外科学总论课件：cancer

1、2021-6-21 2021-6-21 An altered cell population characterized by an excessive, nonuseful proliferation of cells that have become unresponsive to normal control mechanisms and to the organizing influences of adjacent tissues. 2021-6-21 Benign tumor Malignant tumor (Cancer) vCarcinoma vSarcoma Borderin

2、g tumor 2021-6-21 Essentials of Moledular Biology: Genomics and Cancer Essentials of Signal Transduction Essentials of Immunology 2021-6-21 Molecular Biology of Cancer: Oncogenes vIdentification of Oncogenes and Tumor Suppressor Genes vFunction of Oncogenes and Tumor Suppressor Genes 2021-6-21 MSH2,

3、 hMLH1, PMS1, PMS2 2021-6-21 2021-6-21 2021-6-21 2021-6-21 高通量分析技术高通量分析技术Tissue Array Tissue Array 2021-6-21 2021-6-21 检测大肠癌及转移灶的不同组织基因表达研究 正常组织、结肠癌及癌旁组织 肝转移组织及淋巴结转移灶 FAP的不同部位的组织块 高通量分析技术高通量分析技术基因芯片基因芯片( (Gene Chip)Gene Chip) 基因芯片技术日益成熟，在生命科学领域的应用更为广泛 Gene PM MM Oligo 2021-6-21 Telomerase, Cell Agin

4、g and Cancer Time Telomere Length Critical Telomere Length Normal Cells Stem & Tumor Cells 2021-6-21 Cytogenetics The Cell Cycle Apoptosis Angiogenesis Invasion and Metastasis 2021-6-21 2021-6-21 2021-6-21 2021-6-21 2021-6-21 正 常 粘 膜 I 癌转 移 APCK-rasDCCP53nm23?其它 甲基化 5q 突变 . 缺失 12p 突变 18q 突变 ? 缺失 17p

5、 突变 . 缺失 IIIIIIV Adenoma MCC hMSH2 hMLH1 hPMS1 hPMS2 ACF COX-2 SNC6，SNC73 SNC19，maspin，osteo ACF Genotype：APC突变突变13 exon 2/6 12 exon 4/6 p53、p21突变突变 DCC突变突变 Phenotype：不典型增生不典型增生 2001,6 2001,6 月，月，DublinDublin 内外因相互作用研究内外因相互作用研究 2021-6-21 2021-6-21 Viruses (DNA and RNA Viruses) Chemical Factors Physi

6、cal Factors Hormonal Factors Cancer Genetics (Hereditary factors) 2021-6-21 肿肿 瘤瘤 发发 生生 机机 制制 环 境、饮食 生物性因素 遗传易感性 酶的多态性 基因不稳定 MSI Intereaction DNA损伤 修 复 修 复 DNA突变 癌变 染色体不稳定 作用后出现的分子产物 （基因与蛋白） 2021-6-21 Cancer as a Genetic Disease Mechanisms of Cancer Predisposition Clinical Characteristics of Cancer

7、Families Multisystem Genetic Syndromes With a High Risk of Cancer Nonsyndromic Hereditary Cancer 2021-6-21 Human Carcinogenesis: The Nature of the Evidence Cancer Epidemiology by Site An Overview of Cancer Causes 2021-6-21 Preventing Tobacco-Related Cancers Diet and Chemopreventive Agents: vFat: Bre

8、ast Cancer, Colon Cancer, Prostate Cancer and other Cancer vDietary Fibers vRetinoids, Carotenoids, and Micronutrients vNaturally Occurring Dietary Anticarcinogens vDietary Carcinogens vAspirin and Other Nonsteroidal Antiinflammatory Drugs and the Risk of Cancer Development vPhysical Activity and Bo

9、dy Weight vRole of Surgery in Cancer Prevention 2021-6-21 What is Cancer Screening? Evaluation of A screening Test Breast Cancer Screening Cervical Cancer Screening Skin Cancer Screening Prostate Cancer Screening Colorectal Cancer Screening Lung Cancer Screening 2021-6-21 Carcinogenesis and Tumorige

