Male Reproductive System Overview PDF

Resume pt 2 Male Reproductive System Overview 1. Introduction The male reproductive system is specialized for the production, storage, and delivery of sperm and the secretion of male sex hormones, primarily testosterone....

Resume pt 2 Male Reproductive System Overview 1. Introduction The male reproductive system is specialized for the production, storage, and delivery of sperm and the secretion of male sex hormones, primarily testosterone. 2. Anatomy and Components 2.1 Testis 1. Location and Setting: Located in the scrotum, outside the abdominal cavity, to maintain optimal temperature for spermatogenesis. Encased in the tunica vaginalis and supported by the scrotal ligament. 2. Macroscopic Features: Divided into lobules containing seminiferous tubules, where sperm production occurs. Rete testis and mediastinum are key structures for sperm transport. Resume pt 2 1  3. Microscopic Features: Seminiferous tubules: Site of spermatogenesis. Interstitial (Leydig) cells: Produce testosterone. Sertoli cells: Provide nourishment and structural support for developing sperm. 4. Blood Supply: Testicular arteries and veins form the pampiniform plexus, which aids in temperature regulation. 2.2 Spermatic Pathway Resume pt 2 2  1. Epididymis: Long coiled duct where sperm mature and gain motility. 2. Ductus (Vas) Deferens: Transports sperm from the epididymis to the ejaculatory ducts. 3. Ejaculatory Duct: Formed by the union of the vas deferens and seminal vesicle duct, it empties into the urethra. 2.3 Accessory Glands 1. Prostate: Produces prostatic fluid, which contributes to semen volume and enhances sperm motility. 2. Seminal Vesicles: Secrete a fructose-rich fluid to provide energy for sperm. 3. Bulbourethral Glands: Produce a mucus-like secretion to lubricate the urethra and neutralize acidity. 2.4 External Genitalia 1. Penis: Comprised of erectile bodies: Corpus cavernosum (paired). Corpus spongiosum, which surrounds the urethra. Blood supply involves the superficial and deep arterial systems, drained by the venous system. 2. Scrotum: Protective sac that houses the testes and regulates temperature. 3. Functions 1. Spermatogenesis: Resume pt 2 3  The production of sperm in the seminiferous tubules. Involves stages: spermatogonia → primary spermatocytes → secondary spermatocytes → spermatids → spermatozoa. 2. Hormone Production: Testosterone is secreted by Leydig cells and is critical for: Development of secondary sexual characteristics. Maintenance of libido and spermatogenesis. 3. Semen Production: Contributions from the prostate, seminal vesicles, and bulbourethral glands ensure optimal sperm transport and survival. 4. Clinical Correlation 1. Disorders of the Testis: Cryptorchidism: Failure of the testes to descend, increasing infertility risk. Testicular torsion: Twisting of the spermatic cord, causing ischemia. Testicular cancer: Often presents as a painless lump. 2. Prostate Disorders: Benign Prostatic Hyperplasia (BPH): Enlarged prostate causing urinary symptoms. Prostate cancer: Common malignancy in older men. 3. Infertility: Can result from abnormal sperm production, hormone imbalances, or obstructed pathways. Summary Table Structure Function Key Features Sperm production, testosterone Seminiferous tubules, Leydig Testis secretion cells, Sertoli cells Epididymis Sperm maturation and storage Coiled duct posterior to the Resume pt 2 4  testis Sperm transport to ejaculatory Vas Deferens Thick muscular walls duct Secretes prostatic fluid to Prostate Surrounds the urethra enhance motility Provides energy-rich fructose Seminal Vesicles Located posterior to the bladder fluid for sperm Bulbourethral Secretes pre-ejaculate for Situated inferior to the prostate Glands lubrication and neutralization Facilitates copulation and semen Erectile tissue, arterial and Penis delivery venous systems for erection This comprehensive overview covers the male reproductive system's anatomy, physiology, and clinical relevance, providing a thorough foundation for understanding its function and associated disorders. Child Development Overview of Child Development Child development refers to the progression of physical, cognitive, emotional, and social changes that occur from birth through adolescence. It is influenced by genetic, environmental, and cultural factors, and proper assessment tools help monitor a child’s growth to ensure they are meeting developmental milestones. Key Domains of Child Development 1. Physical Development: Growth in height, weight, and motor skills. Milestones include rolling over, sitting, walking, and fine motor tasks like grasping. 2. Cognitive Development: Development of thinking, problem-solving, and understanding. Includes memory, learning, and language acquisition. 3. Social-Emotional Development: Resume pt 2 5  Ability to form relationships, self-regulate emotions, and interact with others. Includes attachment, empathy, and social play. 4. Language Development: Progression from cooing to babbling, word formation, and sentence building. 5. Adaptive Behavior: Development of self-care skills like eating, dressing, and toileting. Bayley Scales of Infant and Toddler Development (Bayley-III) Introduction: The Bayley Scales are a standardized tool used to assess the developmental progress of children aged 1 to 42 months. It evaluates multiple domains of development to identify delays or disabilities and guide interventions. Purpose: 1. Monitor development in infants and toddlers. 2. Detect early signs of developmental delays. 3. Aid in planning early intervention strategies. Structure of the Bayley Scales: The Bayley Scales consist of five main domains: 1. Cognitive Scale: Assesses problem-solving abilities and exploration of the environment. Examples: Attention to objects. Imitative play. Ability to follow simple instructions. 2. Language Scale: Resume pt 2 6  Divided into receptive language (understanding) and expressive language (speaking). Examples: Receptive: Responding to commands or pointing to pictures. Expressive: Babbling, naming objects, forming sentences. 3. Motor Scale: Evaluates fine and gross motor skills. Examples: Fine motor: Grasping, stacking blocks, scribbling. Gross motor: Rolling, crawling, standing, walking, and climbing. 4. Social-Emotional Scale: Measures emotional regulation, social interactions, and adaptability. Based on parental questionnaires and observations. 