Cancer Epidemiology in Children vs Adults

Learning Objectives

• Differentiate between benign and malignant neoplasms
• Discuss the pathophysiology of malignant disease
• Summarize factors influencing cancer spread
• Identify methods for screening and diagnosing cancer
• Discuss cancer screenings across the lifespan
• Discuss cancer treatment modalities

Cancer

• Cancer is a disease where abnormal cells divide uncontrollably and invade other tissues, destroying healthy cells.
• A tumor is another name for a neoplasm (new growth).
• A hallmark of cancer cells is anaplasia, the loss of cellular differentiation.

Benign vs. Malignant Tumors

• Benign*
• Slow growth and cohesive
• Well-defined borders/capsule
• Local (not invasive)
• Encapsulated (rare dividing cells)
• Easily removed
• Does not recur (does not metastasize)
• Resembles the tissue of origin
• Can progress to malignant
• Malignant*
• Rapid growth and non-cohesive
• Does not stop at tissue borders
• Invades other structures and tissues
• Not encapsulated
• Not always easily removable
• Can recur and spread via blood and lymph
• Poorly differentiated; may not resemble tissue origin
• Named from original cell type

Classification & Nomenclature

• Epithelial tissue = Carcinomas
• Glandular tissue = Adenocarcinomas
• Connective, muscle, & bone tissue = Sarcomas
• Brain & spinal cord tissue = Gliomas
• Pigment cells = Melanomas
• Plasma cells = Myelomas
• Lymphatic tissue = Lymphomas
• Leukocytes = Leukemias

Naming Tumors

• A malignant tumor arising from breast glandular tissue is a mammary adenocarcinoma (arising from glandular cells).
• A benign breast tumor is a fibroadenoma (arising from fibrous tissue).

Carcinoma in Situ (CIS)

• Pre-invasive epithelial tumors (of glandular or squamous cell origin)
• Abnormal growth in epithelial tissues (common in cervix, skin, oral cavity, bronchus, and breast)
• Three possible fates: stable, progress to invasive/metastatic, or regress/disappear.

10 Hallmarks of Cancer

• Transformation*
• Sustained proliferative signaling
• Lack of contact inhibition (“dog pile” effect)
• Autonomy*
• Independence from normal cellular controls
• Increased growth rate, decreased apoptosis
• Development of their own blood supply
• Immortality*
• Unlimited lifespan and continuous division

2. Evading Immune Destruction

• Cancer cells express unique cell surface antigens, not found on normal cells.
• Leads to: lacking T-cell recognition of the tumor, mutations in genes needed for antigen processing, or a failure to produce antigen, inhibiting T-cell activation, producing immunosuppressive proteins, or expressing inhibitory cell surface proteins.

3. Evading Growth Suppressors

• Inactivated tumor-suppressor genes usually regulate cell-cycle, inhibit proliferation, and prevent mutations.
• Inactivation requires at least two mutations (one per allele).
• A single germ-cell mutation can lead to cancer transmission across generations.

4. Enabling Replicative Immortality

• Telomeres protect chromosome ends (cancer cells activate telomerase to maintain telomeres allowing continuous division).
• Normal cells have limited division cycles (apoptosis).

5. Tumor Promoting Inflammation

• Chronic inflammation is a key factor in cancer development (e.g., solar irradiation, asbestos, pancreatitis, infections).
• Certain areas are more susceptible to oncogenic effects of chronic inflammation (e.g., GI tract, prostate, thyroid).
• Inflammatory cells (cytokines, free radicals, mutation promotion, and reduced DNA damage responses) can promote further cancer development.

6. Activating Invasion & Metastasis

• Invasion: local spread required for metastasis
• Metastasis: spread to distant tissues/cells

7. Genomic Instability

• Increased tendency for alterations (mutations) in the genome throughout cell lifecycles, genome integrity disrupted due to inherited/acquired mutations in caretaker genes and DNA repair impacting genomic instability.

8. Inducing Angiogenesis

• Establishing new blood vessels supports tumor growth
• Necessary for cancer growth and spread

9. Resisting Apoptotic Cell Death

• Apoptotic pathways (programmed cell death) are dysregulated in cancer cells; loss of protection against aberrant growth.

10. Deregulating Cellular Energetics

• Cancer cells have different nutritional needs and reprogram energy metabolism.

Risk Factors of Cancer

• Genetic:* Family history, hereditary factors.
• Acquired Diseases:* Ulcerative colitis.
• Viral/Bacterial Infections*
• Lifestyle:* Smoking, obesity, diet, alcohol intake, exposure to carcinogens, radiation exposure, sun exposure, type 2 diabetes, sedentary lifestyle

Early Signs & Symptoms (Caution)

• Changes in bowel/bladder habits
• Persistent sore throat
• Unusual bleeding/discharge
• Thickening/lumps
• Indigestion/dysphagia
• Obvious changes in moles
• Nagging cough/hoarseness
• unexplained weight loss
• pernicious anemia

Clinical Manifestations of Cancer

• Pain:* Little or no pain in early stages, influenced by fear, anxiety, sleep loss, fatigue.
• Fatigue:* Tiredness, lack of energy, due to biochemical changes from disease and treatments, psychosocial factors, activity levels, nutritional status, environmental factors.
• Cachexia:* Severe malnutrition, anorexia, early satiety, weight loss, anemia.
• Anemia:* Hemoglobin decrease, resulting from bleeding, malnutrition, chemotherapy, malignancy in blood-forming organs, erythropoietin deficit.
• Leukopenia & Thrombocytopenia:* Reduced neutrophil/lymphocyte counts due to direct tumor invasion in bone marrow, chemotherapy toxicity.
• Infection:* High risk due to suppressed immune system, reduced WBC/platelet counts
• Gastrointestinal:* Oral ulcers, malabsorption, diarrhea, nausea
• Hair & Skin:* Alopecia (hair loss), skin breakdown, redness, dryness

Diagnosis of Cancer

• Extensive testing to determine tumor presence, its extent, spread, evaluate body system function and tissue/cell analysis for staging and gradient.

