Cancer Flashcards

1
Q

Referral recommendation for skin lesion suspected of a basal cell carcinoma?

A
  • consider routine referral
  • only 2ww (suspected ca referral) referral if concern that delay may have impact eg. due to factors such as site or size
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2
Q

When to refer pt using suspected ca pathway referral (appointment within 2w) for melanoma?

A

1) suspicious pigmented skin lesion with weighted 7 point checklist score of 3 or more

or

2) dermoscopy suggests melanoma

3) pigmented or non-pigmented lesion that suggests nodular melanoma

4) suspected SCC

5) BCC but concern that delay will have signif impact eg. due to size or site

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3
Q

Pigmented lesion on the skin?

A

?melanoma

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4
Q

Can get what type of melanomas rarely?

A

nodular and amelanotic

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5
Q

What checklist is used to assess pigmented skin lesions?

A

7-point checklist

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6
Q

Melanoma may present when?

A

after spread to regional lymph nodes or wider mets

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7
Q

Main method to diagnose melanoma?

A

excision biopsy in secondary care

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8
Q

Raised lesion on skin?

A

?SCC

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9
Q

Diagnose SCC?

A

possible to visually but confirm by excision biopsy

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10
Q

Ulcer with raised rolled edge; prominent fine blood vessels around a lesion or nodule on the skin (pearly or waxy)?

A

Basal cell carcinoma

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11
Q

Diagnosis of BCC?

A

possible visually but confirm by excision biopsy

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12
Q

7-point checklist for suspected melanoma?

A

Major (2 points each):
- change in size
- irregular shape
- irregular colour

Minor (1 each):
- largest diameter 7mm+
- inflam
- oozing
- change in sensation

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13
Q

Most common type of ca in Western world?

A

BCC

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14
Q

BCC characteristics?

A
  • lesions also called Rodent ulcers
  • slow growth
  • local invasion
  • mets v rare
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15
Q

Most common type of BCC?

A

nodular

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16
Q

Nodular BCC?

A
  • sun exposed sites eg. head, neck
  • initially= pearly, flesh coloured papule with telangiectasia
  • later= ulcerate leaving central crater
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17
Q

Mx options for BCC?

A
  • surgical removal
  • curettage
  • cryotherapy
  • topical cream= imiquimod, fluorouracil
  • radiotherapy
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18
Q

Bladder ca commonly affects who?

A

males 50-80yrs

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19
Q

RFs for bladder ca?

A
  • male
  • current or previous (within 20yrs) smokers
  • exposure to hydrocarbons eg. 2-Napthylamine
  • chronic bladder inflam from Schistosomiasis infection= SCC
    -rubber manufacture
  • cyclophosphamide
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20
Q

Exposure to hydrocarbons eg. benzidine or 2-Naphthylamine from exposure to aniline dyes (eg. working in printing and textile industry) increases the risk of what?

A

bladder ca

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21
Q

examples of benign tumours of the bladder? (uncommon)

A
  • inverted urothelial papilloma
  • nephrogenic adenoma
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22
Q

Examples of bladder malignancies?

A
  • Urothelial (transitional cell) carcinoma (>90%)
  • SCC (1-7% expect is higher in regions affected by schistosomiasis- rare in UK)
  • Adenocarcinoma
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23
Q

Most common bladder malignancy?

A

urothelial (transitional cell) carcinoma (>90%)

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24
Q

Urothelial carcinomas may arise as what?

A

solitary lesions or may be multifocal causing ‘field change’ within the urothelium

