دانلود کتاب DiSaia and Creasman Clinical Gynecologic Oncology

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Copyright Contributors Front matter DiSaia and Creasman Clinical Gynecologic Oncology Preface Contents 1 Preinvasive disease of the cervix Key points Introduction Human papillomavirus natural history Epidemiology Human papillomavirus vaccination Screening Management of abnormal screening results Colposcopy Screening and treatment in immunocompromised women Management of abnormal screening results Managing abnormal results in young women Managing unsatisfactory cytology Cytology-negative, human papillomavirus-positive women Management of high-grade squamous intraepithelial lesion Atypical glandular cells Management of endometrial cells in older women Management of post-colposcopic results Management of women with no lesion or CIN1 at colposcopy Management of women with CIN2+ Treatment of cervical disease Management of abnormal screening results in pregnancy Future directions 2 Preinvasive disease and dystrophies of the vagina and vulva and related disorders Key points Embryology and diethylstilbestrol exposure Treatment of women exposed to diethylstilbestrol Nonneoplastic epithelial disorders of the vulva and vagina Lichen simplex chronicus Lichen sclerosus Lichen planus Pigmented lesions Diagnosis and treatment Lichen simplex chronicus Lichen sclerosus Lichen planus Vulvar intraepithelial neoplasia Terminology Progression to cancer Human papilloma virus and vaccination Diagnosis Management Excision Laser Alternative ablative techniques Non-surgical treatment Imiquimod. Cidofovir. Photodynamic therapy. Surveillance High-grade squamous intraepithelial lesion of the vagina Clinical profile Diagnosis Management 3 Invasive cervical cancer Key points General observations Anatomy Epidemiologic studies Clinical profile Clinical profile of invasive cancer Symptoms Gross appearance Routes of spread Primary group Secondary group Glandular tumors of the cervix Staging International federation of gynecology and obstetrics Positron emission tomography Surgical staging Treatment of early-stage disease Superficial carcinoma of the cervix Stage IA1 Stage IA2 Adenocarcinoma Based on current data radical treatment is not justified in patients with adenocarcinoma stage IA Radical abdominal hysterectomy with lymphadenectomy Complications Indications for postoperative adjuvant therapy Sexual function Nerve-sparing radical hysterectomy Sentinel lymph node identification Minimally invasive radical hysterectomy with lymphadenectomy Fertility-preserving surgery for early-stage tumors Cervical conization for adenocarcinoma in situ and microinvasive carcinoma Vaginal radical trachelectomy with laparoscopic lymphadenectomy Lateral ovarian transposition Treatment of locally advanced disease Radiotherapy Intensity-modulated whole pelvic radiotherapy Radium and cesium therapy Interstitial therapy Extended-field irradiation therapy Radiation and chemotherapy Neoadjuvant chemotherapy and other novel treatment approaches Suboptimal treatment situations Neuroendocrine and other uncommon tumors of the cervix Glassy cell carcinoma, carcinosarcoma, lymphoma, and melanoma Survival results and prognostic factors for early-stage and locally advanced disease Recurrent and advanced carcinoma of the cervix Management and prognosis Surgical therapy: Radical hysterectomy Pelvic exenteration Patient selection Morbidity and mortality Survival results Radiation Chemotherapy Immunotherapy for advanced cervical cancer Pembrolizumab—the first US FDA approved immunotherapy for cervical cancer Anti-PD-1 and anti-CTLA-4 combinations Adoptive T cell therapy Tissue factor as a target Anti-HER strategies 4 Endometrial hyperplasia, estrogen therapy, and the prevention of endometrial cancer Introduction Endometrial hyperplasia: Pathologic diagnostic criteria Traditional endometrial hyperplasia Endometrial intraepithelial