Patho - Cancer Manifestations, Progressions, Diagnoses and Childhood cancer

Cancer risk factors are often categorized as?

Modifiable or non-modifiable, or environmental (may or may not be individually modifiable)

What is a modifiable cancer risk factor?

Lifestyle habits or environmental exposures you can alter to lower risk

What is a non-modifiable cancer risk factor?

Inherent traits or biological factors you can’t change

What are some examples of modifiable risk factors?

Chronic inflammation, Nutrition/Weight, Lifestyle/Substances, Tobacco Use

How is chronic inflammation a modifiable risk factor for cancer?

Chronic inflammation predisposes a person to cancer

• In chronic inflammation, the body is constantly trying to repair areas that are inflamed, including cancer cells

• Inflammatory would-healing response pronites cellular proliferation and angiogenesis

• Inflammation also predisposes cells to dysplastic (abnormal) changes

What is the most important risk factor for cancer?

Tobacco use

What are son non-modifiable risk factors of cancer?

• Aging - genetic mutations in body cells increase with age

  • age-related cellular changes due to cumulative stress/exposures

  • more errors in replication of cellular DNA during mitosis

• Heredity

  • shared genes or environments within families increase risk

  • inherited oncogenes raise predisposition for cancer

  • protective genes may become silenced via epigenetic modifications

What are some environmental risk factors of cancer?

• Ionizing radiation

  • includes exposure to x-rays and other radioactive sources

  • randomly damages tissues, cells, and chromosomes

  • thyroid cancers, leukemias, lymphomas often result from ionizing radiation

• Ultraviolet radiation

  • principle source is sunlight and artificial tanning beds

  • can lead to basal cell carcinoma, squamous cell carcinoma, and melanoma

What is the most common symptom of cancer?

Fatigue

Pain may correlate with the stage of cancer. What is pain?

Whatever the experiencing person says it is

• can be influenced by fear, anxiety, sleep loss

• Mechanisms include pressure, obstruction, invasion of sensitive structures, tissue destruction

What is syndrome of cachexia?

Leads to protein-calorie malnutrition and progressive muscle wasting and unintended weight loss (another common symptom of cancer)

What is the physiology of cachexia?

• Higher basal metabolic rate because cancer cells utilize any calories they can to feed angiogenesis process — results in less nutrition to rest of body

• Shift of energy use from body growth/repair to tumor growth

What are the signs/symptoms of cachexia?

• Altered metabolic labs

• Fatigue/loss of appetite/altered taste

What are some hematologic changes associated with cancer?

• Anemia/red blood cell count — can be caused by treatment related side effects

  • chronic bleeding neear tumor sites

  • malnutrition - nutrients needed for red blood formation not absorbed

  • medical therapies

  • malignancy in blood-forming organs

• Leukopenia and thrombocytopenia

  • direct tumor invasion to the bone marrow

  • chemotherapy drugs that are toxic to the bone marrow

• Infection/White blood cell count

  • high or low WBC can signal cancer, result from cancer treatment, or reflect common infection

  • risk of cancer increases when the absolute neutrophil and lymphocyte counts fall

What are paraneoplastic syndromes?

Rare group of disorders that develop when a tumor triggers an abnormal immune response OR releases hormones/chemical signals that affect distant, healthy organs

• May be the earliest symptom of an unkonwn cancer and are often life-threatening

• Effects are not explained by the presence of the tumor, rather an indirect effect

What is the significance of paraneoplastic syndromes?

• May be the earliest symptom of an unknown cancer

• May represent serious and life threatening problems

• They may mimic progression; therefore interfering with appropriate treatment

What is direct invasion (local spread)?

When a tumor directly invades neighboring tissues

Direct invasion occurs in what 3 ways?

• Cellular replication

• Release of lytic enzymes (protease)

• Vessel transport

Describe cellular replication, a type of direct invasion.

As cancer cells continue to replicate, they spread out and pile on each other. This constant increase in tumor size displaces/stretches surrounding tissue/

• Mechanical pressure causes invasion of neighboring tissues

• There is also displacement of healthy tissue and organs

Describe release of lytic enzymes (protease), a type of direct invasion

These enzymes degrade the extracellular matrix of normal tissues, making it easier for cancer cells to invade.

• Creates pathways for tumor cells to move

Describe vessel transport, a type of direct invasion

Cancer cells can move into local tissues using nearby blood or lymphatic vessels

• Involves intravasation and extravasation

• Vessel transport is involved in both direct invasion and is a key mechanism by which cancer metastasizes to distant organs

What is intravasation?

A type of vessel transport characterized by: Movement of cancer cells through the basement membrane layer of a tissue, into blood or lymphatic vessels of surrounding tissue

What is extravasation?

A type of vessel transport characterized by: Movement of cancer cells out of blood or lymphatic vessels, into surrounding tissue

What is metastasis?

Spread of cancer cells from site of origin to distant tissues and organs

• It is a complex process that involves locomotion, cancer cell survival (metastatic cells must be able to withstand physiological stress of travel through the blood and lymphatic circulation), and proliferation in distant locations

What is the most common pathway for metastais?