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25
Growth pattern of urothelial carcinomas?
- 70% have papillary growth pattern= superficial and better prognosis - mixed papillary and solid growth or pure solid growth= more prone to local invasion and may be higher grade, worse prognosis
26
Those with T3 disease or worse in urothelial carcinoma have a 30%+ risk of what?
regional or distant lymph node metastasis
27
TNM staging for bladder cancer= T?
T0= No evidence of tumour Ta= Non invasive papillary carcinoma T1= Tumour invades sub epithelial connective tissue T2a= Tumor invades superficial muscularis propria (inner half) T2b= Tumor invades deep muscularis propria (outer half) T3= Tumour extends to perivesical fat T4= Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina T4a= Invasion of uterus, prostate or bowel T4b= Invasion of pelvic sidewall or abdominal wall
28
TNM staging of bladder cancer: N?
N1= Single regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node) N2= Multiple regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node metastasis) N3= Lymph node metastasis to the common iliac lymph nodes
29
Painless macroscopic haematuria?
?bladder ca
30
CP of bladder ca?
- painless marcoscopic haematuria - incidential microscopic haematuria= 10% females >50yrs found to have malignancy after infection excluded
31
Staging for bladder ca?
1) cystoscopy and biopsy or TURBT= histological diagnosis and depth of invasion 2) Pelvic MRI= locoregional spread 3) CT= distant disease 4) PET CT= nodes of uncertain significance
32
Tx for bladder ca?
superficial lesions= TURBT in isolation recurrences or higher grade/risk on histology= intravesical chemo T2 disease= surgery (radical cystectomy and ileal conduit) or radical radiotherapy
33
Prognosis of bladder ca?
T1 90% T2 60% T3 35% T4a 10-25% Any T, N1-N2 30%
34
How is cancer classified into types?
based on origin and characteristics of the abnormal cells
35
Carcinoma definition?
arises from epithelial cells that line internal organs and external surfaces
36
Types of carcinoma?
- adenocarcinoma - SCC - BCC - transitional cel carcinoma
37
Most common types of cancer?
carcinoma
38
Types of carcinoma: adenocarcinoma definition?
develops in glandular tissues eg. breast, prostate, colon, pancreas
39
Types of carcinoma: SCC definition?
found in squamous cells eg. skin or lining of organs, for example lungs, oesophagus
40
Types of carcinoma: BCC definition?
form of skin cancer that starts in the basal cells
41
Types of carcinoma: transitional cell carcinoma definition?
arises in lining of the bladder, ureters and renal pelvis
42
Sarcoma definition?
develops in connective or supportive tissues such as bone, muscle, fat, cartilage and blood vessels less common than carcinomas but more aggressive
43
Types of sarcoma?
- osteosarcoma - chondrosarcoma - liposarcoma - leiomyosarcoma
44
Types of sarcoma: osteosarcoma definition?
originates in bone
45
Types of sarcoma: chondrosarcoma definition?
arises in cartilage
46
Types of sarcoma: liposarcoma definition?
develops from fat tissue
47
Types of sarcoma: leiomyocarcoma definition?
develops in smooth muscle tissue
48
Leukemia definition?
cancers of the blood-forming tissues, incl. bone marrow and lymphatic system
49
Types of leukemia?
- Acute Lymphoblastic Leukemia (ALL) - Acute Myeloid Leukemia (AML) - Chronic Lymphocytic Leukemia (CLL) - Chronic Myeloid Leukemia (CML)
50
Types of leukemia: Acute Lymphoblastic Leukemia (ALL) definition?
affects lymphoid cells, common in children
51
Types of leukemia: Acute Acute Myeloid Leukemia (AML) definition?
affects myeloid cells, more common in adults
52
Types of leukemia: Chronic Lymphocytic Leukemia (CLL) definition?
slow-growing form affecting lymphoid cells
53
Types of leukemia: Chronic Myeloid Leukemia (CML) definition?
affects myeloid cells, progresses slowly
54
Lymphoma definition?
ca of the lymphatic system, which is part of the immune system relatively common, esp non-Hodgkin
55
Types of lymphoma?
- Hodgkin Lymphoma (Hodgkin's disease) - Non-Hodgkin Lymphoma (NHL)
56
Types of lymphoma: Hodgkin Lymphoma definition?
characterised by presence of Reed-Sternberg cells
57
Types of lymphoma: Non-Hodgkin Lymphoma definition?
diverse group of lymphomas that don't have Reed-Sternberg cells; including B-cell and T-cell lymphomas
58
Myeloma definition?
ca of plasma cells, type of WBC in bone marrow rare form of ca, affects mainly older adults
59
Type of myeloma?
multiple myeloma
60
Type of myeloma: multiple myeloma definition?
most common form, affecting many areas of body incl. bones and kidneys (Old CRAB)
61
Melanoma definition?
ca than originates in melanocytes, the cells that produce the pigment melanin in the skin less common than other skin ca (B/SCC) but more aggressive
62
Types of melanoma?
- cutaneous melanoma - ocular melanoma
63
Types of melanoma: cutaneous melanoma definition?
starts in skin
64
Types of melanoma: ocular melanoma?
rare form that starts in the eye
65
Central Nervous System (CNS) cancers definition?
ca that begin in brain or spinal cord can be mild or highly malignant, glioblastoma one of most severe
66
Common types of CNS cancers?
- glioblastoma - astrocytoma - meningioma
67
Types of CNS cancers: glioblastoma definition?
highly aggressive form of brain cancer
68
Types of CNS cancers: astrocytoma definition?
originates in star-shaped brain cells called astrocytes
69
Types of CNS cancers: meningioma definition?
affects meninges, the protective layers around brain and spinal cord
70
Germ Cell tumours definition?
arises from the cells that give rise to sperm or eggs (germ cells) most common in adolescents and young adults
71
Common locations of germ cell tumours?
usually develop in testes (testicular ca) or ovaries (ovarian germ cell tumours) but can form in other parts of body eg. brain
72
Neuroendocrine tumours definition?
arise from cells that release hormones into the blood in response to signals from NS rare and can be slow-growing, some can be aggressive
73
Types of neuroendocrine tumours?
- carcinoid tumours - pheochromocytoma
74
Types of neuroendocrine tumours: carcinoid tumours?
type of neuroendocrine tumour commonly found in GI tract and lungs
75
Types of neuroendocrine tumours: pheochromocytoma?
typically arises in adrenal glands
76
Blastoma definition?
typically arises in embryonic tissue or immature cells, usually seen in children