10、nesis Tumor cell differentiation Growth pattern Growth rate (speed) Metastasis vDirect Extension vLymphatic Spread vVascular Spread vSpread through Serous Cavities 2021-6-21 Immunohistochemistry DNA Content Diagnostic Molecular Genetics Techniques in the Molecular Genetic Diagnosis of Cancer Molecul

11、ar Markers in Cancer Diagnosis Small Mutations Future Expectations 2021-6-21 Cancers seven warning signals vChange in bowel or bladder habits vA sore that does not heal vUnusual bleeding or discharge vThickening or lump in breast or elsewhere vIndigestion or difficulty in swallowing vObvious change

12、in wart or mole vNagging cough or hoarseness 2021-6-21 Mass Pain Ulcer Bleeding Obstruction Metastatic Manifestations 2021-6-21 2021-6-21 2021-6-21 2021-6-21 Non-specific: v Anemia v Low fever v Weight loss v Inertia Anorexia-cachexia and others 2021-6-21 2021-6-21 Diagnosis of cancer should proceed

13、 in on orderly fashion: vCareful history (Details of risk factors including family history and current medication should be noted in the patients records) vThorough physical examination vLaboratory examination vImaging examination 2021-6-21 Inspection vAsymmetry vSkin lesions vSkin changes vNipple a

14、nd areola abnormalities Palpation technique Examination of the Nipple Examination of regional lymph nodes (supraclavicular, infraclavicular, axillary) 2021-6-21 Ultrasonography is particularly suitable for the following patient groups: vLiver, gallbladder, spleen and pancrease vRetro-peritoneal vKid

15、ney and adrenal gland vBreast and thyroid Ultrasound observations vBoundaries and shape vInternal echoes vPosterior shadowing 2021-6-21 Liver and gallbladder Pancreas and spleen Kidney and Adrenal Gland Small Bowel and Colon Esophagus and Stomach Lungs and Mediastinum Musculoskeletal System Central

16、Nervous System 2021-6-21 Brain, Spine Head and Neck Breast Liver Adrenal Glands, Kidney Uterus, Ovary Prostate, Bladder Musculoskeletal System 2021-6-21 Functional and Metabolic Imaging Positron Emission Tomography (PET) Interventional Radiology Radionuclide Imaging 2021-6-21 2021-6-21 Upper Gastroi

17、ntestinal Endoscopy Endoscopic Ultrasonography Signoidoscopy, Colonoscopy Laparoscopy Endoscopic Retrograde Cholangiopancreatography Small Intestinal Endoscopy: Enteroscopy Percutaneois Endoscopic Gastrostomy Bronchoscopy Mediastinoscopy Thoracoscopy 2021-6-21 Laparoscopy Vascular Access and Special

18、ized Techniques of Drug Delivery Isolation Perfusion Intensity-Modulated Radiation Therapy 2021-6-21 Indication for FNA vWhen physical examination or mammography of the breast shows a suspicious abnormality, either a definite mass or a thickening not within the normal range, FNA is indicated. vTo di

19、stinguish between a cyst and a carcinoma vFNA biopsy or FNA cytology vUltrasound-guided FNA 2021-6-21 Indications for biopsy are generally derived from the results of physical examination or mammography. Two techniques are used for obtaining tissue suitable for histological examination, core needle

20、biopsy, and open biopsy. 2021-6-21 Core-cutting needle biopsy Stereotactically guided needle biopsy vNon-palpable lesions Open biopsy vIncisional biopsy vExcisional biopsy (excision, marking, inking, review) Open biopsy of non-palpable lesions vHooked-wire localization vSpot localization Skin biopsy

21、 (Pagets disease, inflammatory carcinoma) Biopsy of regional adenopathy 2021-6-21 Currently, Staging of cancer is determined by the TNM system of classification. vTtumor vNregional lymph nodes vMdistant metastases (Primary, Local, Regional and Distant) 2021-6-21 The goals of therapy vary with the ex

