Session 9 Flashcards

1
Q

Risk factors for tuberculosis?

A

• Non-UK born/recent migrants – South Asia 54.8% – Sub-Saharan Africa 29.5% • HIV • Other immunocompromised conditions • Homeless • Drug users, prison • Close contacts • Young adults (also higher incidence in elderly)

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2
Q

Microbiology of tuberculosis?

A

Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex
7 closely related species  M tuberculosis  M bovis  M africanum

•Non-motile rod-shaped bacteria
•Obligate aerobe
•Long-chain fatty (mycolic) acids, complex waxes & glycolipids in cell wall Structural rigidity Staining characteristics Acid alcohol fast
•Relatively slow-growing compared to other bacteria
Generation time 15-20h

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3
Q

Transmission of TB

A

Spread is by respiratory droplets –coughing, sneezing etc
•Droplet nuclei •<10µm particles •Suspended in air •Reach lower airway
•Infectious dose 1-10 bacilli
•Contagious, but not easy to acquire infection Prolong exposure facilitates transmission (at-least 8 hours / day upto 6 months)

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4
Q

Pathogenesis of TB

A

slide 15 lec 1

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5
Q

Two forms of infection for TB

A

Clinical infection (TB)
Subclinical infection (LTBI)
90% of infection is latent infection Reservoir of potential disease
Progression risk is heterogeneous Highest risk with recent infection
First two years: 5% Rest of life time: 5% Total: 10%

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6
Q

TB vs LTBI

A

slide 17 lec 1

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7
Q

Primary TB

A

– Ghon focus/complex – Limited by CMI – Usually asymptomatic – Rare allergic reactions include Erythema nodosum – Occasionally symptomatic & can also disseminate - i.e. miliary & extra pulmonary
Post-primary TB
• Reactivation or exogenous re-infection • >5 years after primary infection • 5-10% risk per lifetime
• Clinical presentation – Pulmonary or extra-pulmonary

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8
Q

Risk factors for Reactivation

A
• Infection with HIV
• Substance abuse 
• Prolonged therapy with corticosteroids • other immunosuppressive therapy, 
• tumor necrosis factoralpha [TNF-α] antagonists
• Organ transplant
• Haematological malignancy
• Severe kidney disease /haemodialysis
• Diabetes mellitus
• Silicosis
• Low body weight 
Risk factors for Reactivation
All suspected and confirmed cases of TB must have a HIV test
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9
Q

Sites of TB Disease table

A

slide 21 lec 1

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10
Q

Pathology of TB

A

Caseating granulomata – Lung parenchyma – Mediastinal LNs

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11
Q

When to suspect TB

A

• Non-UK born/recent migrants - Recent arrival or travel • HIV • Other immunocompromise states (i.e. cancers) • Homeless • Drug users, prison inmates • Close contacts of patients with TB • Specific clinical features: Unexplained Fever, weight loss, Malaise, Anorexia

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12
Q

signs and symptoms of pulmonary TB

A

Symptoms
• Fever • Night sweats • Weight loss and anorexia • Tiredness and malaise
• Cough (most common) • Haemoptysis occasionally • Breathlessness if pleural effusion
Signs on examination
• Often no chest signs despite CXR abnormality • Maybe crackles in affected area • In extensive disease: – signs of cavitation, – fibrosis • If pleural involvement: typical signs of effusion

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13
Q

Investigations of Pulmonary TB

A
  • Chest X Ray
  • Sputum – 3 early morning samples minimum volume 5ml
  • Induced Sputum
  • Bronchoscopy (patients with a dry cough)
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14
Q

Radiology for TB

A

Pulmonary TB • Apex of the lung often involved as more oxygen there •Ill Pulmonary TB • Apex of the lung often involved •Ill defined patchy consolidation •Cavitation usually develops within consolidation •Healing results in fibrosis
Pleural TB- Pleural effusion defined patchy consolidation •Cavitation usually develops within consolidation •Healing results in fibrosis
Pleural TB- Pleural effusion