77
Common types of blastoma?
- retinoblastoma - neuroblastoma - hepatoblastoma
78
Common types of blastoma: retinoblastoma definition?
ca of the retina, typically in young children
79
Common types of blastoma: hepatoblastoma definition?
rare liver ca in children
80
Common types of blastoma: neuroblastoma definition?
starts in immature nerve cells, often in adrenal glands
81
Mesothelioma definition?
rare ca that affects lining of lungs, abdo or heart; often linked to asbestos exposure
82
Thyroid ca definition?
ca that forms in thyroid gland, with types like papillary, follicular, medullary and anaplastic thyroid ca
83
Types of cancers?
- carcinoma - sarcoma - leukemia - lymphoma - myeloma - melanoma - CNS ca - germ cell tumours - neuroendocrine tumours - blastoma - mesothelioma - thyroid cancer
84
What is the TNM staging used for?
to classify and describe details about the ca size, location and degree of spread, helps in planning treatment and estimating prognosis primarily for solid tumours eg. breast, lung, colon
85
TNM staging: what is T?
Tumour size and extent of the primary tumour
86
TNM staging: what is N?
Nodes indicates whether the cancer has spread to nearby lymph nodes (local spread)
87
TNM staging: what is M?
Metastasis refers to whether the ca has spread (metastasised) to distant organs or tissues (distant spread)
88
What would Tx, Nx or Mx mean in TNM staging?
can't be assessed
89
Cancer stage grouping?
use TNM to combine into overall stage grouping: stage I, II, III or IV some may have substage eg. IA or IIB depending on additional factors eg. tumour grade or specific molecular markers
90
Cancer stages?
0= cancer in situ (localised and not spread) I= small tumour, localised, without spread to lymph nodes II= large tumour or has spread to nearby lymph nodes, but no distant mets III= more advanced local/regional spread to lymph nodes or nearby tissues, but no distant mets IV= metastatic ca- has spread to distant parts of the body
91
TNM staging: what if the difference between N and M if in N the ca is still spreading?
N= local or regional involvement within the lymphatic system M= ca has spread beyond original area and reached distant organs or tissues so N is not considered metastasis
92
Brain and CNS cancers typically affect who?
children and young people
93
Symptoms of brain and CNS cancers?
new onset seizures, headaches, nausea, drowsiness, visual change, personality change
94
Ix/Mx for brain and CNS cancers in adults?
urgent direct access of MRI of brain or CT if MRI contraindicated, within 2w, in adults with progressive, sub-acute loss of central neurological function
95
Ix/Mx for brain and CNS cancers in children/young people?
very urgent referral (within 48hrs) in children with newly abnormal cerebellar or other central neurological function
96
Most common intracranial tumours in adults?
brain metastases
97
What do brain mets signify?
advanced disease state with significant impact on morbidity and mortality
98
What primary cancers are most likely to metastasise to the brain?
Lung (40-50%) Breast (15-25%) Melanoma (5-20%) Renal (5-10%) Colorectal
99
Pathways of spread for brain mets?
- hematogenous spread (most common)= via arterial circulation - lymohatic (less common)= typically involves leptomeningeal carcinomatosis - direct extension (rare)= from head and neck cancers
100
CP of brain mets?
- headache (worse in morning) - neuro deficit (eg. hemiparesis, aphasia) - seizures - cognitive and behavioural changes - symptoms of ICP= N&V, altered consciousness
101
Diagnosis of brain mets?
GOLD= MRI with contrast for number, size and location - Biopsy confirms in primary ca site is unknown or imaging inconclusive
102
Aim of Mx of brain mets?
controlling symptoms, reducing tumour burden and improving QOL
103
Mx for brain mets?
- supportive care - radiation therapy - systemic therapy - surgical resection
104
Mx for brain mets- supportive care?
- corticosteroids eg. dexamethasone= reduce peritumoral oedema and control symptoms eg. headache - anticonvulsants= seizures - palliative care for end-of-life
105
Mx for brain mets- radiation therapy, when is it used?
Whole Brain Radiotherapy (WBRT)= for multiple mets but associated with notable cognitive decline Stereotactic Radiosurgery (SRS)= if 1-3 mets; offers high dose radiation with minimal damage to surrounding tissues
106
Mx for brain mets: systemic therapy?
chemotherapy, targeted therapy or immunotherapy depending on primary tumour type and molecular characteristics used to better systemic control and penetration of blood brain barrier
107
Mx for brian mets: when is surgical resection indicated?
for accessible lesions causing signif mass effect or when histologic diagnosis required; improves neuro function and allows more effective adjuvant therapy
108
Prognosis of brain mets?
- generally poor but improving with targeted therapies and precision medicine - median survival ranges= several months to over a yr - depends on Tx and tumour biology
109
What drug class in tamoxifen?
selective oestrogen receptor modulator (SERM)= acts as an oestrogen receptor antagonist and partial agonist
110
Drug used in the Mx of oestrogen receptor positive breast ca?
tamoxifen
111
Adverse effects of tamoxifen (SERM)?
- vaginal bleeding, amenorrhoea - hot flushes (3% stop taking due to this) - VTE - endometrial ca
112
What drug class are anastrozole and letrozole?
aromatase inhibitors= reduces peripheral oestrogen synthesis
113
Drug used in the Mx of ER +ve breast ca in postmenopausal women?
Anastrozole
114
Why is anastrozole used for ER +ve breast ca in postmenopausal women?
it is an aromatase inhibitor that reduces peripheral oestrogen synthesis; important as aromatisation accounts for majority of oestrogen production in postmenopausal women
115
Adverse effects of anastrozole (aromatase inhibitor)?
- osteoporosis (DEXA scan) - hot flushes - arthralgia, myalgia - insomnia
116
What should be done when initiating pt on aromatase inhibitors for breast ca?
DEXA scan due to risk of osteoporosis
117
Malignant breast lump is usually what?
painless, but pain can occur
118
Nipple symptoms of breast ca?
shape in shape, bleeding, tethering, peau d'orange
119
Diagnosis of breast ca?
mammography and core biopsy
120
Who to refer for suspected ca referral (2ww) for breast ca?