Staging of Cancer

• Microscopic analysis for metastasis presence
• Stage I: confined to one spot
• Stage II: spread beyond the original site, but no lymph node involvement.
• Stage III: spread to nearby lymph nodes, but not to distant organs
• Stage IV: Distant metastasis

Tumor Markers

• Biological markers (substances) produced by cancer cells found in blood, CSF, or urine.
• Used for cancer screening and diagnosis, observing clinical cancer progression (hormones, enzymes, antigens, antibodies)
• Problem: false positives/negatives, no marker to screen healthy individuals

Cancer Treatment

• Surgery (preventative, diagnosis, staging)
• Radiation (eradicate, avoid normal structure damage, DNA damage)
• Chemotherapy (specific vulnerabilities, combined treatments)
• Immunotherapy (viral-induced tumors, vaccines, cancer cell vaccines)

Cancer Epidemiology

• Environmental-lifestyle & genetic factors causes cancer.
• Genetic factors influence cancer by external environment.
• Incidence: major cause of morbidity/mortality worldwide.
• Mortality: decreasing in Canada, lung cancer is leading cause of cancer deaths.

Adult Cancers

• Colorectal Cancer*
• Risk factors: advanced age, family hx, ulcerative colitis, diet high in red meat/low fibre, alcohol consumption, smoking, obesity, type 2 diabetes
• Colorectal polyps are associated with cancer development
• Diagnosis: colonoscopy, operative exploration, elevated CEA (carcinoembryonic antigen)
• Subjective:* Change in bowel habits, anorexia, weakness, abdominal cramping, chills.
• Objective:* Diarrhea/constipation, weight loss, rectal bleeding, fever, liver enlargement, palpable mass, signs of obstruction
• Screening:* Start at age 50: flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, double-contrast barium enema every 5 years, CT colonography every 5 years, yearly stool tests (occult blood, stool DNA)
• Prostate Cancer*
• Risk factors: men over 50, familial history, high-fat diet, smoking, vasectomy.
• Diagnosis: digital rectal exam, transrectal ultrasound, CT scan, elevated PSA (prostate-specific antigen)
• Subjective:* difficulty initiating urination, urgency, painful ejaculation, pain due to metastasis, discomfort
• Objective:* Smaller/less forceful urinary stream, terminal dribbling, urinary frequency, nocturia, blood in urine/semen
• Lung Cancer*
• Risk factors: smoking, second-hand smoke, occupational exposures, radiation, air pollution
• Types: squamous cell carcinoma, small cell carcinoma, large cell carcinoma, adenocarcinoma
• Diagnosis: chest X-ray, chest CT, bronchoscopy, transthoracic needle biopsy, further scans for metastasis
• Clinical: Dyspnea, pain, anorexia, history of cigarette smoking, recurrent respiratory infections
• Objective: wheezing, persistent cough, hoarseness, weight loss, positive cytology report, chest pain, signs of metastasis
• Breast Cancer*
• Risk factors: female >50, familial hx, menarche <11, menopause >50, exposure to endogenous estrogens, ionizing radiation, high alcohol/fat intake
• Types: ductal carcinoma in situ, lobular carcinoma in situ
• Diagnosis: mammography, ultrasound, MRI, galactogram, needle aspiration, genetic screening
• Subjective: burning/itching of nipple, reported painless lump
• Objective: firm, non-tender lump/mass, breast asymmetry, nipple retraction, discharge, alterations in breast skin, palpation reveals lump

Cancer in Children & Adolescents

• Incidence is rare, leading cause of death.
• Most types: leukemias, sarcomas, embryonic tumors.
• Originates often from mesodermal germ layer (connective tissues, bone, cartilage, muscle, blood).
• Often diagnosed during peak growth, fast-growing tumors.
• Etiology*
• Genetic Factors: chromosome abnormalities (aneuploidy, amplifications, deletions, translocations), Wilms tumor, urogenital abnormalities, Down syndrome, Fanconi anemia, Bloom's syndrome, oncogenes and tumor-suppressor genes
• Environmental Factors: prenatal exposure to medications/ionizing radiation, childhood exposure to medications, electromagnetic fields, viruses, anabolic androgenic steroids, cytotoxic agents, immunosuppressive agents, Epstein-Barr virus, AIDS.
• Specific Cancers (examples)
• Nephroblastoma (Wilms Tumor):*
• Malignant renal/intra-abdominal tumor
• Diagnosis: hx & physical exam, congenital anomalies, family hx of cancer, signs of malignancy, abdominal ultrasound/CT, urine/serum analysis, hematological studies.
• Osteosarcoma:*
• Malignant bone tumor (10-25 years old)
• Diagnosis: X-ray, CT scan, MRI, biopsy
• Manifestations: pain at affected site, soft tissue mass, limping.
• Leukemia:*
• Cancer of the blood (pathphysiology is unknown), unrestricted proliferation of immature WBCs.
• Acute leukemia: rapid disease progression, short survival
• Chronic leukemia: gradual onset, longer survival
• Subjective symptoms: fatigue, infections, bleeding tendencies
• Objective symptoms: anemia, weight loss, organ enlargement

Additional Topics (from the presented slides)

Test your knowledge on the differences in cancer prevalence and risk factors between children and adults. This quiz explores the unique challenges faced in cancer detection and the types of cancer that predominantly affect adolescents. Gain insights into the field of cancer epidemiology and its distinctions from general health studies.