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1、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,2011,incidence,mortality,Age-standardized
2、 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),%,%,incidence,Age-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(Female)
3、,%,%,Age-standardized incidence rate(1/105),-Chen WQ,et al.Chin Cancer 2015;24(1):1-10,mortality,incidence,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 and alcohol consumptio
4、n 基因易感性 Genetic susceptibility syndromes,肿瘤相关病毒Viruses Associated with Cancer,VirusCancerHepatitis B,CHepatocellular CancerHIVKaposis sarcomaEpstein-Barr virus Nasopharyngeal cancerBurkitts lymphomaHuman Papilloma virusCervical cancer,肿瘤发病率与生活/环境因素Cancer Mortality&Behavior/environmental Factors,Fact
5、orPercentage 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(微量元素缺乏)等,吸烟相关肿瘤Smoking-related cancers,Lung cancer
6、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（Major Genes in Development of Cancer）,癌基因Oncogenes 抑癌基因Tumor suppressor genes DNA修复基因 DNA repair genes,癌基因Oncogenes,Growth factors 生长因子EGF,TGF-Growth factor receptors 生长
7、因子受体EGFR,PTK Intracellular transducers 细胞内传导素cAMP Transcription factors 转录因子c-myc,DNA修复基因失活,抑癌基因失活,癌基因激活,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 Cancer as a Long-term Process,癌前期,广泛播散期,侵袭期,原位癌期,Up to 1030 years,310 years,15 years,15
8、 years,肿瘤病理学The Pathology of Cancer,恶性肿瘤的命名 Nomenclature of Malignant Tumor,Names of tumorTissue of origin ExamplesCarcinomaEpithelium AdenocarcinomasSarcomaMesenchymal LiposarcomaMalig.lymphomaLymphocytes LymphomaMalig.melanomaMelanocytes Malignant melanomaMalig.Mesothelioma Mesothelium Pleural mal
9、ig.MesotheliomaTeratomaGerm Cells Testicular teratomaChoriocarcinomaTrophoblast Uterine choriocarcinoma,良性肿瘤Benign Tumors,A limited growth potential the neoplastic cells closely resemble those of the parent tissue(well diff.)growth slowly by expansion a well-encapsulated lesion do not usually produc
10、e serious effect,恶性肿瘤Malignant Tumors,proliferate rapidly more poorly differentiated cells progressive growth and invasion of the surrounding tissues metastases by lymphatic&blood vessels 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,有助于制订治疗方案
11、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Histopathological Staging&Classification,Adenocarcinomas Squamous carcinomas Small cell carcinomas Large cell carcinomas Sarcomas Lymphomas Leukemias Gliomas Seminomas Teratomas,恶性肿瘤特性The Hallmark of Malignancy,局部破坏性浸润Local destructive invasion 远处转
12、移Distant metastasis-the cardinal behavior to distinguish benign&malignant tumor,恶性肿瘤病理特征Pathological Features of Malignancy,an infiltrative uncapsulated margin invasion of baseline membrane or surrounding structure evidence of invasion of blood vessels or lymphatics or metastases tumor necrosis,arch
13、itecture abnormalities e.g.increased gland/stroma ratio cytological abnormalities e.g.increased nuclear/cytoplasm ratio numerous mitotic figures&abnormal mitoses,恶性肿瘤病理特征Pathological Features of Malignancy,癌的大体分型Gross Types of Carcinoma,Papillary,Nodular,Ulcerative,Cystic,Multiple,Diffuse,Stricture,
14、Borrmanns Classification,I 型,II型,III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 tissue by another Carcinoma in situ-the histological abnormalities are sufficiently severe to suggest carcinoma,but in the absence of basement membrane invasion Border
15、 tumor-A tumor with biologic behavior between benign and malignant,分化程度The Degree of Differentiation,高度分化(I级)Well differentiated 中度分化(II级)Moderately differentiated 低度分化(III级)Poorly differentiated,恶性肿瘤的后果Effects of Malignancy,Tumor arising within a hollow viscus梗阻 obstruction tumor arising from surfa
16、ce of organ溃疡/出血ulceration and bleeding,恶性肿瘤的波散Spread of Malignant Tumors,直接浸润(direct invasion)-rectal 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 G
17、C,T stage,Lymphatic Spread of Gastric Cancer,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转移簇(CAM 5.2100),肿瘤分期,国际癌症联盟（UICC）TNM分期T（tumor）：1，2，3，4，xN(lymph node)：1，2，3M(metastasis)：0，1临床分期（CTNM）术后的临床病理分期（PTNM）各种肿瘤的TNM分期标准是由各专业会议协定的,分期目的：制定合理治疗方案 正确评价治疗效果 判断预后 有利于交流,TNM 分期,T-原发肿瘤 primary tumorN-区域淋巴结regional l
18、ymph nodeM-远处转移metastases,癌症的诊断步骤The Diagnostic Procedures of Cancer,病史 History Family history Individual habits Social history Occupation Marital&Sex history Past history,体检 Physical Examination 系统体检 局部体检 TumorMetastatic foci,癌症的诊断步骤The Diagnostic Procedures of Cancer,特殊检查 Special Procedures Diagno
19、stic RadiologyChest X-raysBarium enema radiographyGastro-intestinal series radiographyArteriographyComputerized tomography(CT)Radioisotope scanning techniquesMammographyPositron emission tomography(PET),癌肿诊断步骤The Diagnostic Procedures of Cancer,特殊检查 Special Procedures Ultrasonic examination Endoscop