- 30yrs+ with unexplained breast lump with or without pain - 50yrs+ and any of: discharge, retraction, changes of concern; in one nipple
121
Consider a suspected ca referral (2ww) for breast ca in who?
- skin changes that suggest breast ca - 30yrs+ with unexplained lump in axilla
122
Non-urgent referral for breast ca in who?
<30yrs with unexplained breast lump with or without pain
123
Symptoms suggestive of breast ca?
- axillary lump (unexplained) - breast lump (unexplained) - nipple changes - skin changes - DVT
124
Types of referrals for ca?
- immediate= acute admission or referral within few hrs - urgent= within 2w - very urgent= within 48hrs - non-urgent= general referral - suspected ca pathway= within national target for ca referral eg. 2ww
125
Most common type of breast ca?
invasive ductal carcinoma
126
Pathological assessment of breast ca involves what?
assessment of the tumour and lymph nodes- normally using sentinel lymph node biopsy (minimises morbidity of an axillary dissection)
127
Reconstruction for breast ca?
- option following any resectional procedure but type tailored to age and co-morbidities - common: latissimus dorsi myocutaneous flap and sub pectoral implants - want to avoid prosthesis= TRAM or DIEP flaps
128
Surgical options for breast ca: when is mastectomy indicated?
- multifocal tumour - central tumour - large lesion in small breast - DCIS >4cm - Pt choice
129
Surgical options for breast ca: when is wide local excision indicated?
- solitary lesion - peripheral tumour - small lesion in large breast - DCIS <4cm - pt choice
130
Large breast tumour that is unsutiable for breast conserving surgery?
mastectomy
131
How may central lesions in breast ca be managed?
breast conserving surgery where an acceptable cosmetic result may be obtained- rare in small breasts but more likely in large breast
132
Local recurrence rate of breast ca whatever surgery option was chosen?
5% or less at 5yrs
133
What index can be used to give indication of survival in breast ca?
Nottingham Prognostic Index
134
Calculation of Nottingham Prognostic Index?
Tumour Size x 0.2 + Lymph node score +Grade score
135
Nottingham Prognostic Index- lymph node and grade score score?
Score 1= 0 lymph nodes involved= Grade 1 Score 2= 1-3 lymph nodes= Grade 2 Score 3= >3= Grade 3
136
Prognosis from Nottingham Prognostic Index for breast ca?
score 2-2.4= 93% 5yr survival score 2.5-3.4= 85% 3.5-5.4= 70% >5.4= 50%
137
What does Nottingham Prognostic Index for breast ca not include that can affect survival?
vascular invasion and receptor status
138
Prior to surgery for breast ca, what determines Mx?
presence or absence of lymphadenopathy
139
Mx of breast ca: women with no palpable axillary lymphadenopathy at presentation should have what?
pre-op axillary USS before primary surgery if -ve then sentinel node biopsy to assess nodal burden
140
Mx of breast ca: women with palpable axillary lymphadenopathy at presentation should have what?
axillary node clearance at primary surgery
141
In the Mx of breast ca, what may happen if pt has axillary node clearance at primary surgery?
may lead to arm lymphedema and functional arm impairment
142
Mx of breast ca: when is whole breast radiotherapy recommended?
- all women after wide-local excision (can reduce recurrence by 2/3rds) - if had mastectomy and have T3-T4 tumours - if had mastectomy and have 4 or more +ve axillary nodes
143
When is adjuvant hormonal therapy offered for breast ca Mx?
if tumours are positive for hormone receptors
144
What receptors are tested for breast ca at time of initial histopathological diagnosis?
oestrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2)
145
Adjuvant hormonal therapy for breast ca after surgery if +ve for hormone receptors?
Tamoxifen= men and premenopausal women with ER +ve invasive breast ca Aromatase inhibitor eg. anastrozole= postmenopausal women with ER +ve
146
Biological therapy for breast ca?
Trastuzumab (Herceptin) for HER2 positive breast ca 3 w intervals for 1yr in combination to surgery, chemo, endocrine therapy and radiotherapy as appropriate
147
Chemotherapy for breast ca?
Regimen with a taxane and an anthracycline
148
Side effects of chemo for breast ca (regimen that contains a taxane and an anthracycline)?
neuropathy, neutropenia and hypersensitivity
149
When to give bisphosphonate therapy in the Mx of breast ca?
zoledronic acid as adjuvant therapy to post-menopausal women with node +ve invasive breast ca or node -ve but high risk recurrence
150
What to offer pts who are not receiving bisphosphonates who are starting aromatase inhibitors, treatment induced menopause or starting ovarian ablation/suprression therapy in Mx of breast ca?
DEXA scan
151
What radiotherapy is offered for pts with invasive breast ca having partial breast, whole breast or chest-wall radiotherapy without regional lymph node irradiation after breast conserving surgery or mastectomy?
external beam radiotherapy: 26Hy in 5 fractions over 1w
152
Chemo Mx for people with ER/PR/HER2 negative (triple negative) invasive breast ca?
neoadjuvant chemo regimen contains a platium and an anthracycline
153
Genetic testing for breast ca?
BRCA1 and BRCA2 mutations if under 50yrs with triple-negative breast ca and also those with no FHx of breast/ovarian ca
154
Mx for Paget's disease?
Offer breast-conserving surgery with removal of the nipple–areolar complex as an alternative to mastectomy for people with Paget's disease of the nipple that has been assessed as localised.
155
Breast reconstruction options for breast ca?
immediate reconstruction (during mastectomy surgery) or delayed in another operation
156
Cx of local treatment of breast ca?
- lymphoedema= arm, breast or chest wall - arm and shoulder mobility= so carry out upper limb exercises - menopausal symptoms
157
HRT and breast ca?
- stop HRT - don't offer HRT if Hx of breast ca - consider SSRI to relieve symptoms if not on tamoxifen
158
What can you consider for premenopausal women with ER +ve invasive breast ca?
ovarian function suppression to reduce risk of recurrence
159
How long to take tamoxifen or aromatase inhibitor for breast ca?
5yrs can continue taking to reduce recurrence
160
Can pt get pregnant on tamoxifen?
not while taking it or within 2m of stopping
161
Follow up imaging for pt who has been treated for breast ca?
annual mammography for 5yrs or longer until they enter screening programme
162
Summary of Mx of breast ca?
