续或加重疼痛持续或加重疼痛持续或加重疼痛持续或加重 非阿片类药物非阿片类药物辅助药物辅助药物 疼痛发生疼痛发生疼痛发生疼痛发生 3 32 21 1WHO癌症疼痛三阶梯给药原则癌症疼痛三阶梯给药原则 从小剂量开始从小剂量开始从小剂量开始从小剂量开始视止痛效果渐增量视止痛效果渐增量视止痛效果渐增量视止痛效果渐增量口服为主口服为主口服为主口服为主无效时直肠给药无效时直肠给药无效时直肠给药无效时直肠给药最后才注射
30、给药最后才注射给药最后才注射给药最后才注射给药9090以上以上以上以上 满意满意满意满意正确的药物正确的药物正确的药物正确的药物正确的剂量正确的剂量正确的剂量正确的剂量正确间隔时间正确间隔时间正确间隔时间正确间隔时间正确用药途径正确用药途径正确用药途径正确用药途径The Principles of Cancer Surgery外科肿瘤学的基本原则外科肿瘤学的基本原则Principles of Cancer SurgeryNo involvement of surgical stumpSufficient lymphatic dissection (DnNn)No distant metasta
31、sesRemoval of involved adjacent organs and structures by combined en bloc resection肿瘤外科治疗的关键问题肿瘤外科治疗的关键问题Key Points of Cancer Surgery Combined treatment modalities ( Multiple disciplinary team, MDT) Preoperative chemotherapy Postoperative chemotherapy Preoperative radiotherapy Postoperative radiothe
32、rapy Perioperative chemotherapy辅助治疗辅助治疗 Adjuvant therapyAdministration of systemic therapy after optimal loco-regional therapy (surgery/ radiotherapy)新辅助治疗新辅助治疗 Neo-adjuvant therapyChemotherapy/Radiotherapy is administered prior to loco-regional therapy to reduce the tumor cell burdenSurgery根据肿瘤位置局部
33、LN组的清扫情况D14d4d4d653D211p12a14v1998a97LD/L Surgical treatment for gastric cancer Gastric resection should include the regional lymphatic - perigastric lymph nodes (D1) and those along the named vessels of the celiac axis (D2), with a goal of examining 15 or greater lymph nodes.腹腔镜结肠癌手术腹腔镜结肠癌手术腹腔镜结肠癌手
34、术腹腔镜结肠癌手术腹腔镜结肠吻合技术 胃癌手术标本整块切除胃癌手术标本整块切除 （en bloc resection)肿瘤治疗原则肿瘤治疗原则良性肿瘤及交界性肿瘤良性肿瘤及交界性肿瘤良性肿瘤及交界性肿瘤良性肿瘤及交界性肿瘤: : 以手术切除为主。尤其交界性肿瘤必须切除，以手术切除为主。尤其交界性肿瘤必须切除，以手术切除为主。尤其交界性肿瘤必须切除，以手术切除为主。尤其交界性肿瘤必须切除，否则极易复发或恶性变。否则极易复发或恶性变。否则极易复发或恶性变。否则极易复发或恶性变。恶性肿瘤恶性肿瘤恶性肿瘤恶性肿瘤: : 拟定综合治疗方案，在控制原发病灶后，进行转移灶的治拟定综合治疗方案，在控制原发病灶
35、后，进行转移灶的治拟定综合治疗方案，在控制原发病灶后，进行转移灶的治拟定综合治疗方案，在控制原发病灶后，进行转移灶的治疗。恶性肿瘤第一次治疗的正确与否对预后有密切关系。疗。恶性肿瘤第一次治疗的正确与否对预后有密切关系。疗。恶性肿瘤第一次治疗的正确与否对预后有密切关系。疗。恶性肿瘤第一次治疗的正确与否对预后有密切关系。I I期：期：期：期：手术为主。手术为主。手术为主。手术为主。IIII期：期：期：期：局部治疗为主，原发肿瘤切除或放疗，并必须包括转移灶局部治疗为主，原发肿瘤切除或放疗，并必须包括转移灶局部治疗为主，原发肿瘤切除或放疗，并必须包括转移灶局部治疗为主，原发肿瘤切除或放疗，并必须包括转
36、移灶的治疗，辅以有效的全身化疗。的治疗，辅以有效的全身化疗。的治疗，辅以有效的全身化疗。的治疗，辅以有效的全身化疗。IIIIII期：期：期：期：采取综合治疗，手术前、后及术中放疗或化疗。采取综合治疗，手术前、后及术中放疗或化疗。采取综合治疗，手术前、后及术中放疗或化疗。采取综合治疗，手术前、后及术中放疗或化疗。IVIV期：期：期：期：有全身治疗为主，辅以局部对症治疗。有全身治疗为主，辅以局部对症治疗。有全身治疗为主，辅以局部对症治疗。有全身治疗为主，辅以局部对症治疗。肿瘤治疗方案制订的基础肿瘤治疗方案制订的基础Treatment Principles of Cancer Treatment a