5. Adaptive Behavior Scale: Assesses daily living skills and independence. Examples: Feeding, dressing, toileting. Interaction with family and peers. Administration and Scoring: 1. Age Range: Designed for children 1–42 months of age. 2. Testing Procedure: Conducted by trained professionals, typically lasting 50–90 minutes. Involves a combination of direct testing and parent questionnaires. 3. Scoring: Standardized scores are generated for each domain. Percentiles and developmental age equivalents are provided. Resume pt 2 7  Helps identify if the child is within the normal range or delayed. 4. Interpretation: Scores can help distinguish between typical development, delays, or specific developmental disabilities. Clinical Applications of the Bayley Scales 1. Early Identification of Delays: Provides an objective measure of developmental progress to detect conditions like autism spectrum disorder (ASD), cerebral palsy, or global developmental delay. 2. Guidance for Early Intervention: Results help tailor intervention programs to address specific delays (e.g., speech therapy for language delays). 3. Monitoring High-Risk Infants: Particularly useful for preterm infants, those with birth complications, or those exposed to adverse environments. 4. Research and Assessment: Widely used in research to study early development and the impact of interventions. Developmental Milestones (Bayley Context) Domain Typical Milestones (By Age) 6 months: Explores with hands/mouth; 12 months: Follows simple Cognitive instructions. 6 months: Babbling; 12 months: Says simple words; 24 months: Language Combines 2 words. 6 months: Rolls over; 12 months: Stands alone; 18 months: Walks Motor independently. Social- 6 months: Smiles at people; 12 months: Stranger anxiety; 24 months: Emotional Parallel play. Adaptive 12 months: Drinks from a cup; 24 months: Begins dressing self. Resume pt 2 8  Benefits and Limitations of the Bayley Scales Benefits: 1. Comprehensive assessment across multiple domains. 2. Standardized scoring ensures consistency. 3. Identifies early developmental delays, facilitating timely interventions. 4. Provides valuable insights for parents and caregivers. Limitations: 1. Requires trained professionals for administration. 2. Time-consuming for both the examiner and the child. 3. Performance may be influenced by the child’s mood or environmental factors during testing. Comparison to Other Developmental Tools Denver Developmental Aspect Bayley Scales Screening Test (DDST) Age Range 1–42 months Birth–6 years Domains Cognitive, Language, Motor, Personal-Social, Fine Motor, Assessed Social-Emotional, Adaptive Language, Gross Motor Purpose Comprehensive assessment Screening for delays Administration Requires trained professional Simple and quicker Key Points 1. The Bayley Scales of Infant and Toddler Development are essential for assessing developmental progress in children up to 42 months of age. 2. It evaluates five key domains: cognitive, language, motor, social- emotional, and adaptive behaviors. 3. Results guide early intervention strategies, particularly for high-risk infants or those with suspected delays. 4. While comprehensive, the test requires professional administration and may not capture all aspects of a child’s development in a single session. Resume pt 2 9  Brain in Puberty: Revised Super-Complete Exam Preparation Resume 1. Adolescence: Definition and Characteristics Adolescence is the transitional phase of development between childhood and adulthood. It encompasses biological, psychological, and social changes, primarily influenced by hormonal surges and brain maturation. Key Characteristics: 1. Physical: Puberty onset, marked by: Development of secondary sexual characteristics (e.g., breast development, facial hair). Activation of the hypothalamic-pituitary-gonadal (HPG) axis. Accelerated growth (pubertal growth spurt). Hormonal surges: Increased gonadal hormones like testosterone and estrogen. 2. Cognitive: Shift from concrete to abstract thinking. Development of critical reasoning and problem-solving skills. Prefrontal cortex (PFC) development enhances executive functions like planning and emotional regulation. 3. Behavioral: Increased risk-taking behaviors and novelty-seeking. Heightened peer influence and sensitivity to social rewards. 4. Environmental: Adolescents redefine relationships with parents, transitioning toward independence. Greater exposure to external influences (e.g., media, social groups). Resume pt 2 10  Stages of Adolescence: 1. Early Adolescence (10–14 years): Dominated by physical changes. High emotional sensitivity due to early limbic system activation. 2. Middle Adolescence (15–17 years): Intensified focus on social interactions and identity formation. Heightened risk-taking behaviors. 3. Late Adolescence (18–21+ years): Prefrontal cortex matures, leading to improved impulse control and decision-making. 2. Brain Development During Adolescence 2.1 Grey Matter Changes: Synaptic Pruning: The brain eliminates unused neural connections, increasing efficiency. Begins in sensorimotor areas and progresses to the prefrontal cortex. Allows for specialization of neural networks based on environmental demands. Decrease in Grey Matter: ~15% reduction during adolescence, indicating pruning. 2.2 White Matter Changes: Myelination: Axons are coated with myelin, improving signal transmission speed and efficiency. White matter volume increases in areas like the corpus callosum (connecting brain hemispheres), enhancing integration between brain regions. 2.3 Brain Regions in Development: Resume pt 2 11  1. Prefrontal Cortex (PFC): Responsible for executive functions like planning, impulse control, and social behavior. Matures late, contributing to the “maturity gap” seen in adolescents. 2. Limbic System: Includes structures like the amygdala and striatum. Regulates emotion and reward-seeking behaviors. Develops early, driving sensation-seeking behaviors before inhibitory systems mature. 3. Behavioral Implications of Brain Development 3.1 Impulsivity and Risk-Taking: The limbic system is hyperactive, and the PFC is underdeveloped. Adolescents prioritize short-term rewards over long-term consequences, increasing engagement in risky activities. 3.2 Emotional Sensitivity: Heightened amygdala activity causes stronger emotional responses. Peer approval activates the striatum, reinforcing social behaviors. 