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15
Q

TB Microscopy

A

Remains the mainstay of TB Diagnostics Worldwide
Rapid test, cheap test Sensitivity is approximately 5x103AFB/ml of sputum
60% -70% of culture positive samples are microscopy positive
Indicates infectiousness ‘Smear positive case’
Cannot differentiate MTB from NTM
Cannot differentiate live and dead organisms

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16
Q

TB Culture

A

• Remains the Gold standard for TB diagnostics • One of the most sensitive methods for detecting Mycobacteria • Solid & liquid culture systems • Has improved with automated culture technology • Allows identification and susceptibility testing

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17
Q

Additional tests – Nucleic Acid Amplification Tests (NAAT) for TB

A
  • Role of NAAT for primary samples? – Rapid diagnosis of smear +ve – Drug resistance mutations
  • Whole genome sequencing (WGS)
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18
Q

Histology of TB

A

tuberculosis granuloma, caseous necrosis - cheese like

19
Q

Tuberculin sensitivity Test (TST

A
Oldest diagnostic      tests in use (1890) Measures CMI, in the form of DTH to PPD of M tuberculosis Tuberculin injected intradermally The induration is read 48-72 hrs later
Tuberculin Skin Testing
Read 2-3 days later Subjective interpretation
False positives (BCG, non TB ) False negatives (immunocompromised i.e HIV/ drugs/ advanced disease etc
Cheap (???) Laboratory infrastructure not required Evidence to support ability to predict active disease in those that are latently infected
20
Q

Interferon Gamma Assays for TB

A

• In-vitro test • T cell based assay • Measures Interferon Gamma (IFNg assay)
slide 34
Interferon Gamma Releasing Assays (IGRAs) •Detection of antigenspecific IFN-gamma production •T Spot TB •Quantiferon Gold •No cross-reaction with BCG •Cannot distinguish latent & active TB •Similar problems with sensitivity & specificity

21
Q

Anti-TB drugs and TB treatment

A

First line medications
•Rifampicin •Isoniazid •Pyrazinamide •Ethambutol
Second line medications
•Quinolones (Moxifloxacin)
•Injectables •Capreomycin, kanamycin, amikacin •Ethionamide/Prothionamide •Cycloserine •PAS •Linezolid •Clofazamine

TB treatment
• Early and adequate treatment with Anti TB Drugs • Close monitoring of compliance • Makes the patient Non infectious • No secondary transmission and cases
• Multi-drug therapy
– Rifampicin • Raised transaminases & induces cytochrome P450 • Orange secretions / urine – Isoniazid • Peripheral neuropathy (pyridoxine 10mg od) • Hepatotoxicity – Pyrazinamide • Hepatotoxicity – Ethambutol • Visual disturbance • Vitamin D • Surgery
• Duration – 3 or 4 drugs for 2/12 – Then Rifampicin & Isoniazid 4/12 – 18/12 if CNS TB – Cure rate 90%
• Adherence – Directly observed therapy (DOT) – Video observed therapy (VOT)

22
Q

Development and spread of drug resistance

A

Natural history – during multiplication small number of naturally drug resistant organisms arise through spontaneous mutations
Improper drug regimens / poor drug compliance leads to selection of these mutants
Single and multi drug resistance
Diagnostic delays, overcrowding and inadequate infection control facilitates transmission of drug resistance

23
Q

MDR & XDR TB

A

• Multi-drug resistant TB (MDR) – Resistant to rifampicin & isoniazid • Extremely drug-resistant TB (XDR) – Also resistant to fluoroquinolones & at least 1 injectable • Spontaneous mutation + inadequate treatment • Likelihood increased – Previous TB Rx – HIV+ – Known contact of MDR TB – Failure to respond to conventional Rx – >4 months smear +ve/>5 months culture +ve • 4 to 5 drug regimen, longer duration – Quinolones, aminoglycosides, PAS, cycloserine, ethionamide,

24
Q

Miliary tuberculosis

A
  • Milia (latin) = seed • Bacilli spreading through the blood stream – widespread infection • Either during primary infection or during reactivation • Lungs are always involved – but few respiratory symptoms – Fever, very unwell, dry cough,
  • Often multiple organs involved • Other organ involvement variable – Headaches suggest meningeal involvement – Pericardial, pleural effusions small – Ascites may be present – Retinal involvement (choroid tubercles seen)
25
Q