Through lymphatic vessels , then into the bloodstream

What is epithelial-mesenchymal transition (EMT)?

A normal process is human embryogenesis, but cancer cells use it to initiate the direct invasion metastatic cascade, where:

• adhesion to basement membranes is lost

• Migratory capacity increases

• and resistant to apoptosis develops

Is cancer metastasis random?

NO, cancer often metastasizes in predictable patterns

What is tropism?

The tendency of specific cancer cells to metastasize to certain organs rather than others

What is primary prevention?

Aims to stop a disease from ever starting (vaccines, smoking cessation)

What is secondary prevention?

Aims to detect early cancers before symptoms develop, allowing for prompt treatment W

What are the benefits of cancer screening?

Early detection allows for less invasive treatment options, prevents tumors by removing precancerous lesions, and saves lives

What are the risks of cancer screening?

False-positive or false-negative results (stressful), over-diagnosis of harmless growths, and complications from procedures

What is the combined approach to confirm and stage cancer?

• Physical exam/history - helps outline symptoms, lifestyle factors, and family risk assessment data

  • palpation, inspection to identify and size solid tumors

• Lab tests - provide data to measure body function and abnormality

  • blood/urine tests, tumor marker, hormone levels, antigen/antibody activity, genetic diagnosis

• Imaging - can identify solid tumors or organ-related changes

  • U/S, X-ray and Mammogram, CT scan, MRI, PET Scan

• Procedures - offer opportunity to sample tissues for patho examination or help visualize internal structure more closely

  • Histological sampling: biopsy, pathologic evaluation, genetic testing, bone marrow biopsy

  • Visualization: endoscopy, colonoscopy, exploratory laparotomy, spinal tap

What are tumor markers?

Substances found in the body that can indicate the presence of cancer and provide information about how cancer behaves

• Various hormones, proteins, enzymes, genetic mutations, antigens, antibodies

• Made by cancer cells or by normal cells in response to a tumor

How can you test for tumor markers?

Blood, urine, stool, CSF, or tissue samples

What are the clinical uses of tumor markers?

• Screening

• Diagnosis (rarely)

• Confirmation of diagnosis

• Staging

• Verify treatment effectiveness

• Monitoring of recurrence of cancer in survivors

How does chemotherapy work?

Use of nonselective cytotoxic drugs that target vital cellular machinery or metabolic pathways critical to both malignant and normal cell growth and replication

• it is a systemic therapy - not localized like radiation and surgery

• targets rapidly growing/dividing cells

What are some side effects of chemo?

Alopecia, nausea, vomiting, mucositis, diarrhea, bone marrow toxicity, neuropathy

How does radiation work?

Causes molecular damage to the cancer cell’s DNA

• Causes irreversible damage to tissues near the tumor and is used to kill cancer cells while trying to minimize damage to rest of body

• Goals:

  • eradicate cancer without excessive toxicity

  • Local control only

  • Decrease pain

  • Avoid damage to normal structures

What is brachytherapy?

Internal radiation therapy in which implants “seeds” contain a radiation source and are placed in the body in or near the tumor

• allows for high dose of radiation to tumor while reducing exposure to surrounding healthy tissues

• often used to treat cancers of head and neck

How can surgery be used as a cancer treatment?

• Tumor excision

• Tumor biopsy and lymph node sampling for purpose of staging cancer

• palliative -relief of symptoms

• Prevention - in selected high risk diseases, surgery plays role in prevention of cancer

What is immunotherapy?

A type of cancer treatment that uses artificial stimulation of the immune system to treat cancer

What is active immunotherapy

The body is stimulated to produce antibodies against specific cancer antigens

What is passive immunotherapy

Infusion of exogenous antibodies and lymphocytes specific to the patient’s cancer

What are some adverse effects to cancer treatment?

• Nausea - one of most common side effects

• Gastrointestinal toxicity

• Myelosuppresion - reduced bone marrow activity

What are the types of nausea experienced as an adverse effect to cancer treatment?

• Acute - directly related to treatment episode itself

• Delayed - days weeks after treatment

• Anticipatory - experiencing n/v in anticipation of treatment

Patient demographic affect likelihood

• younger pts

• females>males

• ETOH users less susceptible

What are some gastrointestinal effects of cancer treatment?

• Constipation

• Diarrhea

  • changes to mucosa

  • immune toxicity resulting in colitis

• Mucositis

• Hepatitis - usually seen with oral chemotherapeutic agents or immunotherapy

What are some myelosuppresion effects of cancer treatment?

• Anemia

  • blood transfusions used to restore

• Leukopenia and neutropenia

  • granulocyte colony-stimulating factor used to restore WBC

• Thrombocytopenia (low platelets)

  • transfusion for sig low platelets or spontaneous bleeding

Most childhood cancers originate from what germ layer?

Mesodermal germ layer

What genetic disorder may increase risk of cancer? What type of cancer?

Down syndrome may increase risk of leukemia

What is WGAR syndrome?

Syndrome in which 4 congenital abnormalities ar found together. Listed as a familial risk to cancer

• Wilms Tumor

• Aniridia

• Ambiguous Genitalia

• Mental Retardation

What are the most common cancers in children?

Brain, leukemia, and soft tissue