3.3 Decision-Making Under Stress: Stress disrupts adolescent decision-making due to increased cortisol sensitivity. Stress-response systems are still maturing, leading to overreactions in high-pressure situations. 4. Effects of Substance Use on the Adolescent Brain Substance use during adolescence exploits the developing reward system, increasing the risk of long-term dependency and cognitive impairments. 4.1 Alcohol: Targets the prefrontal cortex, impairing decision-making and memory. Resume pt 2 12  Prolonged use disrupts synaptic pruning and myelination. 4.2 Cannabis: Affects CB1 receptors in the hippocampus, leading to: Memory impairments. Disruption in neural plasticity. 4.3 Nicotine: Activates nicotinic acetylcholine receptors, leading to dependence. Inhibits normal synaptic pruning and increases the risk of addiction. 4.4 Party Drugs (e.g., Ecstasy/MDMA): Damages serotonin transporters, impairing mood regulation and memory. 5. Clinical and Social Implications 5.1 Clinical: Mental health disorders (e.g., anxiety, depression) often emerge during adolescence due to brain vulnerability. Substance abuse during this period can have lifelong effects on cognition and behavior. 5.2 Social: Adolescents are more likely to engage in peer-influenced risky behaviors. Education about brain development and healthy decision-making can mitigate risks. Key Points for Exam 1. Adolescence is a critical period for physical, cognitive, and emotional development, driven by hormonal changes and brain maturation. 2. The maturity gap between the limbic system and prefrontal cortex explains increased impulsivity and sensation-seeking behaviors. Resume pt 2 13  3. Substances like alcohol, nicotine, and cannabis disrupt normal brain development, with long-term consequences. 4. Understanding brain changes during adolescence can guide interventions in education, mental health, and youth healthcare. This expanded version includes in-depth physiological mechanisms, specific examples, and clinical relevance to help solidify your understanding. Let me know the next PowerPoint, and I’ll maintain this level of detail! Sexually Transmitted Infections (STIs): Super- Complete Exam Resume 1. Overview of STIs Definition: STIs are infections caused by bacteria, viruses, or parasites and are transmitted primarily through sexual contact (vaginal, anal, or oral sex). They may also be transmitted vertically (from mother to child) during pregnancy or delivery. Global Impact: Among the most common communicable diseases globally. Affected individuals are often unaware of their infection, leading to higher transmission rates and severe complications. Key Complications: Reproductive health: Infertility. Ectopic pregnancy. Chronic pelvic pain. Fetal and neonatal outcomes: Congenital infections (e.g., syphilis). Resume pt 2 14  Neonatal conjunctivitis or pneumonia. Increased risk of HIV acquisition. 2. Classification of STIs 2.1 Bacterial STIs: 1. Chlamydia: Caused by Chlamydia trachomatis. Symptoms: Often asymptomatic. Urethritis, cervicitis, pelvic inflammatory disease (PID). Complications: Infertility, ectopic pregnancy, neonatal conjunctivitis. Treatment: Antibiotics (e.g., azithromycin or doxycycline). 2. Gonorrhea: Caused by Neisseria gonorrhoeae. Symptoms: Urethritis in men, cervicitis in women. Can cause rectal or pharyngeal infection. Complications: PID, infertility, neonatal blindness. Treatment: Antibiotics (e.g., ceftriaxone with azithromycin). Increasing antibiotic resistance is a challenge. 3. Syphilis: Caused by Treponema pallidum. Stages: Primary: Painless chancre. Resume pt 2 15  Secondary: Rash, fever, systemic symptoms. Tertiary: Neurosyphilis, cardiovascular damage. Congenital syphilis can cause severe neonatal complications. Treatment: Penicillin. 4. Trichomoniasis: Caused by Trichomonas vaginalis (a protozoan parasite). Symptoms: Vaginal discharge, itching, dysuria. Treatment: Metronidazole. 2.2 Viral STIs: 1. Human Papillomavirus (HPV): Most common STI globally. High-risk types (16, 18) cause cervical cancer. Prevention: HPV vaccine. Regular Pap smears. No cure; treatment is symptomatic (e.g., removal of warts). 2. Hepatitis B: Transmitted through sexual contact or vertically. Complications: Chronic liver disease, cirrhosis, hepatocellular carcinoma. Prevention: HBV vaccine. 3. Herpes Simplex Virus (HSV): HSV-1 and HSV-2. Resume pt 2 16  Symptoms: Painful genital ulcers, recurrent outbreaks. No cure; antivirals (e.g., acyclovir) reduce symptoms. 4. HIV: Increases susceptibility to other STIs. Management includes antiretroviral therapy (ART). 3. STI Diagnosis Methods: 1. Clinical Examination: Inspection of genital ulcers, discharge, or rashes. 2. Laboratory Testing: Microscopy (e.g., Trichomonas vaginalis motility). Culture and nucleic acid amplification tests (NAAT) for Chlamydia and Gonorrhea. Serology for syphilis and HIV. Screening Recommendations: High-risk populations: All sexually active women under 25. Pregnant women should be screened for syphilis, chlamydia, gonorrhea, and HIV. 4. Treatment of STIs General Principles: 1. Antibiotics for bacterial STIs: Simultaneous treatment of partners is essential. 2. Antiviral therapy for viral STIs: No cure; focus on symptom management and reducing transmission. Resume pt 2 17  3. Vaccination: HPV and HBV vaccines for prevention. 5. Prevention of STIs 1. Safe Sex Practices: Consistent condom use. Reducing the number of sexual partners. 2. Vaccination: HPV vaccine protects against high-risk strains. HBV vaccine prevents hepatitis B infection. 3. Health Education: Awareness campaigns to encourage early testing and treatment. 6. Epidemiology of STIs Global Trends: STIs disproportionately affect women and young adults. Urban areas with higher population density report higher rates. STIs in Portugal: Regions: Lisbon and Porto have the highest notification rates. Prevalence (2015–2017): Syphilis: 51.5%. Gonorrhea: 33.2%. Chlamydia: 15.3%. 7. Key Points for Exam 1. STI Classification: Resume pt 2 18  Understand bacterial, viral, and parasitic pathogens and their complications. 2. Diagnosis: Laboratory methods, clinical signs, and screening recommendations. 3. Treatment: Targeted antibiotics, antivirals, and vaccination. 4. Prevention: Emphasize condom use, vaccination, and public health strategies. 