《外科学总论》课件：CANCER

1、2020/9/15,CANCER Principles & Practice of Oncology,Lisong Teng MD, PhD The Department of Oncological Surgery 1st Affiliated Hospital of ZJUMC,2020/9/15,Neoplasms (Tumor, Mass),An altered cell population characterized by an excessive, nonuseful proliferation of cells that have become unresponsive to

2、normal control mechanisms and to the organizing influences of adjacent tissues.,2020/9/15,Classification of Neoplasms,Benign tumor Malignant tumor (Cancer) Carcinoma Sarcoma Bordering tumor,2020/9/15,Essentials of Modern Oncologic Science,Essentials of Moledular Biology: Genomics and Cancer Essentia

3、ls of Signal Transduction Essentials of Immunology,2020/9/15,Principles of Oncology,Molecular Biology of Cancer: Oncogenes Identification of Oncogenes and Tumor Suppressor Genes Function of Oncogenes and Tumor Suppressor Genes,2020/9/15,Tumor Related Genes Oncogene, proto-oncogene ras, myc, erb2, sr

4、c, c-fos, c-jun etc. Tumor suppress gene RB, p53, APC, WT1 etc. DNA damage and repair related gene hMSH2, hMLH1, PMS1, PMS2,2020/9/15,Function of Oncogenes and Tumor Suppressor Genes,Signal Transduction (ras) Extracellular Growth Factors (Sis) Receptor Tyrosine Kinases (RET) Nuclear Proteins and Tra

5、nscription factors (jun, BRCA1,2, myc, myb) Cell Cycle/DNA Damage Response (p53, RB, hMSH, MDM-2),2020/9/15,Molecular Markers in Cancer Diagnosis,Chromosomal rearrangements DNA rearrangements Small Mutation: K-ras, p53, APC Tissue-specific transcripts Viral genomes,2020/9/15,2020/9/15,高通量分析技术Tissue

6、Array,2020/9/15,2020/9/15,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,高通量分析技术基因芯片(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,2020/9/15,Telomerase, Cell Aging and Cancer,Time,Telomere Length,Critical Telomere Length,Normal Cells,Stem & Tumor Cells,2020/9/15,Moledular Biolog

7、y of Cancer,Cytogenetics The Cell Cycle Apoptosis Angiogenesis Invasion and Metastasis,2020/9/15,2020/9/15,2020/9/15,2020/9/15,组织细胞数量细胞增殖细胞死亡 Tissue Cell No. = Cell Proliferation - Cell Death,癌基因和抗癌基因 Oncogenes and Tumor Suppressor Genes,凋亡和抗凋亡基因 Apoptosis Gene and Anti-apoptosis Gene,2020/9/15,正 常

8、粘 膜,I,癌,转 移,APC,K-ras,DCC,P53,nm23,?其它,甲基化,5q 突变 . 缺失,12p 突变,18q 突变 ? 缺失,17p 突变 . 缺失,II,III,IV,Adenoma,MCC hMSH2 hMLH1 hPMS1 hPMS2,ACF,COX-2,SNC6，SNC73,SNC19，maspin，osteo,2020/9/15,2020/9/15,Etiology of Cancer,Viruses (DNA and RNA Viruses) Chemical Factors Physical Factors Hormonal Factors Cancer Ge

9、netics (Hereditary factors),2020/9/15,肿 瘤 发 生 机 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）,2020/9/15,Cancer Genetics,Cancer as a Genetic Disease Mechanisms of Cancer Predisposition Clinical Characteristics of Cancer Families Multisystem Genetic

10、 Syndromes With a High Risk of Cancer Nonsyndromic Hereditary Cancer,2020/9/15,Epidemiology of Cancer,Human Carcinogenesis: The Nature of the Evidence Cancer Epidemiology by Site An Overview of Cancer Causes,2020/9/15,Cancer Prevention:,Preventing Tobacco-Related Cancers Diet and Chemopreventive Age