neoplasia Endometrial intraepithelial carcinoma Clinical presentation Management decisions for endometrial intraepithelial neoplasia Management of endometrial hyperplasia without atypia Prevention of endometrial cancer Benefits and risks of menopausal hormone therapy Hot flashes Critical assessment of risk/benefit ratio of hormone therapy: The women’s health initiative data Cardiovascular disease and stroke Cardiovascular disease and cancer risk Osteoporosis Osteoporosis prevention Pharmacologic therapies and osteoporosis: Hormones Pharmacologic therapies and osteoporosis: Selective estrogen-receptor modulators Bone specific pharmacologic therapies for treatment of osteoporosis Genitourinary syndrome of menopause Special populations Early menopause Elevated risk of breast cancer Risk modification with hormone therapy: Options and opportunities Use of lower doses and different formulations Discontinuation of hormone therapy Nonhormone therapies for menopausal symptoms Menopausal hormone therapy for endometrial and breast cancer survivors Hormone therapy for endometrial cancer survivors Hormonal therapy for women with or at risk for breast cancer Hormone therapy in women with hereditary cancer syndromes BRCA1 or BRCA2 gene Lynch syndrome 5 Adenocarcinoma of the uterine corpus and sarcomas of the uterus Key points Incidence Epidemiology Diagnosis Pathology Tumor grade Prognostic factors Stage of disease: Depth of invasion, cervical involvement, adnexal involvement, and nodal metastasis Tumor grade Lymphovascular space involvement Tumor size Peritoneal cytology Molecular indices Hormone receptors. Correlation of multiple prognostic factors Treatment Surgical management of endometrial cancer Radiation therapy Chemotherapy Drug development Advanced disease Adjuvant therapy: High-risk disease Hormones Antiangiogenic therapy in endometrial cancer Immunotherapy Special circumstances Multiple malignant neoplasms Uterine serous carcinoma Uterine clear cell carcinoma Carcinosarcoma Clinical profile. Surgical management. Adjuvant therapy Management of advanced stage or recurrent disease Uterine sarcoma Classification Incidence and epidemiology Leiomyosarcoma Clinical profile Surgical management Adjuvant therapy Management of recurrent disease Endometrial stromal sarcoma Clinical profile Surgical management Adjuvant therapy Management of recurrent disease Other sarcomas Follow-up for patients with endometrial cancer 6 Invasive cancer of the vulva Key points Invasive squamous cell carcinoma Histology Clinical presentation and diagnosis Location and spread pattern Staging Molecular markers and tumor etiology Sentinel lymph node biopsy Technique of inguinofemoral lymphadenectomy Management Technique of radical vulvectomy Morbidity associated with treatment of vulvar carcinoma Survival results Tolerance of the elderly patients to therapy Recurrent disease Immunotherapy in vulvar cancer treatment Very early vulvar carcinoma Paget disease Clinical and histologic features Clinical course and management Melanoma Sarcoma Bartholin gland carcinoma Basal cell carcinoma 7 Gestational trophoblastic disease Epidemiology Hydatidiform mole Cytogenetics and pathology Presentation and symptoms Diagnosis Evacuation Risk factors for postmolar gestational trophoblastic neoplasia Postmolar surveillance Prophylactic chemotherapy after molar evacuation Coexistent molar pregnancy with a normal fetus Gestational trophoblastic neoplasia Diagnosis Abnormal human chorionic gonadotropin assays “phantom” human chorionic gonadotropin The “hook effect” Pretherapy evaluation Classification and staging Treatment of nonmetastatic and low-risk metastatic gestational trophoblastic neoplasia High-risk metastatic gestational trophoblastic neoplasia Surgery Radiation therapy Placental site trophoblastic tumor Epithelioid trophoblastic tumor Other considerations Future childbearing Coexistence of normal pregnancy and gestational