5. Epidemiology: Key regions and populations at risk globally and in Portugal. From Cell to Tumor: Super-Complete Exam Resume 1. Cancer: An Overview 1.1. Definition: Cancer is a disease characterized by uncontrolled and abnormal cell growth. It arises from genetic mutations in normal cells, leading to the development of neoplasms (tumors). 1.2. Tumor Classification: 1. Benign Tumors: Non-invasive, localized growths. Do not metastasize. 2. Malignant Tumors: Invasive growth with potential to metastasize. Can cause systemic damage. 1.3. Cancer as a Global Problem: Leading cause of mortality worldwide. Resume pt 2 19  Risk factors include genetic predisposition, environmental exposures, and lifestyle factors. 2. Tumorigenesis: The Process of Cancer Formation 2.1. Initiating Factors: 1. Endogenous Mutagens: DNA replication errors. Reactive oxygen species (ROS) causing DNA damage. Examples: Depurination, deamination, oxidation. 2. Exogenous Mutagens: Radiation: Ionizing (X-rays) and ultraviolet (UV) radiation. Chemical Mutagens: Polycyclic hydrocarbons, alkylating agents. Biological Agents: Viruses: Human Papillomavirus (HPV), Hepatitis B/C, Epstein-Barr Virus (EBV). 3. Hereditary Syndromes: Familial Adenomatous Polyposis (FAP): APC gene mutation. Hereditary Breast and Ovary Cancer (HBOC): BRCA1/BRCA2 mutations. Lynch Syndrome: Defects in mismatch repair genes (e.g., MLH1, MSH2). 3. Hallmarks of Cancer Cancer progression involves key biological capabilities that allow tumor survival and proliferation. These hallmarks were expanded in 2000, 2011, and 2022: Core Hallmarks: 1. Sustaining Proliferative Signaling: Persistent activation of growth factor pathways. Mechanisms: Autocrine loops, receptor mutations, and downstream signaling. 2. Avoiding Growth Suppressors: Resume pt 2 20  Inactivation of tumor suppressor genes like RB1 and TP53. 3. Resisting Cell Death: Anti-apoptotic factors block programmed cell death. Example: Upregulation of pro-survival networks. 4. Enabling Replicative Immortality: Telomerase activation prevents telomere shortening, bypassing cellular senescence. 5. Inducing Angiogenesis: Tumors promote blood vessel formation via VEGF, ensuring nutrient and oxygen supply. 6. Activating Invasion and Metastasis: Epithelial-to-Mesenchymal Transition (EMT) increases mobility and invasiveness. Factors: MMPs, integrins, loss of cell adhesion. Emerging Hallmarks: 1. Genome Instability and Mutation: Accumulation of mutations due to defective DNA repair mechanisms. 2. Deregulating Cellular Metabolism: Warburg Effect: Increased glycolysis under normoxic conditions. 3. Tumor-Promoting Inflammation: Immune cells release cytokines and ROS, enhancing tumor growth. 4. Avoiding Immune Destruction: Tumors evade immune surveillance by inhibiting T-cell activity. New Dimensions (2022): Unlocking Phenotypic Plasticity: Tumor cells adapt to changing environments. Nonmutational Epigenetic Reprogramming: Resume pt 2 21  Reversible modifications to gene expression. Polymorphic Microbiomes: Gut and tumor microbiota influence cancer progression. 4. Key Molecular Players 4.1. Oncogenes: Mutated genes promoting uncontrolled cell proliferation. Examples: RAS, MYC, BCR-ABL. 4.2. Tumor Suppressor Genes: Prevent uncontrolled growth. Examples: p53 (TP53): Regulates DNA repair, apoptosis, and cell cycle. Mutations in p53 are common in many cancers. 5. Clonal Evolution of Cancer 1. Definition: Tumor progression is driven by successive clonal expansions of mutated cells. 2. Mechanisms: Mutations confer selective growth advantages. Chemotherapy may eliminate sensitive clones but allow resistant clones to dominate. 6. Metastasis 6.1. Pathophysiology: Tumor cells break through the basement membrane, invade blood/lymphatic vessels, and colonize distant sites. Key steps: EMT, vascular dissemination, and colonization. Resume pt 2 22  6.2. Clinical Implications: Common metastatic sites: Bone: Breast, prostate cancer. Liver: Colorectal cancer. Lungs: Many solid tumors. Imaging: PET-CT, MRI, and bone scans are crucial for staging. 7. Cancer Diagnosis 7.1. Diagnostic Tools: Imaging: X-rays, CT, MRI, ultrasound. Biopsy: Histopathological examination for definitive diagnosis. Molecular Testing: Identify mutations (e.g., BRCA, EGFR) for targeted therapy. 7.2. Prognostic and Predictive Factors: Prognostic: Overall survival likelihood (e.g., stage, grade). Predictive: Response to specific treatments (e.g., HER2 in breast cancer). 8. Cancer Treatment 8.1. Local Treatments: 1. Surgery: Curative for localized tumors. Palliative in advanced cases to relieve symptoms. 2. Radiotherapy: Targets localized tumor cells. Side effects: Fatigue, skin changes. 8.2. Systemic Therapies: Resume pt 2 23  1. Chemotherapy: Targets rapidly dividing cells. Side effects: Myelosuppression, nausea, alopecia. 2. Targeted Therapy: Inhibits specific molecular pathways (e.g., EGFR inhibitors). 3. Immunotherapy: Boosts the immune system (e.g., checkpoint inhibitors like PD-1/PD-L1 blockers). 4. Hormonal Therapy: Blocks hormones that fuel certain cancers (e.g., tamoxifen for breast cancer). 8.3. Palliative Care: Focus on symptom management and quality of life. Includes pain relief and psychological support. 9. Ethical Aspects in Oncology 1. Oncogenetics: Genetic testing raises issues of privacy, psychological impact, and family implications. 2. End-of-Life Decisions: Advanced care planning, palliative sedation, and euthanasia require ethical considerations. Key Takeaways 1. Cancer Formation: Driven by genetic mutations and environmental factors. 2. Hallmarks of Cancer: Framework to understand tumor biology. 3. Metastasis: Resume pt 2 24  Key factor in prognosis and treatment decisions. 4. Treatment: Multimodal approach combining surgery, radiotherapy, systemic therapies, and palliative care. Inheritable Tumors and Ethical Aspects: Exam Resume 1. Overview of Inheritable Tumors Definition: Inheritable tumors arise due to genetic mutations passed through families, leading to increased susceptibility to cancer. Key Syndromes: 1. Hereditary Breast and Ovarian Cancer (HBOC): Genes involved: BRCA1 (chromosome 17q21) and BRCA2 (chromosome 13q12-13). Cancers associated: Breast (early onset), ovarian, prostate, melanoma, pancreatic. Inheritance: Autosomal dominant. 2. Familial Adenomatous Polyposis (FAP): Gene: APC (tumor suppressor). Features: Hundreds of colonic polyps from age 10–12; nearly 100% risk of colorectal cancer. Inheritance: Autosomal dominant. 