22、tent of the cancer. If the cancer is localized without evidence of spread, the goal is to eradicate the cancer and cure the patient. When the cancer is spread beyond local cure, the goal is to control the patients symptoms and to maintain maximum activity for the longest possible period of time. 202

23、1-6-21 Historical Perspective Anesthesia for Oncologic Surgery Determination of Operative Risk Roles for Surgery The Surgical Oncologist 2021-6-21 Cancer surgery has been based upon the concept that cancer begins as a local disease and spreads in an orderly fashion from the primary site to adjacent

24、tissues by direct extension to the regional lymph nodes by lymphatics and through the blood vessels. The surgical procedure was designed to remove the primary neoplasms and the usual contiguous routes of spread with aim of removing every cancer cell from the body. 2021-6-21 Only about one-third of c

25、ancer patients are cured by surgery alone, since surgical therapy, with few exceptions, is curative only in those patients in whom the disease is localized to the primary site and regional nodes. Advances in surgical techniques, anesthesia, and supportive care (blood transfusion, antibiotics, etc) h

26、ave permitted the development of more radical and extensive operative procedures. 2021-6-21 It is essential to realize that the best, and often the only, opportunity for cure is at the time of the first operation, so the operative procedure should be planned carefully. Prevention of cancer cell impl

27、antation during surgerylocal recurrence. Prevention of vascular dissemination at surgeryblood-borne metastases. “No-touch” technique, early ligation of the vascular pedicle, etc. 2021-6-21 Local resection (at least including some normal tissues surrounding) Radical local resection Radical resection

28、with en bloc excision of lymphatics Extensive surgical procedures Surgery of recurrent cancer Resection of metastases Palliative surgery 2021-6-21 肝癌肝癌肝癌肝癌 2021-6-21 Physical Consideration Biologic Considerations Tumor radiobiology Clinical Considerations 2021-6-21 Objectives of Radiotherapy vToday,

29、 its recognized that radiologists must optimize techniques and doses of radiotherapy in order to minimize the risk of local recurrence, achieve excellent cosmetic results, and avoid both short- and long-term complications. 2021-6-21 Obtain CT Scans Define Target Area Establish Irradiation Field Cons

30、truct 3D Image Create Blocks Confirm Dose Distribution 2021-6-21 Patient markings Schedule Dose Boost dose vExternal-beam radiotherapy (X-rays or electrons) vInterstitial implantation 2021-6-21 History Chemotherapy as Part of the Initial Treatment of Cancer Clinical Endpoints in Evaluating Response

31、to Chemotherapy Principles Governing the Use of Combination Chemotherapy Response to Chemotherapy Is Affected by the Biology of Tumor Growth The cell Cycle, Drug Resistance, and the P53 Tumor Suppressor Gene Pathway The concept of Dose Intensity In Vitro Drug-Response Assays 2021-6-21 The role of ch

32、emotherapy Adjuvant chemotherapy Neo-adjuvant chemotherapy Palliative chemotherapy High-dose chemotherapy 2021-6-21 Rational for adjuvant therapy vSubclinical metastases, therapy directed at the primary tumor is not helpful, vSystemic therapy after surgery, at a time when patients are clinically fre

33、e of disease but are at high risk of having residual micrometastases. vTwo types of systemic approaches are effective, chemotherapy (cytotoxic agents) and hormone therapy. 2021-6-21 Timing of Adjuvant chemotherapy Choice of chemotherapy vSingle-agent chemotherapy vCombination chemotherapy vNew cytot

34、oxic agents Dose Duration of therapy 2021-6-21 Common: Myelosuppression Alopecia NauseaPremature ovarian failure VomitingWeight gain Less Common: Systemic infections Thrombosis Neurological problems 2021-6-21 Benefits: vMetastatic breast cancer is very treatable and is one of the solid tumor most responsive to cytotoxic chemotherapy. vPatients