trophoblastic neoplasia Transplacental fetal metastases Survivorship issues after successful treatment of gestational trophoblastic neoplasia 8 Adnexal masses Key points Adnexal masses Evaluative approach Classifying the mass OVA1 test Human epididymis protein 4 Multimodality approach Differential diagnosis Extraovarian adnexal masses Uterine masses Tubal masses Adnexal masses of nongynecologic origin Bowel Ovarian masses Functional cysts Endometriotic cysts Benign ovarian neoplasms Serous cystadenoma Mucinous cystadenoma Dermoid cyst (benign cystic teratoma) Fibroma Brenner tumor Management of adnexal masses Observation versus surgery Minimally invasive surgery for adnexal masses Special circumstances Adnexal masses in childhood Postmenopausal ovary Borderline malignant epithelial ovarian neoplasms Fertility preservation Cyst rupture or spill of tumor Prophylactic versus risk-reducing oophorectomy 9 Epithelial ovarian cancer Key points Classification Incidence, epidemiology, and etiology Familial ovarian cancer Signs and symptoms Diagnostic techniques Attempts at early detection (screening) Staging Therapeutic options for primary treatment Stages IA, IB, and IC Stages IIA and IIB Stage III Stage IV Surgery Maximal surgical effort Role of minimally invasive surgery Neoadjuvant chemotherapy and interval cytoreductive surgery Systemic therapy/chemotherapy Conventional (dose-intense platinum chemotherapy) Dose-dense paclitaxel Intraperitoneal chemotherapy Bevacizumab Treatment for rare epithelial histologies Frontline maintenance therapy Other considerations Extraovarian peritoneal serous papillary carcinoma Small cell carcinoma of the ovary Borderline epithelial neoplasms of the ovary Surveillance and follow-up techniques Use of CA 125 levels and other tumor markers Radiographic imaging Treatment for recurrent disease and targeted therapies Platinum-sensitive disease Platinum-resistant disease Targeted therapy Immunotherapy Surgery for recurrent disease Radiation Palliative/end of life support Conclusions on management Current areas of research 10 Germ cell, stromal, and other ovarian tumors Key points Germ cell tumors Classification Clinical profile Staging Treatment options Surveillance for stage I tumors Second-look laparotomy Radiation therapy Chemotherapy Neoadjuvant chemotherapy Recurrences in germ cell cancer Treatment toxicity Dysgerminoma Endodermal sinus tumor (yolk sac tumor) Embryonal carcinoma Polyembryoma Choriocarcinoma Mixed germ cell tumors Teratoma Mature cystic teratoma Mature solid teratoma Immature teratoma Monodermal or highly specialized teratomas Struma ovarii. Carcinoid tumors. Tumors of germ cell and sex cord derivation Gonadoblastoma Mixed germ cell–sex cord stromal tumors Tumors derived from special gonadal stroma Classification, clinical profile, and staging Treatment Granulosa–stromal cell tumors Thecomas Fibromas and sclerosing stromal cell tumors Sertoli-leydig cell tumors Sex cord tumor with annular tubules Gynandroblastoma Steroid cell neoplasms Tumors derived from nonspecific mesenchyme Small cell carcinoma of the ovary, hypercalcemic type Malignant lymphoma Metastatic tumors to the ovary Malignant ovarian tumors in children 11 Breast diseases Key points Introduction Anatomy of the breast Embryology and development of the breast Pregnancy and breast feeding Benign breast conditions Fibrocystic change Proliferative changes Complex sclerosing lesions Fibroadenoma Phyllodes tumor Adenoma Superficial thrombophlebitis Mastitis Duct ectasia Fat necrosis Nipple discharge History and physical examination Breast imaging Mammography Screening interval Breast imaging reporting and data system Diagnostic mammography Mammographic lesions Microcalcifications Digital mammography Breast ultrasound and magnetic resonance imaging Diagnostic evaluation Palpable mass Fine-needle aspiration or biopsy Image-guided percutaneous breast biopsy Ultrasound-guided biopsy