Extra-pulmonary TB

A
  • Lymphadenitis • Scrofula • Cervical LNs most commonly • Abscesses & sinuses
  • Gastrointestinal • Swallowing of tubercles • Peritoneal • Ascitic or adhesive • Genitourinary • Slow progression to renal disease • Subsequent spreading to lower urinary tract
  • Bone & joint Haematogenous spread Spinal TB most common Pott’s disease
  • Tuberculous meningitis Chronic headache, fevers CSF – markedly raised proteins, lymphocytosis
26
Q

Prevention of Tuberculosis

A

Notifiable Disease All forms of tuberculosis are compulsorily notifiable under the Public Health Act 1984 • The doctor making or suspecting the diagnosis is legally responsible for notification. • A decision to commence treatment (but not chemoprophylaxis) indicates a level of suspicion which should trigger notification for all forms of tuberculosis

Notification….
Triggers contact tracing procedures
Provide surveillance data to detect outbreaks and monitor epidemiological trends
Active case finding of symptomatic patients – new and secondary case finding

27
Q

Control of TB

A
  • Treatment of index case Detection and treatment of cases and contacts
  • Prevention of transmission – Personal protective equipment – Negative pressure isolation
  • Reduce susceptible contacts – Address risk factors – Vaccination
28
Q

BCG

A

Bacille Calmette-Guerin (BCG): live attenuated M. bovis strain Given to babies in high prevalence communities only (since 2005) 70-80% effectiveness in preventing severe childhood TB Protection wanes Little evidence in adults
• Not part of the routine childhood vaccination schedule only given to neonates / infants / older children thought to have an increased risk of coming into contact with TB. • Other indications – • new entrants from high risk areas • health workers • close contacts of active respiratory TB • Other groups –Ref Green Book
• Always consider HIV testing where appropriate before giving BCG

29
Q

Epidemiology of lung cancer

A
  • Highest cancer related deaths world wide
  • 35,000 deaths per year – UK
  • 500 deaths per year- Leicester
30
Q

Lung Cancer and smoking

A

Smoking causes: • ~90% of lung cancer deaths in men • ~80% of lung cancer deaths in women • ~20% of lung cancer cases in non smokers • One Third of all cancer deaths 35-year old male who smokes 25 cigarettes per day: • 1 in 7 risk of dying from lung cancer before age 75 • 1 in 10 risk of dying from coronary disease • Almost 1 in 2 risk of dying prematurely from smoking-related disease

31
Q

Lung Cancer: Risk factors other than smoking

A

• Asbestos (?~1000 deaths/ year • Radon (from mining or indoor exposure) ~ 1500 deaths / year • Other “occupational carcinogens” – chromium, nickel, arsenic • Genetic/familial factors (relative risk ~ 1.6) • Around 5000 cases a year in never smokers

32
Q

Screening for lung cancer

A

• Disease with serious consequences • High prevalence of detectable disease • Test detects little pseudo-disease (overdiagnosis) • Test detects disease before the critical point • Test causes little morbidity • Test affordable and available • Treatment exists • Treatment more effective when applied before symptomatic detection • Treatment not too risky or toxic
 IN DISEASE SPECIFIC MORTALITY

33
Q

Staging for cancer

A

USE panopto

34
Q

Common site of spread for lung cancer?

A

Brain, draining lymph nodes, pericardium, other rlung, pleura, liver, adrenals, bones

35
Q

Staging tests for lung cancer

A

• Imaging
CXR CT scan Pet Scan MRI USS Bone scan ECHO

CXR CT scan Pet Scan MRI USS Bone scan ECHO
• Tissue sampling
Bronchoscopy - Endobrochial Bx, wash, EBUS, radial EBUS, EUS
USS - neck node, lung/chest wall mass, pleural fluid, liver
CT biopsy - lung, pleura
Thorocoscopy - medical
Surgical - mediastinoscopy, VATS pleural bx, rigid bronchoscopy, neck and axillary nodal excision, VATS excision bx, adrenal bx, brain bx, bone bx