11、nts: Fat: Breast Cancer, Colon Cancer, Prostate Cancer and other Cancer Dietary Fibers Retinoids, Carotenoids, and Micronutrients Naturally Occurring Dietary Anticarcinogens Dietary Carcinogens Aspirin and Other Nonsteroidal Antiinflammatory Drugs and the Risk of Cancer Development Physical Activity

12、 and Body Weight Role of Surgery in Cancer Prevention,2020/9/15,Cancer Screening,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,2020/9/15,Path

13、ology of Neoplasms,Carcinogenesis and Tumorigenesis Tumor cell differentiation Growth pattern Growth rate (speed) Metastasis Direct Extension Lymphatic Spread Vascular Spread Spread through Serous Cavities,2020/9/15,Cancer Diagnosis: Molecular Pathology,Immunohistochemistry DNA Content Diagnostic Mo

14、lecular Genetics Techniques in the Molecular Genetic Diagnosis of Cancer Molecular Markers in Cancer Diagnosis Small Mutations Future Expectations,2020/9/15,Clinical Manifestations,Cancers seven warning signals Change in bowel or bladder habits A sore that does not heal Unusual bleeding or discharge

15、 Thickening or lump in breast or elsewhere Indigestion or difficulty in swallowing Obvious change in wart or mole Nagging cough or hoarseness,2020/9/15,Local manifestations of cancer,Mass Pain Ulcer Bleeding Obstruction Metastatic Manifestations,2020/9/15,2020/9/15,2020/9/15,2020/9/15,Systemic Manif

16、estation of cancer,Non-specific: Anemia Low fever Weight loss Inertia Anorexia-cachexia and others,2020/9/15,2020/9/15,Diagnosis of cancer should proceed in on orderly fashion: Careful history (Details of risk factors including family history and current medication should be noted in the patients re

17、cords) Thorough physical examination Laboratory examination Imaging examination,Cancer Diagnosis,2020/9/15,Clinical Breast Examination,Inspection Asymmetry Skin lesions Skin changes Nipple and areola abnormalities Palpation technique Examination of the Nipple Examination of regional lymph nodes (sup

18、raclavicular, infraclavicular, axillary),2020/9/15,Cancer Diagnosis: ImagingUltrasonography,Ultrasonography is particularly suitable for the following patient groups: Liver, gallbladder, spleen and pancrease Retro-peritoneal Kidney and adrenal gland Breast and thyroid Ultrasound observations Boundar

19、ies and shape Internal echoes Posterior shadowing,2020/9/15,Cancer Diagnosis: ImagingComputed Tomography,Liver and gallbladder Pancreas and spleen Kidney and Adrenal Gland Small Bowel and Colon Esophagus and Stomach Lungs and Mediastinum Musculoskeletal System Central Nervous System,2020/9/15,Cancer

20、 Diagnosis: ImagingMagnetic Resonance Imaging,Brain, Spine Head and Neck Breast Liver Adrenal Glands, Kidney Uterus, Ovary Prostate, Bladder Musculoskeletal System,2020/9/15,Cancer Diagnosis: Other Imagings,Functional and Metabolic ImagingPositron Emission Tomography (PET) Interventional Radiology R

21、adionuclide Imaging,2020/9/15,2020/9/15,Cancer Diagnosis: Endoscopy,Upper Gastrointestinal Endoscopy Endoscopic Ultrasonography Signoidoscopy, Colonoscopy Laparoscopy Endoscopic Retrograde Cholangiopancreatography Small Intestinal Endoscopy: Enteroscopy Percutaneois Endoscopic Gastrostomy Bronchosco

22、py Mediastinoscopy Thoracoscopy,2020/9/15,Specialized Techniques in Cancer Managemnt,Laparoscopy Vascular Access and Specialized Techniques of Drug Delivery Isolation Perfusion Intensity-Modulated Radiation Therapy,2020/9/15,Fine Needle Aspiration,Indication for FNA When physical examination or mamm

23、ography of the breast shows a suspicious abnormality, either a definite mass or a thickening not within the normal range, FNA is indicated. To distinguish between a cyst and a carcinoma FNA biopsy or FNA cytology Ultrasound-guided FNA,2020/9/15,Biopsy,Indications for biopsy are generally derived fro