- Genetic testing= BRCA1 & BRCA2 - Hormone receptor testing= ER, PR, HER2 - Pre-op= USS axilla (if abnormal then USS guided needle sampling) - Surgery= mastectomy or breast conserving surgery. Also axillary lymph node clearance or SLNB (if no evidence of LN invol on USS) - Breast reconstruction= immediate or delayed - Endocrine therapy= tamoxifen (ER) or anastrasole (PR) (and maybe extended endocrine therapy- >5yrs) - Ovarian function supression - Adjuvant chemo - Radiotherapy= after breast conserving surgery or after mastectomy who are high risk of recurrence (eg. node +ve invasive breast ca) - Biological theraoy= transtuzumab (HER2) - Bisphosphonate?
163
Risk factors for breast ca?
- BRCA1, BRCA2 genes - 1st degree relative premenopausal relative with breast cancer (e.g. mother) - nulliparity, 1st pregnancy > 30 yrs (twice risk of women having 1st child < 25 yrs) - early menarche, late menopause - combined hormone replacement therapy, combined oral contraceptive use - past breast cancer - not breastfeeding - ionising radiation - p53 gene mutations - obesity - previous surgery for benign disease (?more follow-up, scar hides lump)
164
BRCA1 and BRCA2 gene increase risk of what?
40% lifetime risk of breast/ovarian ca
165
What is used for breast screening?
mammography radiography- detects small changes in breast before other S&S of breast ca develop
166
How often is the breast screening programme?
every 3yrs
167
When are women offered breast screening?
aged 50-70 should receive 1st invitation within 3yrs of 50th bday
168
Can women >70yrs get breast screening?
excluded from programme but can get screening by self-referral to local breast screening service
169
Who may be eligible for breast screening <50yrs?
if have increased risk eg. strong FHx
170
What info should women be given before participating in breast screening programme
- benefits and harms - organisation of screening - where it is done - preparing for mammogram - what to expect during appointment
171
Benefits of breast screening?
- early detection of breast ca - reduction in mortality
172
Harms of breast screening?
- over-diagnosis & unnecessary Tx - false positive mammograms - false reassurance so incorrect diagnosis - pain and discomfort - psychological distress, anxiety following a false positive
173
What people should be referred to breast clinic for screening from younger age?
- one first-degree female relative diagnosed with breast cancer at younger than age 40 years, or - one first-degree male relative diagnosed with breast cancer at any age, or - one first-degree relative with bilateral breast cancer where the first primary was diagnosed at younger than age 50 years, or - two first-degree relatives, or one first-degree and one second-degree relative, diagnosed with breast cancer at any age, or - one first-degree or second-degree relative diagnosed with breast cancer at any age and one first-degree or - second-degree relative diagnosed with ovarian cancer at any age (one of these should be a first-degree relative), or - three first-degree or second-degree relatives diagnosed with breast cancer at any age
174
What if mammogram comes back suspicious for breast ca?
1) mammogram 2) USS 3) if imaging concerning then biopsy: core needle biopsy 4) Pathology report= type of ca, hormone receptor status and grade 5) Staging= sentinel lymph node biopsy, CT
175
Types of breast cancer?
- invasive ductal carcinoma - invasive lobular carcinoma - ductal carcinoma-in situ (DCIS) - lobular carcinoma-in-situ (LCIS)
176
Most breast cancers arise from what?
Duct tissue (most) or lobular tissue (so ductal or lobular carcinoma) carcinoma-in-situ= local- hasn't spread invasive= spread
177
Invasive ductal carcinoma?
most common type breast ca (recently been named as No Special Type (NST); lobular and other rarer types classed as Special Type)
178
Rarer types of breast cancer?
- Medullary breast cancer - Mucinous (mucoid or colloid) breast cancer - Tubular breast cancer - Adenoid cystic carcinoma of the breast - Metaplastic breast cancer - Lymphoma of the breast - Basal type breast cancer - Phyllodes or cystosarcoma phyllodes - Papillary breast cancer
179
Other types of breast cancer that may be associated with underlying lesions (eg. other types of breast ca)?
- Paget's disease of the nipple - Inflammatory breast ca
180
Paget's disease of the nipple?
Eczematoid change of nipple associated with underlying breast ca 1-2% will have breast ca 1/2 have associated underlying mass lesion and 90% have invasive carcinoma Some without mass lesion will have underlying carcinoma and some will have carcinoma in situ
181
Inflammatory breast ca?
cancerous cells block lymph drainage resulting in inflamed appearance of breast rare
182
Most cases of cervical ca originate from where?
ecto- or endocervical mucosa in the cervical transformation zone
183
Cervical ca: what usually regressess?
low-grade dysplasia (cervical intraepithelial neoplasia 1- CIN1) but can progress to high grade dysplasia
184
When does cervical ca occur?
when high grade dysplastic lesions extend beyond the basement membrane of the cervical epithelium
185
2 most common types of cervical ca?
squamous cell carcinoma and adenocarcinoma
186
Main cause of cervical ca?
persistent infection- HPV (human papillomavirus)
187
How is HPV trsansmitted?
sexual intercourse
188
What subtype of HPV account for 2/3rds of cervical ca?
16 and 18; 33 HPV detected in 99% cervical ca
189
Only about 10% of all HPV infections become persistent, which puts women at risk of developing what?
precancerous cervical lesions
190
Time interval between HPV infection and development of precancerous lesions?
1-10yrs
191
RFs for development of cervical ca?
- increased exposure to HPV (eg. early age 1st intercourse) - impaired immune response to HPV infection eg. HIV or solid organ transplant - smoking - high parity - lower socioeconomic status - COCP
192
Peak incidence rate of cervical ca?
30-34yrs
193
Cx of cervical ca?
- psychosocial issues - sexual dysfunction - early menopause - loss of fertility - bladder & bowel dysfunction - pelvic or other pain - renal failure - haemeorrhage - fistuale - lymphoedema
194
CP of cervical ca?
- abnorm vaginal bleeding or discharge (not 2 to infection or other causes) - pelvic pain +/- dyspareunia - postmenopausal bleeding not due to HRT - abnorm cervix on exam= inflamed or friable, contact bleeding, visible ulcerating or necrotic lesion - symptoms of advanced disease (rare)