3. Li-Fraumeni Syndrome (LFS): Gene: TP53 (tumor suppressor). Cancers: Sarcomas, breast, brain, adrenocortical, and leukemias. Inheritance: Autosomal dominant. Resume pt 2 25  4. Multiple Endocrine Neoplasia Type 2A (MEN2A): Gene: RET. Cancers: Medullary thyroid cancer (100% risk without intervention), pheochromocytoma. Inheritance: Autosomal dominant. 2. Genetic Counseling Definition: A process to provide individuals and families with information about inheritable conditions, risks, management options, and psychological support. Aims: 1. Help families understand the disease and inheritance patterns. 2. Offer reproductive options and risk assessment. 3. Support decision-making regarding genetic testing and preventive measures. Process: Carried out by clinical geneticists in specialized settings. Involves discussions about: Risk of disease development. Transmission to offspring. Management strategies. 3. Genetic Testing Types of Tests: 1. Clinical/Diagnostic Tests: Confirm a genetic disease in symptomatic individuals. Help assess the risk in family members. Resume pt 2 26  2. Predictive/Presymptomatic Tests: Identify carriers of pathogenic mutations who are at risk of developing a disease. Examples: Huntington's disease (HD): A trinucleotide repeat disorder with 100% penetrance. HBOC, FAP, and MEN2A (with preventive options). Applications: Prenatal diagnosis. Preimplantation genetic testing (PGT) for reproductive choices. Legal Framework (Portugal - Law 12/2005): Requires: Written informed consent. Genetic counseling before and after testing. Results are confidential and cannot be disclosed to third parties without explicit consent. 4. Ethical Considerations 4.1. Principles of Biomedical Ethics: 1. Autonomy: Respecting an individual’s right to make decisions. Example: Right to refuse testing. 2. Beneficence: Acting in the patient’s best interest. 3. Non-Maleficence: Avoiding harm; minimizing psychological stress of knowing results. 4. Justice: Fair access to genetic testing and treatments. Resume pt 2 27  4.2. Ethical Dilemmas: Should a child undergo predictive testing?: Against: Right to "not know." Lack of immediate benefit. For: Imminent health risks justify testing. Example: Testing children for FAP at 12–14 years. Sharing genetic information with relatives: Conflicts of duty between confidentiality and preventing harm. Overruling confidentiality is permissible in cases of high risk and actionable prevention (e.g., MEN2A and prophylactic thyroidectomy). 5. Protocol for Predictive Testing Inclusion Criteria: 1. Voluntariness (autonomy). 2. Competence (mental capacity to consent). 3. Majority (testing of minors only if it benefits them directly). Preparation for Testing: 1. Pre-test Counseling: Explain pros, cons, and limitations. Discuss potential outcomes and their implications. 2. Medical Information: Comprehensive education about the condition, inheritance, and management. Post-Test Counseling: 1. Help integrate results into life planning. 2. Options after positive results: Resume pt 2 28  Preventive measures (e.g., surgery for HBOC). Reproductive decisions (e.g., PGT). 3. Participation in clinical trials or research. 6. Case Studies and Implications 6.1. Huntington’s Disease (HD): Key Features: Autosomal dominant. Complete penetrance. Progressive neurodegeneration; no cure. Predictive Testing: High psychological impact; requires counseling. Used as a model for other genetic conditions. 6.2. HBOC: Management: Screening: Yearly MRIs (from age 25) and mammograms (from age 30). Prophylactic mastectomy and oophorectomy (timing depends on BRCA mutation). PGT for reproductive options. 6.3. MEN2A: Management: Prophylactic thyroidectomy prevents medullary thyroid cancer. Genetic testing in at-risk individuals ensures early intervention. 7. Key Takeaways 1. Inheritable Tumors: High risk but manageable with early detection and preventive measures. Resume pt 2 29  2. Genetic Counseling: Critical for informed decision-making and psychological support. 3. Ethical Challenges: Balancing autonomy, beneficence, and confidentiality. 4. Testing Protocols: Structured approaches ensure ethical and legal compliance. 5. Preventive Measures: Screening, prophylactic surgeries, and reproductive technologies improve outcomes. Neoplasia and Molecular Pathology: Super- Complete Exam Resume 1. Neoplasia Overview Definition: A disorder of cell growth triggered by acquired mutations, leading to an abnormal mass of tissue: Cells grow and divide excessively. Cells fail to die when they should. Basic Components: 1. Neoplastic Cells: Tumor parenchyma. 2. Reactive Stroma: Includes connective tissue, blood vessels, and immune cells. 2. Classification of Neoplasms 2.1. By Behavior: 1. Benign Tumors: Localized, non-invasive. Resume pt 2 30  Examples: Adenoma (epithelial origin). Lipoma (adipose tissue). 2. Malignant Tumors (Cancer): Invasive and metastatic. Examples: Carcinomas (epithelial origin): Squamous cell carcinoma, adenocarcinoma. Sarcomas (mesoderm origin): Osteosarcoma, chondrosarcoma. 2.2. By Origin: 1. Ectoderm/Endoderm: Malignant: Carcinomas (e.g., squamous cell carcinoma, adenocarcinoma). 2. Mesoderm: Malignant: Sarcomas (e.g., osteosarcoma, leiomyosarcoma). 3. Mixed Tumors: Contain multiple cell types (e.g., pleomorphic adenoma). 4. Blastomas: Resemble primitive embryonic tissues; often seen in pediatric cancers (e.g., neuroblastoma, hepatoblastoma). 3. Key Features of Malignancy 1. Invasion: Destruction of surrounding tissues. 2. Metastasis: Spread to distant sites via lymphatics, blood, or direct seeding. 3. Angiogenesis: Formation of new blood vessels to sustain tumor growth. Resume pt 2 31  4. Hallmarks of Cancer 1. Sustaining Proliferative Signaling: Growth factors and receptor mutations drive unregulated division. 2. Evading Growth Suppressors: Loss of tumor suppressor genes like TP53, RB1. 3. Resisting Cell Death: Avoid apoptosis through overexpression of anti-apoptotic proteins (e.g., BCL-2). 4. Limitless Replicative Potential: Activation of telomerase allows continuous division. 5. Inducing Angiogenesis: VEGF promotes vascularization. 6. Invasion and Metastasis: Enabled by epithelial-to-mesenchymal transition (EMT) and matrix metalloproteinases (MMPs). Emerging hallmarks include immune evasion and metabolic deregulation (e.g., Warburg effect). 5. Tumor Grading and Staging 5.1. Grading: Grade: Measures how abnormal tumor cells/tissues appear microscopically. Examples: Breast Tumor Grading: Nottingham grading system evaluates mitosis, nuclear pleomorphism, and glandular differentiation. Prostate Grading: Gleason score assesses patterns of glandular architecture. 