Tissue-acquisition devices Excisional biopsy Surgical excision/breast biopsy Epidemiology of breast cancer Risk factors and assessment Age Family history and hereditary risk Personal history Reproductive history Exogenous hormone use Prior exposure to radiation therapy Other factors Relative risk and risk-assessment models Natural history Pathology Ductal carcinoma in situ Paget’s disease Lobular carcinoma in situ Invasive ductal carcinoma Infiltrating lobular carcinoma Inflammatory carcinoma Metastases from extramammary tumors Biologic markers and prognostic factors Axillary lymph node status Tumor size Histologic grade Hormone receptors HER2 Ki-67 Molecular profiling Staging of breast cancer using the tumor–node–metastasis system Treatment of breast cancer Surgery Mastectomy Breast-conservation therapy Patient selection Management of the axilla Sentinel lymph node biopsy Adjuvant therapy Neoadjuvant chemotherapy Estrogen receptor-positive breast cancer Gene expression assays HER2 positive breast cancer Triple negative breast cancer Endocrine therapy Ovarian ablation Tamoxifen Aromatase inhibitors Radiation therapy Breast reconstruction Special issues Breast cancer in the elderly woman Pregnancy and fertility BRCA1 and BRCA2 Pathologic features and stage Treatment Chemoprevention Metastatic disease Conclusions 12 Cancer in pregnancy Key points Background and epidemiology of cancer Report from the european society of gynecological oncology cancer in pregnancy task force The more common solid tumors Cervical cancer Human papillomavirus in pregnancy Evaluation of cervical cytology in pregnancy The performance of colposcopy in pregnancy The natural history of cervical intraepithelial neoplasia in pregnancy Conization and related procedures in pregnancy Management of cervical intraepithelial neoplasia in pregnancy Management of squamous cell abnormalities Management of glandular cell abnormalities Intrapartum hysterectomy Invasive cervical cancer Microinvasive disease Cesarean–radical hysterectomy with pelvic lymphadenectomies Radical trachelectomy with lymphadenectomy Whole-pelvis radiotherapy with intracavitary brachytherapy Episiotomy site recurrence Planned delay of therapy Neoadjuvant chemotherapy in pregnancy Prognosis for patients with cervical cancer in pregnancy Obstetric outcomes Ovarian cancer Asymptomatic adnexal masses Surgical management of the ovarian mass Robotic-assisted laparoscopic management of adnexal masses during pregnancy Ovarian masses specific to pregnancy Histologic types of ovarian tumors Borderline ovarian tumors Frankly malignant ovarian tumors Malignant germ cell tumors in pregnancy Dysgerminoma in pregnancy Sex cord–stromal tumors in pregnancy Chemotherapy for nonepithelial ovarian cancer during pregnancy Epithelial ovarian cancer in pregnancy Chemotherapy for epithelial ovarian cancer during pregnancy Targeted (biologic) therapy for ovarian cancer in pregnancy Vascular endothelial growth factor inhibitors. PARP inhibitors. Other types of malignant ovarian tumors Summary of the adnexal mass and ovarian cancer in pregnancy Breast cancer Prognosis Presentation Evaluation Surgical management Sentinel lymph node identification Breast reconstruction Adjuvant therapy Neoadjuvant and adjuvant chemotherapy for pregnancy-associated breast cancer Chemotherapy for metastatic breast cancer HER2/neu–targeted agents in pregnancy Hormonal treatments for pregnancy-associated breast cancer Prognosis of pregnancy-associated breast cancer Lactation Hormonal considerations: Pregnancy preceding breast cancer Protective effect of human chorionic gonadotropin. Recent antecedent pregnancy. Breastfeeding. Hormonal considerations: Pregnancy coincident with breast cancer Estrogen-receptor and progesterone-receptor status Pregnancy termination Tamoxifen Hormonal considerations: Pregnancy after breast cancer Prophylactic oophorectomy Survival among patients with pregnancy-associated