LO Flashcards
Name three types of interstitial lung disease.
▪ Hypersensitivity Pneumonitis
▪ Sarcoidosis
▪ Cell mediated
▪ US black>white
▪ Granulomas
▪ Hilar lymphadenopathy (On chest X-ray)
▪ Raised angiotensin converting enzyme (Biomarker used for diagnosis)
▪ Involves the lungs but this is a systemic disease
▪ Idiopathic Pulmonary fibrosis
▪ A group of condition called IPF
▪ Lower part of the lungs is lost and becomes scarred and become fibrous tissue
▪ Sometimes it is part of systemic disease
▪ Once established, prognosis is like lung cancer
▪ Pattern on chest x-ray look like honeycomb
There are several types of interstitial lung disease. One is Hypersensitivity pneumonitis (extrinsic allergic alveolitis). Describe the immune response behind this condition. And how it presents.
▪ Type III (immunocomplex formation) and type iv (cell mediated)
▪ Antigen that instigates this reaction is antigen present in bird fancier (from bird feathers) or in grain (farmer’s lung)
▪ Presents as an acute illness (SOB due to inability for proper gas exchange due to inflammation around the bronchi which reduces diameter, and thickening of alveoli which affects efficient gas exchange)
Lung cancer can be Benign, primary malignant, or secondary malignant. Explain.
Benign e.g. mesenchymal
Primary malignant
▪ The conversion of cells from one type of mature cell to another type of mature cell = metaplasia (In lungs due to noxious stimulus from pseudo columnar of the epithelium to squamous )
▪ Secondary genetic changes after metaplasia which cause progressive disordered proliferation and maturation = dysplasia
▪ When there is invasive it becomes malignant
▪ Carcinomas = malignant epithelium tumors
Secondary Malignant
▪ Secondary cancer in lungs is common
▪ Usually not the presenting feature - usually have major problems else where by this point
▪ Sarcoma spread by blood, so is renal carcinoma and lymphoma
▪ Sometimes patient present with renal carcinoma through an X-ray showing canon/snooker balls on the scan
List primary epithelial types of cancer.
▪ Squamous (40%) (some times called non-small cell lung cancer (NSCLC)) ▪ Common ▪ History of smoking ▪ Air pollution ▪ Asbestos ▪ Fibrosing lung disease ▪ TNM staging
▪ Adenocarcinoma (from granular) also NSCLC
▪ Also common 40%
▪ Associated with smoking
▪ Lung scar (sometimes if you have had tuberculosis and had a scar you will develop cancer in that scar)
▪ Asbestos
▪ Adenocarcinoma - bronchoalveolar (cancer cell replace alveolar cell)
▪ Variant of adenocarcinoma
▪ Pattern of spread - intrapulmonary dissemination (you cough the cells up then aspirate them making them spread around the lungs)
▪ Small cell undifferentiated (from primitive neuro endocrine cells - not doing very much but with some function taken up and producing amines and various mediators - they are undifferentiated, they can grow very rapidly, and can cause death very rapidly - initially they respond well to chemotherapy however)
▪ Tend to be neuroendocrine
▪ Has paraneoplastic effects
▪ Neurological - e.g. demyelination
What is meant by paraneoplastic syndromes?
▪ Series of symptoms caused by the tumor, but not directly due to its presence, it is due to immunological response that is caused by substances produced by the tumor - this can affect any of the bodies systems. For example, clubbing is a symptom of paraneoplastic syndrome
▪ It is due to what the tumor produces l
▪ For example:
▪ Bioactive amines or peptides
○ ADH - so you cannot produce urine
○ PTN-Like peptides - causes release of calcium
○ ACTH - causing adrenal hyperplasia but also pigmentation
What is a common paraneoplastic syndrome in Squamous Cell Carcinoma (NSCLC)?
- Humoural Hypercalcaemia
- Tx ; Fluids, Bisphosphnates
What is a common Paraneoplastic syndrome in small cell carcinoma?
- SIADH
Name the malignancy of the pleura.
Describe main features of mesothelioma.
What is the benign equivalent of mesothelioma?
Name the malignancy of the pleura.
- Mesothelioma (malignancy arising from the lining cells of the pleura - grows along the pleura - )
Describe main features of mesothelioma. ▪ Almost always associated with asbestos ▪ Incidence is rising ▪ Long lag period: 20-40 years ▪ Male: Females 5:1 - reflects industrial exposure to asbestos)
What is the benign equivalent of mesothelioma?
▪ Fibrous pleural plaques (may ship yard worker who do not develop mesothelioma develop fibrous plaques)
Anti-B and Anti-A are which immunoglobulin?
IgM
If you are blood group O, what antibodies do you have?
- Anti A and Anti B
AB = No naturally occurring antibodies
Individuals who are Rhesus negative and receive Rhesus positive blood will produce which immunoglobulin?
IgG
Which reaction is more dangerous in terms of haemolysis?