5.2. Staging: TNM System: T: Tumor size and invasion depth. Resume pt 2 32  N: Lymph node involvement. M: Presence of metastases. Stages: I–IV, based on severity and spread. 6. Molecular Pathology in Cancer 6.1. Immunohistochemistry: Identifies tumor origin and molecular markers using specific antibodies. Common markers: Epithelial: Cytokeratins. Neuroendocrine: Chromogranin A, NSE. Melanoma: HMB45, S100. Leukocytes: CD3 (T cells), CD20 (B cells). Proliferation: Ki-67. 6.2. Molecular Markers for Diagnosis: Genetic Mutations: Lynch Syndrome: Mismatch repair genes (MLH1, MSH2). HER2: Predictive in breast cancer therapy. Hormone Receptors: Estrogen and progesterone in breast cancer. 7. Pathophysiology of Neoplasia 7.1. Genetic Mutations: Oncogenes: Promote proliferation. Examples: RAS, MYC, EGFR. Tumor Suppressor Genes: Resume pt 2 33  Inhibit proliferation. Examples: TP53, APC. 7.2. Metastatic Cascade: 1. Local Invasion: EMT reduces cell adhesion (E-cadherin loss). 2. Intravasion: Entry into lymphatic or blood vessels. 3. Survival in Circulation: Evade immune cells. 4. Extravasation: Exit vessels and invade distant tissues. 5. Colonization: Establish secondary tumors. 8. HPV and Cervical Cancer 8.1. Pathogenesis: HPV infects epithelial cells, integrating its DNA into the host genome. Causes overexpression of E6 and E7 proteins: E6 degrades TP53. E7 inactivates RB1. 8.2. Clinical Stages: LSIL (Low-Grade Squamous Intraepithelial Lesion): Often resolves spontaneously. HSIL (High-Grade Squamous Intraepithelial Lesion): May progress to invasive cancer. 9. Cases Highlighted in Pathology Case 1: Leiomyoma (Benign) vs. Leiomyosarcoma (Malignant) Resume pt 2 34  Leiomyoma: Localized, well-demarcated, non-invasive. Leiomyosarcoma: Invasive, high mitotic activity. Case 2: HPV and Precancerous Lesions Progression from CIN1 → CIN2 → CIN3 → Cervical Cancer. Case 3: Breast Cancer Fibroadenoma: Benign. Invasive Ductal Carcinoma: Malignant with lymphovascular invasion. 10. Key Points for Exam 1. Neoplasia involves abnormal growth driven by genetic mutations. 2. Classification of tumors includes benign vs. malignant and by tissue of origin. 3. Hallmarks of Cancer provide a framework for understanding tumor biology. 4. Grading and staging are critical for determining prognosis and treatment. 5. Molecular techniques like immunohistochemistry identify tumor markers and therapeutic targets. 6. HPV’s role in cervical cancer highlights the interplay between viruses and cancer. Neoplasia and Molecular Pathology: Part 2 - Exam Resume 1. DNA Mutations Definition: Alterations in the DNA sequence that may affect genes and contribute to diseases like cancer. Mutations arise from: Cell division errors. Resume pt 2 35  Environmental damage (e.g., UV rays, chemicals). Types of DNA Mutations: 1. Point Mutations: Single nucleotide changes (e.g., missense, nonsense mutations). 2. Chromosomal Mutations: Large-scale changes, including translocations (e.g., Philadelphia chromosome in CML). 3. Copy Number Variations: Duplications or deletions of DNA segments. Types of Origin: 1. Germline Mutations: Inherited from parents and present in every cell. Examples: BRCA mutations in hereditary cancers. 2. Somatic Mutations: Acquired during life due to environmental or replication errors. 2. Genetic Disorders and Cancer Genetic mutations lead to genetic disorders affecting health, with some increasing cancer susceptibility. Examples: Hereditary Non-Polyposis Colorectal Cancer (HNPCC): Lynch syndrome. Familial Adenomatous Polyposis (FAP). Prevention of Somatic Mutations: Minimize UV exposure (use sunscreen). Avoid smoking and harmful chemicals. Maintain a healthy diet and exercise regularly. Vaccinations (e.g., HPV for cervical cancer prevention). Resume pt 2 36  3. Molecular Pathology Applications: 1. Immunohistochemistry (IHC): Identifies tumor origin and molecular markers. Hormone receptor status for breast cancer (e.g., ER, PR, HER2). Diagnostic and predictive utility (e.g., p16 for high-grade squamous lesions). 2. Molecular Testing Techniques: Genotyping: Identifies viral DNA in tumors. FISH (Fluorescence In Situ Hybridization): Detects specific DNA sequences (e.g., HER2 amplification). PCR (Polymerase Chain Reaction): Amplifies DNA for mutation detection. NGS (Next-Generation Sequencing): Comprehensive genetic profiling of tumors. Key for precision medicine (e.g., EGFR mutations in lung cancer). 4. HPV and Cervical Carcinoma HPV Infection: Most HPV infections resolve spontaneously, but persistent infection with high-risk genotypes (e.g., HPV 16, 18) may progress to cancer. Pathogenesis: 1. Latent Infection: Asymptomatic phase. 2. Persistent Infection: Failure to clear the virus. 3. Precancerous Lesions: Low-Grade Intraepithelial Lesion (LSIL): Reversible. High-Grade Intraepithelial Lesion (HSIL): Risk of progression to cancer. 4. Cervical Cancer: Resume pt 2 37  Requires years of progression from HSIL. Screening and Diagnosis: Pap Smear: Detects cytological abnormalities. HPV DNA Testing: Identifies high-risk genotypes. p16 IHC: Marker for HSIL. 5. Molecular Subtypes of Breast Cancer Key Subtypes: 1. Luminal A (HR+/HER2-): Most common and least aggressive. Responsive to hormone therapy. 2. Luminal B (HR+/HER2+): Intermediate prognosis; requires hormone and targeted therapies. 3. Triple-Negative (HR-/HER2-): Poor prognosis; limited treatment options. More common in younger patients. 4. HER2-Positive: HER2 amplification drives tumor growth. Targeted therapies: Trastuzumab (Herceptin). Treatment: Hormonal Therapy: ER/PR-positive cancers. HER2 Targeted Therapy: HER2-positive cancers. Chemotherapy: Aggressive or refractory cases. 6. Microsatellite Instability (MSI) and Mismatch Repair (MMR) Definition: MSI: Length variability in DNA microsatellites due to replication errors. Resume pt 2 38  MMR Deficiency: Caused by mutations in MLH1, MSH2, MSH6, or PMS2. Leads to MSI and predisposes to Lynch syndrome. Clinical Applications: Prognosis: MSI-high tumors have better outcomes. Predictive Value: Defines benefit from immunotherapy (e.g., checkpoint inhibitors). 7. Advances in Molecular Testing Next-Generation Sequencing (NGS): Enables multiplex testing of numerous genes simultaneously. Applications: Identification of actionable mutations (e.g., EGFR, ALK in lung cancer). Tailored treatment plans based on tumor genetics. Circulating Tumor DNA (ctDNA): Non-invasive method to monitor tumor dynamics. Used for: Detecting residual disease post-treatment. Monitoring response to therapy. 