breast cancer Evaluation and therapeutic modalities Anesthesia and surgery in pregnant patients Anesthesia Surgery Laparotomy Laparoscopy Diagnostic and therapeutic radiation in pregnancy Radiobiology Radiation-induced anomalies Diagnostic radiology Ionizing radiation Nonionizing radiation Radionuclides Radiation therapy Radiation-induced carcinogenesis Genetic damage and infertility Chemotherapy Teratology and embryology Transplacental studies Classes of antineoplastic agents Antimetabolites. Alkylators. Anthracycline and antitumor antibiotics Plant alkaloids Taxanes Platinum analogs Targeted therapeutic pathways and placental development. Pharmacokinetics, sublethal fetal effects, and maternal risks Estimating the stillbirth rate Occupational exposure Recommendations on the use of chemotherapy during pregnancy Timing of delivery Breastfeeding Long-term neonatal follow-up Supportive therapy Serum tumor markers in pregnancy Obstetric considerations and antepartum management Reproductive options and counseling. Periviability. Anticoagulation. Antepartum monitoring and surveillance. Antenatal corticosteroids. Peripartum considerations. Postpartum care. Highlighted maternal-fetal medicine points Hematologic malignancies Leukemia Leukemia in pregnancy Chemotherapy for acute leukemia in pregnancy Acute myelogenous leukemia Acute lymphoblastic leukemia Acute promyelocytic leukemia Management of chronic leukemia Chronic myelocytic leukemia Hairy cell leukemia, multiple myeloma, and chronic lymphocytic leukemia Hodgkin disease Hodgkin disease in pregnancy Management of Hodgkin disease in pregnancy Non-Hodgkin lymphoma Non-Hodgkin lymphoma in pregnancy Other tumors Melanoma Staging of melanoma Melanoma in pregnancy Historical series of melanoma in pregnancy Contemporary studies of melanoma in pregnancy Management of melanoma in pregnancy Melanoma metastatic to the products of conception Thyroid cancer Thyroid cancer in pregnancy Undifferentiated lesions Prognosis among pregnant women with thyroid cancer Rare gynecologic malignancies in pregnancy Vulvar cancer Historical series of vulvar cancer in pregnancy. Management of vulvar cancer in pregnancy. Primary invasive vaginal tumors Endometrial cancer Fallopian tube cancer Trophoblastic tumors of the fallopian tube: “ectopic” pregnancy Placental and fetal tumors Complete hydatidiform mole with coexistent fetus Placental and fetal metastases Primary fetal tumors 13 Complications of disease and therapy Key points Disease–oriented complications Hemorrhage Urinary tract complications Ureteral obstruction Urinary tract fistulas Gastrointestinal complications Gastrointestinal obstruction Gastrointestinal fistulas Biliary obstruction Treatment-related complications Surgical Intraoperative and postoperative hemorrhage Intraoperative management of vascular complications. Hypogastric (internal iliac) artery ligation. Intraoperative and postoperative genitourinary tract injuries Intraoperative genitourinary injuries. Postoperative genitourinary injuries. Bladder dysfunction after radical surgery Intraoperative and postoperative gastrointestinal tract injuries Venous thromboembolic complications Risk factors Prophylactic methods Pharmacologic venous thromboembolism prophylaxis. Oral agents. Mechanical methods Extended postoperative prophylaxis Management of deep vein thrombosis and pulmonary embolism Diagnosis of deep vein thrombosis. Diagnosis of pulmonary embolism. Treatment of deep vein thrombosis. Low-molecular-weight heparin. Unfractionated heparin. Doacs and warfarin. Long-term anticoagulation. Inferior vena cava filter. Pulmonary embolism. Superior vena cava syndrome. Lymphedema Lymphocysts Postoperative infections Urinary tract infections. Pulmonary infections. Wound infections. Intraabdominal and pelvic abscesses. Necrotizing fasciitis. Special populations Obesity Incidence and definition. Postoperative complications and management. Elderly