- IgM (as it rapidly activates complement system leading to immunocomplexes which destroy the red blood cells) however in IgG Fc Receptors on macrophages will bind IgG-coated red blood cells then gradually destroy them
Cause, presentation, and management of transfusion reactions
Acute hemolytic Reactions
Symptoms: back pain, jaundice, dark urine, chills, fainting or dizziness, fever, flank pain, skin flushing
Management: stop transfusions, the rest depends on the severity of the reaction (symptom management, or ABC resuscitation)
Delayed Hemolytic Reactions (Manifests 2-14 days after transfusion of RBC component)
Symptoms: similar to acute reaction but less severe
Management: most have benign course and require no treatment
Urticaria (over the chest or abdomen, mild – treat with hydrocortisone) or anaphylaxis (Allergic reaction)
Febrile Proteins (Non-haemolytic - Reaction caused by antibodies against donor plasma protein/antigens on contaminating white blood cells (leukocytes and HLA antigens) – rare as all white blood cells in donated blood are now depleted Symptoms: fever and chills during transfusion
Define a biomarker.
A tumour marker is anything present in or produced by cancer cells or other cells of the body in response to cancer that provides info about the cancer
Due to insufficient sensitivity and specificity (Which are limitations of tumor biomarkers), tumour marker are not well equipped to spot tumours. Based on this, define the role of tumour biomarkers.
They are extremely useful for determining whether a tumour is responding to treatment or assessing whether it has recurred
Name the two types of tumour markers.
Circulating tumour markers (in blood, urine, stool, bodily fluids)
• Estimate prognosis
• Detect any cancer after treatment
• Assess response to Tx
• Monitor whether cancer can become resistant to Tx
Tissue tumour markers (In the sample taken by biopsy)
• Stage and/or classify cancer
• Estimate prognosis
• Select appropriate treatment (targeted therapy)
State the difference between prognostic and predictive biomarkers.
Prognostic marker used to estimate the course and severity of the disease which is better for population level, while predictive is to predict whether treatment will be effective which is better suited on an individual level.
Give biomarker examples for colorectal, lung and renal cancer.
Colorectal
• CEA (Carcinoembryonic antigen) (elevated preoperative CEA levels in resectable colorectal cancer is associated with poor prognosis)
• RAS gene mutations - presence of this indicates the lack of response to certain therapy
Lung (NSCLC)
• EGFR mutation analysis - looking for activating mutations in EGFR where there is abnormal hyperactive signaling - USE drug called erlotinib
• KRAS mutation analysis - activating mutations too - here erlotinib wont work but they will receive some other therapy
* ALK (Anaplastic Lymphoma Kinase) rearrangement analysis - this is found in 4% of patients with NSCLC (due to deletion or translocation leading to formation of fusion protein). This is mutually exclusive with EGFR and KRAS mutations * PD-L1 - this biomarker is used when you want to decide which check point inhibitor to use
Renal Cancer - No current approved markers, but some are being studied
But there is some anti-PD-L1 drugs which block the PD-L1 receptor on the T cells which the tumor cells usually bind to make sure they are not attacked by immune system. This way the immune system begins to recognize the tumor cells again.
Appreciate the evolving treatment of lung cancer
- Conventional chemotherapy - good for small undifferentiated
- Targeted, small molecule - good for squamous and adeno
- Immuno-oncology and check point inhibitors - antibodies which inhibit check points, these check points usually allow immune cells (like T cells) to recognize tumor cells as own cells and not attack them. Inhibiting these check points (e.g. PD1 inhibition allows the immune cells of the body to destroy tumor cell in some instances
PD-L1 levels (a biomarker) can be used to decide which check point inhibitor to use against certain lung cancers.
A) What would you use in a Squamous Cell NSCLC with PD-L1 levels <50%
B) >50%?
A)
- Anti-PD1, carboplatin and paclitaxel
B)
- Anti-PD-1
List where you would find tumour markers.
▪ Blood ▪ Urine ▪ Stool ▪ Tumours ▪ Other tissue or bodily fluids (Note: genomic markers such as tumour gene mutations and patterns of tumour gene expression are being used as tumour markers now)
Describe the clinical features and initial management of Malignant Spinal Cord Compression .
Oncological Emergency
A) Presentation:
- Neurological symptoms such as paralysis, paresis (muscular weakness caused by nerve damage), loss of sensation, and incontinence, and also pain
B) Management:
- Commece dexamethasone immediately if you suspect it (16mg OD then continue 8mg OD)
- Then other scans can be
- then irradiation can be done (radiotherapy within 6-24 hrs = good chance of remission)
If it takes longer than 72< hrs to get a person with Malignant Spinal Cord Compression to radiotherapy what are the implications on recovery?
- they can maintain present state
- you stop the situation from getting worse
- remission of symptoms no longer likely
Explain Vena Cava Superior Syndrome.
▪ Group of symptoms caused by the obstruction of the superior vena cava
▪ Sx: swelling of face/neck/upper body/arms, SOB, and Coughing
- Irradiation therapy same day!!
Explain Total or large partial atelektasis.
▪ Atelectasis = collapse or incomplete expansion of lung parenchyma
- Irradiation therapy same day!