24、m the results of physical examination or mammography. Two techniques are used for obtaining tissue suitable for histological examination, core needle biopsy, and open biopsy.,2020/9/15,Core-cutting needle biopsy Stereotactically guided needle biopsy Non-palpable lesions Open biopsy Incisional biopsy

25、 Excisional biopsy (excision, marking, inking, review) Open biopsy of non-palpable lesions Hooked-wire localization Spot localization Skin biopsy (Pagets disease, inflammatory carcinoma) Biopsy of regional adenopathy,2020/9/15,Staging,Currently, Staging of cancer is determined by the TNM system of c

26、lassification. Ttumor Nregional lymph nodes Mdistant metastases (Primary, Local, Regional and Distant),2020/9/15,Principles of Cancer Management: Goals of therapyCure or Palliation,The goals of therapy vary with the extent of the cancer. If the cancer is localized without evidence of spread, the goa

27、l 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.,2020/9/15,Principles of Cancer Management: Surgical Oncology,Historical Perspective A

28、nesthesia for Oncologic Surgery Determination of Operative Risk Roles for Surgery The Surgical Oncologist,2020/9/15,Surgical Therapy,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 tissues by dir

29、ect 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.,2020/9/15,Surgical Therapy,Only about one-third o

30、f cancer 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

31、) have permitted the development of more radical and extensive operative procedures.,2020/9/15,Surgical Therapy,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

32、 of cancer cell implantation during surgerylocal recurrence. Prevention of vascular dissemination at surgeryblood-borne metastases. “No-touch” technique, early ligation of the vascular pedicle, etc.,2020/9/15,Surgical Therapy: Types of Cancer Operations,Local resection (at least including some norma

33、l tissues surrounding) Radical local resection Radical resection with en bloc excision of lymphatics Extensive surgical procedures Surgery of recurrent cancer Resection of metastases Palliative surgery,2020/9/15,2020/9/15,Principles of Cancer Management: Radiation Therapy,Physical Consideration Biol

34、ogic Considerations Tumor radiobiology Clinical Considerations,2020/9/15,Radiotherapy,Objectives of Radiotherapy Today, 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

35、 both short- and long-term complications.,2020/9/15,Treatment Planning,Obtain CT Scans Define Target Area Establish Irradiation Field Construct 3D Image Create Blocks Confirm Dose Distribution,2020/9/15,The technique of radiotherapy,Patient markings Schedule Dose Boost dose External-beam radiotherap

36、y (X-rays or electrons) Interstitial implantation,2020/9/15,Chemotherapy,History Chemotherapy as Part of the Initial Treatment of Cancer Clinical Endpoints in Evaluating Response to Chemotherapy Principles Governing the Use of Combination Chemotherapy Response to Chemotherapy Is Affected by the Biol

37、ogy 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,2020/9/15,Types of Chemotherapy,The role of chemotherapy Adjuvant chemotherapy Neo-adjuvant chemotherapy Palliative chemotherapy High-dose chemot

38、herapy,2020/9/15,Adjuvant chemotherapy,Rational for adjuvant therapy Subclinical metastases, therapy directed at the primary tumor is not helpful, Systemic therapy after surgery, at a time when patients are clinically free of disease but are at high risk of having residual micrometastases. Two types

39、 of systemic approaches are effective, chemotherapy (cytotoxic agents) and hormone therapy.,2020/9/15,Adjuvant chemotherapy,Timing of Adjuvant chemotherapy Choice of chemotherapy Single-agent chemotherapy Combination chemotherapy New cytotoxic agents Dose Duration of therapy,2020/9/15,Toxicity of ad

40、juvant chemotherapy,Common: Myelosuppression Alopecia NauseaPremature ovarian failure VomitingWeight gain Less Common: Systemic infections Thrombosis Neurological problems,2020/9/15,Palliative chemotherapy,Benefits: Metastatic breast cancer is very treatable and is one of the solid tumor most responsive to cytotox