patients. Radiation therapy Gastrointestinal complications Acute complications. Chronic complications. Urologic complications Sexual function and vaginal stenosis 14 Basic principles of chemotherapy and other systemic therapies Key points Historical overview General principles Cell cycle control and growth kinetics Dynamics of chemotherapy Pharmacologic principles Drug interactions Drug resistance Calculation of dosage Jelliffe method Cockroft–Gault method Calvert formula Categories of drugs in current use (Table 14.7) Alkylating agents Antimetabolites Antitumor antibiotics Agents derived from plants Hormonal agents Targeted therapies and immunotherapy Drug toxicity Hematologic toxicity Growth factor therapy Granulocyte-stimulating therapy. Erythrocyte-stimulating therapy. Platelet-stimulating therapy. Gastrointestinal toxicity Skin reactions Hypersensitivity Hepatic toxicity Pulmonary toxicity Cardiac toxicity Renal toxicity Genitourinary toxicity Neurologic toxicity Gonadal dysfunction Immune-related adverse events Supportive care Evaluation of new agents Phase I Phase II Phase III Phase IV 15 Targeted therapy and molecular genetics Key points Targeted therapy Foundation of targeted therapy Targeted agents Angiogenesis Vascular endothelial growth factors and vascular endothelial growth factor receptors Agents targeting the vascular endothelial growth factor pathway Bevacizumab Ovarian cancer. Uterine cancer. Cervical cancer. Vascular endothelial growth factor-trap (aflibercept) Agents targeting vascular endothelial growth factor receptors AZD2171 (cediranib) Agents targeting multiple vascular endothelial growth factor–related molecules Sunitinib Pazopanib Nintedanib Lenvatinib Vascular disrupting agents Vadimezan (ASA404/DMXAA) Fosbretabulin (combretastatin A4); ombrabulin (AVE8062) Ofranergene obadenovec (VB-111) Phosphatidylinositol-3-kinase/AKT pathway Agents targeting mammalian target of rapamycin Temsirolimus (CC1-779) Everolimus (RAD001) Ridaforolimus (AP23573; MK-8669) Agents targeting AKT Agents targeting PI3K Combination agents Ras/Raf pathway Agents targeting MEK Poly (ADP-ribose) polymerase pathway Olaparib Rucaparib Niraparib Veliparib Epidermal growth factor receptor pathway Small molecule inhibitors targeting epidermal growth factor receptor Gefitinib Erlotinib Monoclonal antibodies targeting epidermal growth factor receptor Cetuximab Trastuzumab Pertuzumab Seribantumab Combination agents Lapatinib Multipathway targeted agents Sorafenib Vandetanib Imatinib Dasatinib Cabozantinib (XL-184) Other targets of interest Angiopoietin (Ang)/Tie-2 Aurora kinase Delta-like 4 (DII4)/Notch Folate receptor α Antimesothelin antibodies Tissue factor Histone acetyltransferases and histone deacetylases Platelet-derived growth factor P53 Immune therapy Unique toxicities of targeted therapy Hypertension Reverse protein leukoencephalopathy Cardiotoxicity Renal toxicity Thromboembolic events Gastrointestinal perforation and fistula Cutaneous complications Metabolic abnormalities Special considerations for targeted therapies Conclusions Acknowledgments 16 Molecular hallmarks of cancer Key points Biology of gynecologic cancers Molecular changes in gynecologic malignancies Cell cycle Agents Mechanism of targeted agents Targets Angiogenesis Vascular endothelial growth factors and receptors Poly-adenosine diphosphate-ribose polymerase pathway Olaparib Rucaparib Niraparib Veliparib The immunologic cascade Immune checkpoint inhibitors PD-1/PD-L1 pathway Pembrolizumab Nivolumab Other PD-1/PD-L1 inhibitors Cytotoxic T-lymphocyte-associated antigen 4 inhibitors Therapeutic vaccines Antibody drug conjugates Ras/Raf/mitogen-activated protein kinase pathway Agents targeting mitogen-activated protein kinase Epidermal growth factor receptor pathway Epigenetic considerations Histone acetyltransferases and deacetylases Special considerations with targeted therapies Hypertension Cardiotoxicity