195
What to do if suspect cervical ca?
- urgent suspected ca referral (2ww) to colposcopy/gynaecology oncology - abdo, speculum and bimanual pelvic exam (may look normal) - assess for lymphadenopathy= inguinal and supraclavicular
196
Prevention of cervical ca?
- national cervical screening programme - national HPV vaccination programme - consistent use of condoms and practicing safe sex
197
Differential diagnosis for cervical ca?
- STI - Endometrial ca - endometriosis - ectropion or cervical polyp - hormonal contraception (in 1st 3m or 3-6m with coil or implant)
198
2 ww referral for cervical ca?
All women with unexplained postmenopausal bleeding should be referred to gynaecology for specialist assessment. Don't delay referral because a woman has had a previously normal cervical screening result Don't delay referral until after pregnancy if a woman is pregnant.
199
Cervical ca initial assessment after referral?
punch or excisional biopsy eg. electrosurgical excision and conization of suspicious lesions
200
What when cervical ca is confirmed after biopsy?
staging using FIGO system - MRI: tumour size and extent - CXR and assessment for hydronephrosis (renal USS, CT or MRI) for pre-Tx - sentinel node biopsy + PET/CT for lymph node invol. and mets
201
Common sites of mets from cervical ca?
lungs, liver, bone
202
Mx for cervical ca= Stage IA1 (microinvasive)
- loop electrosurgical excision and conisation: aim to acheive -ve margins to both ca and dysplasia - simple hysterectomy if don't want to preseve fertility
203
Mx for cervical ca: Stages IA2-IB2 (early stage disease)?
- radical hysterectomy and bilateral salpingectomy ( if fertility sparing appropriate in low risk) and/or bilateral oophorectomy with bilateral pelvic lymphadenectomy - radical trachelectomy (removal of cervix) and lymphadenoectomy can be considered instead for small tumours - may have adjuvant chemo or radio if intermediate/high risk recurrence
204
What factors may determine risk of recurrence in cervical ca?
tumour size, margin invl, lymph node invl
205
Mx for cervical ca: Stage IB3-IVA (locally advanced)?
- external beam radio, intracavity brachytherapy (radiation source placed in uterus & vagina) and chemo 1st line - surgery not recommended as unlikely to be curative
206
Mx of cervical ca: Stage IVB (spread to distant organs)?
systemic chemo 1st line
207
Mx options for recurrent or metastatic cervical ca?
- salvage surgery= pelvic exenteration (removal of female reproductive organs, lower urinary tract, portion of rectosigmoid bowel) if chemo failed and confined to central pelvis - chemo and/or radiotherapy if surgery not controlled disease
208
What is a radical hysterectomy?
resection of cervix, uterus, parametria and cuff of upper vagina
209
Most common type of cervical ca?
squamous cell cancer
210
Mechanism of HPV causing cervical ca?
HPV 16 & 18 produce the oncogenes E6 and E7 retrospectively E6 inhibits p53 tumour supressor gene E7 inhibits RB supressor gene
211
What is an oncogene?
mutated gene that has potential to cause cancer
212
What. HPV subtypes are non-carcinogenic and associated with genital warts?
6 & 11
213
Infected endocervical cells (infected with HPV) may undergo changes resulting in the development of what?
Koilocytes
214
Characteristics of koilocytes?
- enlarged nucleous - irregular nuclear membrane contour - nucleus stains darker than normal (hyperchromasia) - perinuclear halo
215
What is the Mx of cervical ca determined by?
FIGO staging and wishes of pt to maintain fertility
216
Stages of the FIGO staging for cervical ca?
IA IB II III IV
217
FIGO staging for cervical ca: stage IA?
Confined to cervix, only visible by microscopy and less than 7 mm wide: A1 = < 3 mm deep A2 = 3-5 mm deep
218
FIGI staging for cervical ca: stage IB?
Confined to cervix, clinically visible or larger than 7 mm wide: B1 = < 4 cm diameter B2 = > 4 cm diameter
219
FIGO staging for cervical ca: stage II?
Extension of tumour beyond cervix but not to the pelvic wall A = upper two thirds of vagina B = parametrial involvement
220
FIGO staging for cervical ca: stage III?
Extension of tumour beyond the cervix and to the pelvic wall A = lower third of vagina B = pelvic side wall NB: Any tumour causing hydronephrosis or a non-functioning kidney is considered stage III
221
FIGO staging for cervical ca: stage IV?
Extension of tumour beyond the pelvis or involvement of bladder or rectum A = involvement of bladder or rectum B = involvement of distant sites outside the pelvis
222
What is hydronephrosis?
urine builds up in kidneys due to blockage in ureters so they swell eg. can be a Cx of advanced cervical ca
223
Prognosis of cervical ca?
FIGO stage I= 99% 1yr survival; 96% 5yr II= 85%; 54% III= 74%; 38% IV= 35%; 5%
224
Cx of cone biopsy or radical trachelectomy eg. in cervical ca?
preterm birth in future pregnancies
225
Cx of radical hysterectomy?
ureteral fistula
226
Short term Cx of radiotherapy for cervical ca?
diarrhoea, vaginal bleeding, radiation burns, pain on micturition, tiredness/weakness
227
Long term Cx of radiotherapy for cervical ca?
ovarian failure, fibrosis of bowel/skin/bladder/vagina, lymphoedema
228
Cervical ca screening for women aged?
25-64yrs (first invitation issued at 24.5yrs so ensure screening can be done by 25th bday)
229
Recall intervals for cervical ca screening?
25-49yrs= recall every 3yrs (invitations issued 34.5m after previous test) 50-64yrs= every 5yrs (58.5m after previous)
230
Can people 65yrs and older get cervical screening?
invited if recent cervical cytology abnormal or if not had screening since 50yrs and request one
231
What does NHSCSP (cervical screening) involve?
- HPV screening= identify people with high-risk HPV (hrHPV) - Liquid based cytology (if hrHPV found)= detect early abnormalities of cervix, if untreated can lead to ca - Colposcopy= diagnose cervical intraepithelial neoplasia (CIN) and to differentiate high-grade lesions from low-grade abnormalities in people with abnormal cytology
232
Cervical ca screening, what if hrHPV detected?
cytology if this is abnormal then colposcopy
233
Cervical ca screening= hrHPV +ve and negative cytology?
repeat HPV test at 12m - if -ve then return to normal recall - if +ve then repeat HPV in 12m again - if -ve at 24m then return normal recall - if +ve at 24m then refer to colposcopy