8. Summary of Case Studies 1. Cervical Carcinoma: HPV-associated progression from LSIL → HSIL → Cancer. 2. Breast Cancer: Molecular subtypes dictate treatment and prognosis. 3. Colon Cancer: MSI/MMR testing aids in Lynch syndrome identification and therapy decisions. Resume pt 2 39  Key Takeaways 1. DNA Mutations form the foundation of cancer development. 2. HPV is a critical driver of cervical cancer, with effective screening and vaccines. 3. Molecular diagnostics like IHC, FISH, and NGS are essential for modern oncology. 4. Tumor subtypes and genetic profiles guide targeted treatment and prognosis. Molecular Basis of Oncology Treatments: Super- Complete Exam Resume 1. Overview of Cancer Treatments 1.1 Historical Perspective: 1550 BC: Cancer documented in the Ebers Papyrus, with no available treatment. 200 AD: Early surgical treatments by Aelius Galenus. 20th Century: Discovery of chemotherapy during WWII (mustard gas effects). Molecular advances in the 1970s-1980s with cancer-associated gene discoveries. 1.2 Modern Cancer Therapy: Treatment strategies are rooted in the molecular basis of cancer biology, targeting key processes like: DNA synthesis and repair. Cell cycle regulation. Tumor-host interactions. 1.3 Pillars of Cancer Therapy: Resume pt 2 40  1. Local Therapies: Surgery: Physical removal of tumors. Radiotherapy: Focused radiation to destroy cancer cells. 2. Systemic Therapies: Chemotherapy: Broadly destroys dividing cells. Targeted Therapy: Specifically disrupts molecular pathways. Immunotherapy: Harnesses the immune system against cancer. Endocrine Therapy: Hormonal manipulation. Cell-Based Therapies: Includes CAR-T cells. 2. Targeting DNA and Cell Cycle Machinery 2.1 Chemotherapy: Exploits rapid division and defective DNA repair in cancer cells. Types: 1. Cell Cycle-Specific Drugs: Act during specific phases (e.g., taxanes for mitotic phase). 2. Cell Cycle-Non-Specific Drugs: Active during both resting and cycling phases (e.g., platinum salts). 2.2 Examples of Chemotherapeutic Agents: 1. Platinum Salts (e.g., Cisplatin, Carboplatin): Form DNA crosslinks, causing strand breakage and apoptosis. 2. Topoisomerase Inhibitors: Block enzymes that manage DNA supercoiling, leading to DNA damage. Top I inhibitors: Irinotecan. Top II inhibitors: Etoposide. 3. Taxanes: Stabilize microtubules, preventing spindle disassembly and mitosis. Resume pt 2 41  Examples: Paclitaxel, Docetaxel. 4. CDK4/6 Inhibitors: Target cyclin-dependent kinases, halting the G1/S phase transition. Examples: Palbociclib. 3. Modulating Cell Signaling 3.1 Growth Factor Receptors: Receptor Tyrosine Kinases (RTKs) are frequently altered in cancer: Example: HER2 overexpression in breast cancer drives proliferation. 3.2 Targeted Therapies: 1. HER2 Targeting: Trastuzumab (Herceptin): Monoclonal antibody blocking HER2 signaling. Increases immune-mediated destruction of HER2+ cells. Antibody-Drug Conjugates (ADCs): Deliver chemotherapy specifically to HER2+ cells (e.g., trastuzumab deruxtecan). 2. EGFR Mutations in Lung Cancer: Drugs like Erlotinib target EGFR mutations to inhibit cell signaling. 3.3 Intracellular Pathway Inhibitors: RAS-RAF-MEK-ERK Pathway: Frequently hyperactivated in cancers (e.g., KRAS in colorectal cancer, BRAF in melanoma). Targeted drugs: BRAF inhibitors: Vemurafenib for melanoma. MEK inhibitors: Trametinib. 4. Modulating the Immune System Resume pt 2 42  4.1 Immune Checkpoint Inhibitors (ICIs): PD-1/PD-L1 Blockade: Prevents cancer cells from evading immune detection. Examples: Nivolumab, Pembrolizumab. CTLA-4 Inhibitors: Enhance T-cell activation (e.g., Ipilimumab). 4.2 CAR-T Cells: Patient T cells are genetically engineered to express chimeric antigen receptors targeting cancer antigens. Effective for hematologic cancers (e.g., B-cell lymphomas). 4.3 BiTEs (Bi-Specific T-cell Engagers): Artificial antibodies that link T cells to tumor cells, enhancing cytotoxic activity. 5. Chronic Myeloid Leukemia (CML) 5.1 Pathogenesis: Caused by the Philadelphia Chromosome: t(9;22) translocation creates the BCR-ABL1 fusion protein. Constitutive tyrosine kinase activity drives proliferation. 5.2 Targeted Therapy: Imatinib (Gleevec): Tyrosine kinase inhibitor (TKI) that specifically blocks BCR-ABL1. 6. Challenges in Oncology Treatments 6.1 Drug Resistance: Mechanisms: Altered drug targets (e.g., mutations in BRAF). Resume pt 2 43  Efflux pumps expel drugs from cells. Tumor microenvironment shields cancer cells. Strategies: Combination therapies. Continuous monitoring for resistance mutations. 7. Take-Home Messages 1. Modern cancer therapies are rooted in molecular biology, targeting specific cellular pathways. 2. Targeted therapies (e.g., TKIs, monoclonal antibodies) improve precision and reduce systemic toxicity. 3. Immunotherapy represents a major advance, leveraging the immune system to combat cancer. 4. Challenges like drug resistance require ongoing research and combination strategies. Clinical Oncology: Super-Complete Exam Resume 1. Principles of Cancer Treatment 1.1 Definition of Cancer: Cancer is a disease characterized by uncontrolled cell growth and proliferation due to: Accumulation of genetic mutations. Escape from normal cellular growth control mechanisms. Multi-step process involving genetic and environmental factors. 1.2 Etiology and Risk Factors: 1. Genetic Mutations: Oncogenes (e.g., RAS). Tumor suppressor genes (e.g., TP53, APC). Resume pt 2 44  2. Environmental: Smoking, radiation, infections (e.g., HPV, HBV). 3. Lifestyle: Obesity, alcohol consumption, lack of exercise. 2. Staging and Performance Status 2.1 Tumor Staging (TNM System): 1. Tumor (T): T0: No evidence of tumor. T1-T4: Size and extent of the primary tumor. 2. Node (N): N0: No regional lymph node involvement. N1-N3: Increasing lymph node involvement. 3. Metastasis (M): M0: No distant metastasis. M1: Presence of metastasis. 2.2 Performance Status: Evaluates a patient’s ability to perform daily activities. Common scales: 1. ECOG (Eastern Cooperative Oncology Group): 0: Fully active. 5: Dead. 2. Karnofsky Performance Status (KPS): Scored from 0 to 100, with higher scores indicating better functioning. 3. Anticancer Therapies 3.1 Surgery: Resume pt 2 45  Curative Surgery: R0: Complete resection with no microscopic residual tumor. Palliative Surgery: Reduces tumor burden to relieve symptoms. 