36
Q

Lung cancer: symptoms

A

Primary tumour • Cough • Dyspnoea • Wheezing • Haemoptysis • Lung infection • Chest / shoulder pain • Weight Loss • Lethargy/Malaise
• NO SYMPTOMS
Regional metastases • Bloated face (SVC obstruction) • Hoarseness (left recurrent laryngeal nerve palsy) • Dyspnoea (anaemia, pleural or pericardial effusions) • Dysphagia (oesophageal compression)
• Chest pain (parietal pleural involvement)
Distant metastases
• Bone pain/fractures
• CNS symptoms (headache, double vision, confusion etc.)
Metabolic
• Thirst (hypercalcaemia) • Constipation (hypercalcaemia) • Seizures (hyponatraemia – SIADH, small cell)

37
Q

Signs of lung cancer

A

• Cachexia • Pale conjunctiva • Cervical lymphadenopathy • Horners Syndrome • Consolidation • Superior Vena Cava obstruction • Signs of pleural effusion • Muffled heart sounds • Liver enlargement • Skin metastases • Neurological long tract signs • NO SIGNS
Finger clubbing

38
Q

Lung cancer: paraneoplastic syndromes

A

Endocrine - Hypercalcaemia - Cushing’s syndrome - Inappropriate Antidiuretic HoHormone Secretion (SIADH) Sec
Neurological - Encephalopathy - Peripheral neuropathy - Eaton-Lambert syndrome
- Pancoast syndrome
Haematological - Anaemia - Thrombocytosis
Cutaneous - Dermatomyositis
Skeletal - Finger Clubbing

39
Q

Imaging used for lung cancer?

A

All Chest Xray Staging chest CT
Some:
PET-CT Head CT Pelvic CT MRI -various Bone Scan Ultrasound

40
Q

Biopsy for lung cancer

A

No Biopsy or one or more of the following:
•Bronchoscopy – standard or with endobronchail ultrasound (EBUS) •Cervical lymph node fine needle aspiration (FNA) •Pleural fluid aspiration (thorocentesis) •CT guided lung biopsy •CT guided pleural biopsy •CT/USS guided liver biopsy •Adrenal biopsy •Skin biopsy •Bone biopsy •Brain biopsy •Lymph node biopsies (axillary, abdominal)

41
Q

Pathology of Lung Cancer

A

Carcinoma is an invasive malignant epithelial tumour
Main types are: Non-Small Cell Lung Cancer: •Squamous cell carcinoma ~ 40% •Adenocarcinoma ~ 35% •Large Cell Carcinoma ~ 5% Small Cell Carcinoma ~ 12% Rare tumours (e.g. carcinoid) ~ 5%

• What are the molecular markers?
EGFR mutations ALK mutation KRAS mutations PD1 mutations PDL1mutations

42
Q

Survival by stage (non-small cell lung cancer)

A

slide 43 use panopto

43
Q

Multidisciplinary meeting (MDT) and performance status

A

slide 43
0 No symptoms, normal activity level 1 Symptomatic , but able to carry out normal daily activities 2 Symptomatic; in bed or chair less than half the day. Needs some assistance with daily activities 3 Symptomatic; in bed or chair more than half the day.
4 Bedridden 5 Dead

44
Q

Lung Cancer: Treatment overview

A
  • Surgery – Mostly for Non-Small Cell (20-25% operable). The best chance of cure
  • Radiotherapy – ‘Radical’ - with curative intent (includes stereotactic RT) – ‘Palliative’ - symptom control
  • Combination chemotherapy – Small Cell - potentially curative in a minority – Non-Small Cell - modest survival increase, symptom control – ‘Neoadjuvant’ therapy- chemo before surgery (to ‘downstage’ the tumour to allow subsequent surgery)) – ‘Adjuvant’- chemo after surgery (no benefit if < stage 2)
  • Combination Therapy – Combination chemo-radiotherapy – potentially curative
  • Biologic and immunotherapies - Based on mutational analysis - EGFR, ALK, RAS (Biologics), PD1, PDL1 (immunotherapy)
  • Palliative Care & other treatment - Active symptom control eg analgesia, radiotherapy, airway stents, anxiolytics, nutritional support, patient support groups. Treatment of tobacco addiction, coronary heart disease and other conditions