37、re Based Upon 肿瘤生物学特性 治疗手段的并发症发生率和死亡率 治疗手段的效果 病人生活质量肿瘤治疗方案制订的基础肿瘤治疗方案制订的基础Treatment Principles of Cancer Treatment are Based Upon with localized cancers are curable presenting with positive Lymph Nodes tend to bad outcome with distant metastases are rarely curable the most commonly parameter to meas
38、ure survival and benefit of treatment-5-yr survival rates肿瘤治疗新手段肿瘤治疗新手段New Approaches to Cancer Immunology Biological response modifiers Interferons and interleukins Adoptive immunotherapy Monoclonal antibodies Tumor vaccines Gene therapy本课重点(key points)1.肿瘤的分类与命名2.肿瘤的病理: 发生发展过程, 肿瘤细胞的分化 生长方式, 转移方式3
39、.肿瘤的临床表现: 局部表现4.肿瘤的主要诊断方法 5.肿瘤的三级预防6.肿瘤的治疗手段 外科治疗的原则药物分类二药物分类二药物分类二药物分类二 1)1)1)1)细胞毒素类药物；细胞毒素类药物；细胞毒素类药物；细胞毒素类药物；2)2)2)2)抗代谢类药；抗代谢类药；抗代谢类药；抗代谢类药；3)3)3)3)抗生素类；抗生素类；抗生素类；抗生素类；4)4)4)4)生物碱类；生物碱类；生物碱类；生物碱类；5)5)5)5)激素类；激素类；激素类；激素类；6)6)6)6)其他其他其他其他增殖周期增殖周期 M G1 G0 G2 S 静止期静止期 药物分类一药物分类一 1、细胞周期特异性、细胞周期特异性 2
40、、细胞周期非特异性、细胞周期非特异性3。细胞周期时相特异性。细胞周期时相特异性 化化 疗疗l细胞毒药物: 依赖肿瘤细胞与正常细胞生长、修复、死亡的动力学间的差异来杀伤肿瘤细胞，选择性差。l靶向治疗：具有针对致癌机制，直接攻击致癌 病因，选择性强Antisense DNACytoplasmmRNADNAproteinSG2MG1G0细胞周期与抗癌药物细胞周期与抗癌药物The Cell Cycle & Anticancer Drugs抗代谢药物抗代谢药物抗细胞分裂药抗细胞分裂药长春碱类长春碱类泰素泰素化疗药物的分类化疗药物的分类Classification of Chemotherapeutic
41、DrugsClassesExamplesAlkalating agents CisplatinAntimetabolites5-FU, MTXMitotic inhibitors VP-16,TaxoidsNatural products MMC, BleomycinOthersHydroxyurea肿瘤负荷越大肿瘤负荷越大 治疗周期越多 耐药克隆越多 生长指数越小 转移可能越大 肿瘤化疗耐药性肿瘤化疗耐药性Resistance to Chemotherapy Decreased drug-activating enzymes Increased drug-inactivating enzym
42、es Increased DNA repair Mutations in drug targets Excretion of drug out of the cells化疗药物的不良反应化疗药物的不良反应Chemotherapy-induced Toxicities 骨髓抑制 Bone marrow suppression 免疫抑制 Immunosuppression 恶心呕吐 Nausea and vomiting 脱发 Alopecia 肾肺毒性 Renal , pulmonary toxicity 心脏毒性 Cardiotoxicity 神经毒性 Neurotoxicity 生殖毒性与不
43、育 Gonadal damage and sterility肿瘤化疗发展方向肿瘤化疗发展方向New Approaches of Chemotherapy 新药物 New drug- Taxol, Topo II Inhibitors 生化调节剂 Biomodulation- Leucovorin/5-FU 围手术期化疗 Peri-operative chemotherapy-Neoadjuvant chemotherapy 区域性化疗 Loco-regional chemotherapy- IPHC , Stop-flow Technique肿瘤放疗学基础肿瘤放疗学基础The Principl
44、es of Radiotherapy直线加速器直线加速器A Linear Accelerator放疗方案的制订放疗方案的制订Radiotherapy Planning Process Pre-planningTNM stagingRadical vs palliative intent Treatment planningdescription of treatmentpatient immobilizationdefinition of tumor volumestechnique and beam modificationcalculation of dose distribution肿瘤放疗方案肿瘤放疗方案Radiotherapy Planning Process Treatment deliverydose prescriptionimplementation of treatmentverificationmonitoring treatment Outcome潜在的治疗靶点潜在的治疗靶点