234
Cervical ca screening= hrHPV +ve with cytology abnormal at 12 or 24m?
refer to colposcopy
235
Cervical ca screening= hrHPV test unavailable or cytology inadequate?
repeat sample in <3m - if inadequate at 24m repeat text, these are exception and refer to colposcopy - 2 consecutive inadequate or unavailable tests then refer to colposcopy
236
Cervical ca screening= colposcopy normal and adequate?
follow up at 12m screening, if then HPV -ve then return to normal recall
237
Cervical ca screening= colposcopy inadequate?
repeat screening and colposcopy in 12m; if normal and HPV -ve then return to routine recall
238
Cervical ca screening: cytology negative means what?
no abnormality detected
239
Cervical ca screening: if cytology is abnormal, the cervical samples may show what? (6)
- borderline changes in squamous or endocervical cells - low grade dyskaryosis - high-grade dyskaryosis (moderate) - high-grade dyskaryosis (severe) - invasive squamous cell carcinoma - glandular neoplasia
240
Cervical ca screening: if cytology is inadequate, this may be because the cervical sample was...? (5)
- taken but the cervix was not fully visualised - taken in inappropriate manner eg. using not approved sampling device - contains insufficient cells - contains obscuring element eg. lubricant, blood, inflamm - incorrectly labelled
241
What does colposcopy look at in cervical ca screening?
any abnormal changes in cervix which may indicate pre-cancerous changes (cervical intraepithelial neoplasia [CIN]) or the presence of cancer
242
What chemicals are usually applied to cervix during colposcopy in cervical ca screening?
acetic acid = abnormal areas (such as CIN) tend to turn white (sometimes referred to as acetowhite). If iodine solution= normal tissue (on the outside of the cervix) stains dark brown. Pre-cancerous abnormalities may not stain with iodine. The cells on the inner part of the cervix do not stain brown.
243
What may be done on colposcopy to confirm diagnosis of cervical ca?
biopsy
244
Can pregnant women be offered cervical screening?
- if called while pregnant, defer until 3m post-partum + - if previous test was abnormal, do not delay colposcopy (can do in late 1st or early 2nd tri; if low grade changes can delay until after delivery; if seen in early preg may need another assessment in late 2nd tri)
245
If pt has been treated for CIN, when should they be followed up for repeat cervical sample?
6m after Tx to test for cure
246
What is cervical intraepithelial neoplasia (CIN)?
abnormal changes in the transformation zone of cervix
247
Cervical dysplasia may indicate what?
HIV
248
Cervical intraepithelial neoplasia (CIN) grade 1 (CIN1)?
sometimes referred to as low-grade squamous intraepithelial lesions) — one-third of the thickness of the surface layer of the cervix is affected.
249
Cervical intraepithelial neoplasia (CIN) grade 2 (CIN2)?
two-thirds of the thickness of the surface layer of the cervix is affected.
250
Cervical intraepithelial neoplasia (CIN) grade 3 (CIN3)?
(sometimes called high-grade or severe dysplasia or stage 0 cervical carcinoma in situ) — the full thickness of the surface layer is affected.
251
CIN may exist at any one of the three stages, eg?
CIN1 lesions are morphological correlates of HPV infections. CIN2/3 lesions (collectively referred to as CIN2+) are correlates of cervical pre-cancers that, if left untreated, may progress to cervical cancer.
252
How often should pt have cervical ca screening if have HIV?
annually and colposcopy at diagnosis
253
What does dyskaryosis in cervical ca mean?
percancerous changes in cervical cells: can be early indication of cervical ca or HPV infection
254
Cervical ca: mild dyskaryosis?
Indicates low-grade abnormalities in the cervical cells. Often corresponds to CIN1, which is a mild change in the cells and typically linked to an HPV infection. In many cases, mild dyskaryosis can resolve on its own without treatment, especially if caused by transient HPV infections.
255
Cervical ca: moderate dyskaryosis?
Indicates more significant abnormality. Typically corresponds to CIN2 , which is a higher risk of progression to cervical cancer than CIN1. Treatment may be needed to prevent further progression.
256
Cervical ca: severe dyskaryosis?
Indicates severely abnormal cells. Usually corresponds to CIN3, a precancerous stage with a significant risk of progression to cervical cancer if untreated. Requires further diagnostic testing and often surgical treatment to remove the abnormal tissue.
257
What if dyskaryosis is detected on cervical smear?
colposcopy +/- biopsy
258
Presenting features of colorectal ca may include what?
- change in bowel habits: C, D or alternating; increase frequency - rectal bleeding: bright red or melena - abdo pain/discomfort - unexplained weight loss: advanced -anaemia: fatigue, weakness, SOB - bowel obstruction: advanced- severe abdo pain, N&V
259
Why may pt get abdo pain/discomfort/cramping with colorectal ca?
may be due to tumour obstructing bowel or causing inflam
260
Why may pt with colorectal ca have anaemia?
chronic bleeding from the tumour
261
Locations of ca in colorectal cancer?
rectal (40%) sigmoid (30%) descending colon (5%) transverse colon (10%) ascending colon and caecum (15%)
262
Types of colorectal (colon) ca?
1) sporadic (95%) 2) hereditary non-polyposis colorectal carcinoma (HNPCC, 5%) 3) familial adenomatous polyposis (FAP, <1%)
263
What may sporadic colon ca be due to?
genetic mutations
264
Examples of genetic mutations that may cause colon (colorectal ca)?
- allelic loss of APC gene - activation of K-ras oncogene - deletion of p53 and DCC tumour suppressor genes
265
What is HNPCC (Lynch syndrome)?
autosomal dominant condition, most common form of inherited colon ca 90% pts develop ca, often proximal colon, poorly differentiated and highly aggressive
266
What mutation and genes are involved in HNPCC (Lynch syndrome)?
7 mutations, which affect genes invl in DNA mismatch repair leading to microsatelilite instability. Genes: - MSH2 (60%) - MLH1
267
Pts with HNPCC are also at higher risk of what?
other ca eg. endometrial ca
268
What is sometimes used to aid diagnosis of HNPCC?
Amsterdam criteria: - at least 3 family members with colon ca - the cases span at least 2 generations - at least one case diagnosed before age of 50yrs
269
What is FAP?