Gastrointestinal toxicities Dermatologic events Endocrine and metabolic abnormalities Secondary malignancies Assessing therapy response Conclusions 17 Immunotherapy in gynecologic malignancies Cytokines Interleukin-2 Interleukin-12 Interferons Monoclonal antibodies Oregovomab Human Milk Fat Globule 1 Catumaxomab Farletuzumab (MORab003) Antibody-drug conjugate Mirvetuximab soravtansine (IMGN853) Clinical use of antibody drug conjugates Ovarian cancer Cervical cancer Immune checkpoint inhibitors Anti-cytotoxic T lymphocyte-associated protein 4 antibodies Ipilimumab Tremelimumab Zalifrelimab Clinical use of anti-CTLA-4 antibodies Ovarian cancer, cervical cancer Anti-programmed cell death receptor-1 antibodies Pembrolizumab (MK-3475) Nivolumab Dostarlimab Balstilimab Cemiplimab Anti-PD-L1 (programmed cell death receptor ligand-1) antibodies Durvalumab Avelumab Atezolizumab Clinical use of anti-PD-(L)1 antibodies Endometrial cancer Ovarian cancer Cervical cancer Gestational trophoblastic neoplasia Clinical use of combined immune checkpoint inhibition Endometrial cancer Ovarian cancer Cervical cancer Resistance mechanisms to immune checkpoint inhibition Therapeutic cancer vaccines Peptide/protein-based vaccines Ovarian cancer New york esophageal squamous cell carcinoma 1 Ovarian cancer. DPX-survivac Ovarian cancer. Cell-based vaccines Ovarian cancer DNA/RNA-based vaccines Recombinant vaccinia and fowlpox vectors Ovarian cancer. Engineered listeria monocytogenes Cervical cancer, ovarian cancer. Glycan-based vaccines Lewis(y) Adoptive cell therapy Tumor-infiltrating lymphocytes therapy Ovarian cancer Cervical cancer Engineered T cell receptor therapy Ovarian cancer Engineered T cell chimeric antigen receptor therapy Ovarian cancer Natural killer cell therapy Immune-related adverse events Therapy of immune-related adverse events Special patient populations Obstacles to immunotherapy Summary 18 Genes and cancer: Genetic counselling and clinical management Key points Introduction Genetic alterations in cancer Mechanisms of human gene mutation Single base pair substitutions and point mutations Larger deletions Insertions Duplications Inversions Translocations Cancer epigenetics Genomic imprinting and cancer Genetic alterations that cause cancer Oncogenes Tumor suppressor genes Apoptosis Mismatch repair defects Telomerase Hereditary cancer risk assessment: Genetic counseling and genetic testing Clinically relevant hereditary syndromes Pre-test counseling Ordering genetic tests Post-test counseling Hereditary breast and ovarian cancer (BRCA1 and BRCA2; other DNA repair pathway genes) Management guidelines for hereditary breast and ovarian cancer (BRCA1 and BRCA2) Lynch syndrome (hereditary nonpolyposis colon cancer) Genetic testing for lynch syndrome Management guidelines for lynch syndrome Less common inherited cancer syndromes relevant to gynecologic oncology Peutz-jeghers syndrome Management guidelines for Peutz-Jeghers syndrome. Cowden syndrome Li-fraumeni syndrome Moderate risk and preliminary evidence genes Genetic counseling and genetic testing for hereditary cancers Referral of gynecologic cancer patients for hereditary cancer risk assessment Ovarian cancer Timing of referral for patients with ovarian cancer Endometrial cancer Referral of the patient for genetic counseling based on personal history of breast cancer or family history of cancer Genetic testing General guidelines for genetic testing for hereditary cancer risk Informed consent Ordering genetic testing Interpreting the test results Legal aspects of genetic testing Long-term contact for patients and families with hereditary risk for cancer DNA banking Conclusion Glossary A C D E G H I L M N O P R T U V W 19 Palliative care and quality of life Key points Evolution of palliative care Quality of life in gynecologic cancers Quality of life in ovarian cancer Quality of life in cervical cancer Quality of life in endometrial