20、y Cytology Biopsybone-marrow biopsyneedle biopsyendoscopic biopsy Magnetic resonance imagine(MRI),癌肿诊断步骤The Diagnostic Procedures of Cancer,实验室检查(Lab Test)Routine test:blood,urine,stool Serum test:enzyme,hormoneglycoprotein,tumor markers Immunology test:AFP,CEA,tumor-related antigens Flow-cytometry(
21、FCM):DNA ploidyDNA index Gene Test:Oncogenes,DNA repair genesTumor suppressor genes,癌症诊断步骤The Diagnostic Procedures of Cancer,早期肿瘤诊断的工具Tools For Early Clinical Detection,Complete physical examination Regular mammography and breast self exam Haemoccult for occult blood in feces Urinanalysis and blood
22、 count A complete clinical history An in-depth family medical history,癌症的症状和体征Symptoms or Signs of Cancer,饮食习惯改变 Alteration 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Unexplai
23、ned 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 treatment,癌症的症状与体征Symptoms or Signs of Cancer,乳房癌 Breast Cancer,伴癌综合症Para-neoplastic Syndrome,Small cell carcinomas secret ACTHCushings syndrome Renal carcinomas secret erythropoitin
24、polycythaemia Mucin-secreting adenomas increasing the coagulability thromboembolism,恶液质Cachexia,肿瘤标记物Tumor Markers,Tumor 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-242,Barium Swallow,Borr-I,Borr-III,Borr-IV,Preoperative Staging by Spiral CT,螺旋CT显示肾脏肿瘤MSCT renal tumor,螺旋CT显示转移淋巴结
25、 MSCT Metastatic LN,内窥镜检查 Endoscopy,超声胃镜 Endoscopic Ultrasonography,EUS-T1,EUS-T2,EUS-T3,EUS-T4,MSCT-T1,MSCT-T2,MSCT-T3,MSCT-T4,MSCT-N1,MSCT-N2,MSCT-M1（Peritoneal Metastasis）,PET Imagingof GC,Detection 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,
26、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,癌痛缓解,强阿片类药物 非阿片类镇痛药辅助药物,疼痛持续或加重,弱阿片类药物 非阿片类镇痛 辅助药物,疼痛持续或加重,非阿片类药物辅助药物,疼痛发生,3,2,1,WHO癌症疼痛三阶梯给药原则,从小剂量开始视止痛效果渐增量口服为主无效时直肠给药最后才注射给药,90以上 满意正确的药物正确的剂量正确间隔时间正确用药途径,The Principles of Cancer Surgery,外科肿瘤学的基本原则,Principles of Cance
27、r Surgery,No involvement of surgical stumpSufficient lymphatic dissection(DnNn)No distant metastasesRemoval of involved adjacent organs and structures by combined en bloc resection,肿瘤外科治疗的关键问题Key Points of Cancer Surgery,Combined treatment modalities(Multiple disciplinary team,MDT)Preoperative chemo
28、therapy Postoperative chemotherapy Preoperative radiotherapy Postoperative radiotherapy Perioperative chemotherapy,辅助治疗 Adjuvant therapyAdministration of systemic therapy after optimal loco-regional therapy(surgery/radiotherapy)新辅助治疗 Neo-adjuvant therapyChemotherapy/Radiotherapy is administered prio
29、r to loco-regional therapy to reduce the tumor cell burden,Surgery,根据肿瘤位置局部LN组的清扫情况,LD/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 gr
30、eater lymph nodes.,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（en bloc resection),肿瘤治疗原则,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，否则极易复发或恶性变。恶性肿瘤:拟定综合治疗方案，在控制原发病灶后，进行转移灶的治疗。恶性肿瘤第一次治疗的正确与否对预后有密切关系。I期：手术为主。II期：局部治疗为主，原发肿瘤切除或放疗，并必须包括转移灶的治疗，辅以有效的全身化疗。III期：采取综合治疗，手术前、后及术中放疗或化疗。IV期：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Treatment Principl
31、es of Cancer Treatment are 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 par
32、ameter to measure survival and benefit of treatment-5-yr survival rates,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),肿瘤的分类与命名肿瘤的病理:发生发展过程,肿瘤细胞的分化 生长方式,转移
33、方式肿瘤的临床表现:局部表现肿瘤的主要诊断方法 肿瘤的三级预防肿瘤的治疗手段 外科治疗的原则,药物分类二 1)细胞毒素类药物；2)抗代谢类药；3)抗生素类；4)生物碱类；5)激素类；6)其他,静止期,药物分类一 1、细胞周期特异性 2、细胞周期非特异性3。细胞周期时相特异性,化 疗,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。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 DNA,Cytoplasm,mRNA,DNA,protein,S,G2,M,G1,G0,细胞周期与抗癌药物The Cell Cycle&Antic
34、ancer Drugs,抗代谢药物,抗细胞分裂药,长春碱类,泰素,化疗药物的分类Classification of Chemotherapeutic Drugs,ClassesExamplesAlkalating agents CisplatinAntimetabolites5-FU,MTXMitotic inhibitors VP-16,TaxoidsNatural products MMC,BleomycinOthersHydroxyurea,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Resistance to Chemotherapy,Decre
35、ased drug-activating enzymes Increased drug-inactivating enzymes Increased DNA repair Mutations in drug targets Excretion of drug out of the cells,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 to
36、xicity 心脏毒性 Cardiotoxicity 神经毒性 Neurotoxicity 生殖毒性与不育 Gonadal damage and sterility,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-f
37、low Technique,肿瘤放疗学基础The Principles of Radiotherapy,直线加速器A Linear Accelerator,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Radiotherapy Planning Process,Treatment deliverydose prescriptionimplementation of treatmentverificationmonitoring treatment Outcome,潜在的治疗靶点,