3.2 Radiotherapy: 1. Types: External beam radiation. Brachytherapy (radioactive implants). Systemic radioisotopes. 2. Goals: Curative: Eradicate localized disease. Palliative: Alleviate symptoms (e.g., bone pain). 3.3 Chemotherapy: 1. Types: Neoadjuvant: Before surgery to shrink tumors. Adjuvant: After surgery to eliminate residual cells. Palliative: Symptom relief in advanced stages. 2. Mechanisms: DNA damage (e.g., platinum agents). Mitotic inhibitors (e.g., taxanes). 3.4 Immunotherapy: 1. Checkpoint Inhibitors: PD-1/PD-L1 inhibitors (e.g., Nivolumab) prevent immune evasion. 2. CAR-T Cell Therapy: Genetically engineered T cells target cancer antigens. 3.5 Targeted Therapy: Resume pt 2 46  Drugs target specific molecular pathways. 1. Examples: EGFR inhibitors (e.g., Erlotinib). HER2 inhibitors (e.g., Trastuzumab). 3.6 Hormone Therapy: Blocks hormones that fuel cancer growth. Tamoxifen: Estrogen receptor blocker (breast cancer). Anti-androgens: Block testosterone (prostate cancer). 4. Palliative Care 4.1 Terminal Sedation: Sedatives relieve intractable pain. Follows the principle of double effect: intention is pain relief, not hastening death. 4.2 Euthanasia: Legal in some jurisdictions under strict regulations. Requires explicit patient consent and ethical evaluation. 5. Monitoring and Response to Treatment 5.1 Assessment: 1. Clinical Response: Complete response: No tumor evidence. Partial response: Reduction in tumor size. Progressive disease: Tumor growth or new lesions. 2. Imaging and Biomarkers: PET-CT, MRI, and molecular markers (e.g., PSA in prostate cancer). 5.2 Post-Treatment Care: Resume pt 2 47  Surveillance for recurrence. Management of long-term effects (e.g., cardiotoxicity, neuropathy). Psychological support for anxiety and fear of recurrence. Key Takeaways: 1. Cancer therapy involves a multidisciplinary approach, combining surgery, systemic therapies, and supportive care. 2. Staging and performance status guide treatment planning and prognosis. 3. Advances in targeted and immune therapies have revolutionized cancer treatment, improving precision and outcomes. 4. Palliative care focuses on symptom relief and quality of life in advanced stages. Let me know if you'd like further details or the next topic! Multidisciplinary Approach in Oncology: Exam Resume 1. Overview of Multidisciplinary Care in Oncology 1.1 Definition: Multidisciplinary care involves the collaboration of healthcare professionals across different specialties to optimize cancer diagnosis, treatment, and patient care. 1.2 Key Teams: 1. Diagnosis Teams: Pathologists: Analyze biopsy specimens to confirm cancer type and grade. Radiologists: Perform imaging studies (e.g., CT, MRI, PET-CT) for staging. Geneticists: Identify germline or somatic mutations for targeted therapy. Resume pt 2 48  2. Treatment Teams: Surgical Oncologists: Perform tumor resections. Medical Oncologists: Administer chemotherapy, targeted therapy, and immunotherapy. Radiation Oncologists: Plan and deliver radiotherapy. 3. Support Teams: Nurses and Palliative Care Specialists: Provide symptom management and end-of-life care. Nutritionists: Address cancer-related malnutrition. Psychologists: Support mental health and coping mechanisms. 2. Tumor Boards and Multidisciplinary Meetings 2.1 Role: Weekly meetings to discuss patient cases and establish personalized treatment plans. 2.2 Components: 1. Case Presentation: Review of imaging, pathology, and surgical outcomes. 2. Treatment Decisions: Determining the sequence of therapies (e.g., neoadjuvant vs. adjuvant). Selection of systemic therapies based on molecular profiles. 3. Follow-Up: Monitoring treatment response and adjusting strategies. 3. Breast Cancer Case Study 3.1 Diagnosis: 58-year-old woman presenting with a mammographic finding: Pathology: Invasive carcinoma NST (no special type). Resume pt 2 49  ER+, PR+, HER2+ (triple positive). Tumor size: 26 mm. Sentinel node biopsy: No lymph node involvement (pT2N0). 3.2 Treatment Plan: 1. Local Therapy: Breast-conserving surgery (lumpectomy). Sentinel lymph node dissection to evaluate regional spread. Adjuvant radiotherapy for residual microscopic disease. 2. Systemic Therapy: Chemotherapy: 8 cycles (e.g., doxorubicin, cyclophosphamide, and docetaxel). Targeted Therapy: Trastuzumab (Herceptin) for HER2+. Endocrine Therapy: Tamoxifen for 2.5 years followed by aromatase inhibitor for 2.5 years. 3. Post-Treatment Follow-Up: Regular imaging (mammograms, ultrasounds). Monitoring tumor markers and side effects (e.g., cardiotoxicity from trastuzumab). 4. Role of Radiotherapy 4.1 Applications: 1. Adjuvant Radiotherapy: Prevents local recurrence after surgery. Targets breast tissue, chest wall, and regional nodes. 2. Palliative Radiotherapy: Alleviates symptoms in metastatic disease (e.g., bone pain). Resume pt 2 50  4.2 Techniques: Linear Accelerator (LINAC): Precise delivery of high-dose radiation. Delineation and Contouring: Based on surgical margins and imaging data. 5. Advances in Systemic Therapy 5.1 Chemotherapy: Non-specific agents that target rapidly dividing cells. Common drugs for breast cancer: Docetaxel: Microtubule stabilizer. Doxorubicin: DNA intercalator; cardiotoxic in rare cases. 5.2 Targeted Therapy: 1. HER2-Positive Cancer: Trastuzumab and pertuzumab. 2. CDK4/6 Inhibitors: Palbociclib for ER+ breast cancer. 3. PARP Inhibitors: Olaparib for BRCA-mutated cancers. 5.3 Endocrine Therapy: For ER+ cancers: Tamoxifen: Blocks estrogen receptor in premenopausal women. Aromatase inhibitors: Reduce estrogen production in postmenopausal women. 6. Prognostic Factors in Oncology Key Parameters: Resume pt 2 51  1. Tumor size and grade. 2. Hormone receptor status (ER, PR). 3. HER2 status. 4. Proliferation index (Ki-67). 5. Presence of lymph node metastases. Breast Cancer Example: ER+, PR+, HER2+ tumors are aggressive but respond well to targeted and hormonal therapies. 7. Key Takeaways 1. Multidisciplinary care ensures that patients receive comprehensive, personalized treatment. 2. Tumor boards integrate diagnostic, therapeutic, and support teams to optimize outcomes. 3. Advances in systemic therapy, such as HER2-targeted drugs and endocrine therapy, have significantly improved survival rates in breast cancer. 4. Continuous follow-up is critical for monitoring recurrence and managing long-term side effects. Resume pt 2 52