cancer Management of common physical symptoms Fatigue Pain Nausea and vomiting Diarrhea and constipation Cachexia and malnutrition Psychosocial and spiritual needs of patients and families Strategies for breaking bad news and preserving hope Management of psychosocial and spiritual distress Quality of life issues in advanced and recurrent ovarian cancer Pleural effusions Small bowel obstruction Ascites Role of palliative surgical procedures Quality of life issues in advanced and recurrent uterine and cervical cancer Ureteral obstruction Fistula Sexual dysfunction Anxiety and depression End-of-life decision making Patient benefit Patient self-determination Legal developments that have a bearing on end-of-life decision making Surrogate decision making Futility Hospice 20 Role of minimally invasive surgery in gynecologic malignancies Key points Laparoscopic surgery in gynecologic oncology Laparoscopic surgical staging of gynecologic malignancies Robotic surgery in gynecologic malignancies Length of stay Minimally invasive surgery learning curve Minimally invasive surgical technique Positioning of the patient Port sites and setup Surgery in the overweight and underweight patient Surgical procedure and technique Applications of minimally invasive surgery in gynecologic oncology Cervical cancer Early-stage cervical cancer: Radical hysterectomy Early-stage cervical cancer: Fertility-sparing surgery Advanced-stage cervical cancer: Surgical staging Endometrial cancer Laparoscopy Robotics Single-site surgery Minimally invasive sentinel lymph node assessment Removal of a large uterus Uterine manipulation for minimally invasive surgery Adnexal mass Minimally invasive surgery management Ovarian cancer Diagnosis of ovarian cancer Ovarian cyst rupture Early-stage ovarian cancer Advanced ovarian cancer Complications of laparoscopic surgery Port-site recurrences Conclusions 21 Epidemiology of commonly used statistical terms, and analysis of clinical studies Key points Epidemiology Evidence-based medicine Measures in epidemiology Analysis of clinical trials Graphical displays of complex statistical data Forest plot Swimmers plot Waterfall plot Types of clinical trials Evaluation of clinical trials Placebo treatment groups Controls used in clinical trials Studies of therapy Master protocols Blinding When to stop a clinical trial 22 Basic principles in gynecologic radiotherapy Key points Introduction to electromagnetic radiation Radiation units Radiation physics Energy deposition Sources of radiation Photon interactions Radioactive decay Inverse square law Depth dose characteristics of radiation Radiobiology Structural changes Radiosensitivity Radiobiology of ablative radiotherapy Radiosensitizers, hypoxic cell sensitizers, and radioprotectors Genetic effects Fetal effects Principles of clinical radiation therapy External-beam radiation (teletherapy) Local radiation (brachytherapy) Normal tissue tolerance Pelvic organ tolerance Long-term effects New radiation modalities Protons Electrons Fast neutrons Negative pi mesons and other heavy ions New radiation delivery technology Intraoperative radiation Hyperthermia Three-dimensional conformal radiation therapy Intensity-modulated radiation therapy Stereotactic radiotherapy Immunotherapy and radiation therapy Glossary A B D E G H I K L M O P R S X APPENDIX A Staging APPENDIX B Modified from common terminology criteria for adverse events (Common Terminology Criteria for Adverse Events) Quick reference Components and organization System organ class CTCAE terms Grades APPENDIX C Blood component therapy APPENDIX D Suggested recommendations for routine cancer screening Cervical cancer Breast cancer Endometrial cancer Ovarian cancer Colorectal cancer Lung cancer Skin cancer APPENDIX E Normal nutrition Malnutrition and malignancy Diagnosis of malnutrition Nutritional supplementation Additional therapies Index A B C D E F G H I J K L M N O P Q R S T U V W Y Z