rare autosomal dominant condition which leads to formation of hundreds of polyps by age 30-40yrs pts inevitably develop carcinoma (lifetime risk near 100%)
270
What is FAP due to?
mutation in tumour supressor gene called adenomatous polyposis coli gene (APC) located on chromosome 5
271
Ix and Mx for FAP?
Ix= genetic testing- analyse DNA from pts WBC Mx= total proctocolectomy with ileal pouch anal anastomosis (IPAA) formation in their 20s
272
Pts with FAP are also at risk from what?
duodenal tumours
273
Variant of FAP?
Gardner's syndrome- also feature osteomas of skull & mandible, retinal pigmentation, thyroid carcinoma and opidermoid cysts on the skin
274
What does FAP stand for?
Familial Adenomatous Polyposis
275
How to stage colorectal ca?
- carcinoembryonic antigen (CEA) - CT chest, abdo, pelvis - entire colon evaluated with colonoscopy or CT colonography - if tumour lies below peritoneal reflection then also need mesorectum evaulated with MRI
276
Staging system for colorectal ca?
TNM once staging complete then MDT meeting to formulate Mx plan
277
Treatment options for colorectal ca?
- surgery - chemo - radio - targeted therapies
278
Ca of colon is nearly always treated with what?
surgery
279
Only option for cure in pts with colon ca?
resectional surgery
280
Confounding factors that will goven choice of procedure for surgery for colon ca?
eg. tumour pt from HNPCC family may be better served with panproctocolectomy rather than segmental resection
281
Treatment for colon ca: surgery- what is needed for anastomosis to heal?
following resection, need decision regarding restoration of continuity for anastomosis to heal= adequate blood supply, mucosal apposition and no tissue tension
282
What is an anastomosis?
surgical or natural connection between 2 structures eg. blood vessels, intestine, tubes critical in many surgeries to ensure that normal flow and function are maintained after structural changes
283
Surgical options when colon ca presents with an obstructing lesion?
stent it or resect unusual now to defunction a colonic tumour with proximal loop stoma (this differs from situation in rectum)
284
The operations for colon ca are segmental resections based on what?
blood supply and lymphatic drainage
285
Type of resection and anastomosis for cancer of the caecal, ascending or proximal transverse colon?
Type of resection= right hemicolectomy Anastomosis= ileo-colic
286
Type of resection and anastomosis for cancer of the distal transverse, descending colon?
Type of resection= left hemicolectomy Anastomosis= colo-colon
287
Type of resection and anastomosis for cancer of the sigmoid colon?
Type of resection= high anterior resection Anastomosis= colo-rectal
288
Type of resection and anastomosis for cancer of the upper rectum?
Type of resection= anterior resection (TME) Anastomosis= colo-rectal
289
Type of resection and anastomosis for cancer of the low rectum?
Type of resection= anterior resection (low TME) Anastomosis= colo-rectal (+/- defunctioning stoma)
290
Type of resection and anastomosis for cancer of the anal verge?
Type of resection= abdomino-perineal excision of rectum Anastomosis= none
291
Types of stoma?
Colostomy: Bypass the colon, output is usually solid. Ileostomy: Bypass the small intestine, output is usually liquid. Urostomy: Bypass the bladder, output is urine. Jejunostomy and Gastrostomy: Used for feeding rather than waste diversion. (opening in jejunum or in stomach respectively)
292
Temporary vs permanent stomas?
Temporary Stomas: Created when the bowel or bladder needs time to heal (e.g., after an injury or surgery). They are later reversed when healing is complete. Permanent Stomas: Created when the underlying condition (e.g., cancer, severe Crohn’s disease) requires permanent removal or bypass of part of the digestive or urinary tract.
293
When is chemotherapy used in colorectal ca?
in neoadjuvant setting (particularly for rectal ca), adjuvant setting and for metastatic disease
294
Common chemo regimens for colorectal ca?
FOLFOX and FOLFIRI
295
When is radiation therapy used for colorectal ca?
predominantly for rectal ca in the neoadjuvant or adjuvant setting
296
Targeted therapies for colorectal ca?
Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), particularly for metastatic disease
297
Emergency surgery in colorectal ca in a setting where the bowel has perforated so the risk of an anastomosis is much greater? (particulary when the anastomosis needed is colon-colon)
end colostomy is safer and can be reversed - resection of sigmoid colon and end colostomy is fashioned in operation= Hartmann's procedure - left sided resections more risky, ileo-colic anastomoses are relatively safe even in emergencies and don't need to be defunctioned
298
What is used to guide referral in suspected colorectal ca?
Faecal Immunochemical Test (FIT) instead of doing colonoscopy 1st line
299
What scenarios should pt get FIT test before colorectal ca referral?
- abdo mass - change in bowel habit - iron def anaemia - 40yrs+ with unexplained weight loss & abdo pain - <50yrs with rectal bleeding + abdo pain or weight loss - 50yrs+ with rectal bleeding, weight loss or abdo pain - 60yrs+ with anaemia even in absence of iron def
300
What if pt needs FIT test but already had a negative result through the NHS screening programme?
still need another one
301
What if pt with rectal mass, unexplained anal mass or unexplained anal ulceration?
do not need FIT test, just consider referral for ?colorectal ca
302
What if FIT test comes back +ve?
refer on suspected ca pathway
303
What if FIT test negative?
- safety net - refer on suspected ca pathway if ongoing signif concern (abdo mass) - still Ix for underlying diagnosis
304
NHS screening programme for bowel ca offered to who?
every 2yrs to people 50-74yrs (England & Scotland) Wales: 51-74 NIreland: 60-74hrs
305
How is FIT testing done in NHS screening programme for bowel ca?
Invitation letter followed by test kit: end of test tick dipped into single bowel motion, placed back in tube and returned in envelope
306
How do pt get results from FIT test from the screening programme?
letter sent to pts home within 2 weeks of receiving the kit and GP informed electronically
307
Abnormal FIT test on NHS screening programme?
offered colonoscopy
308
Colonoscopy results if indicated after FIT test (following screening programme)?
No abnormal or low-risk adenoma= return to routine recall Intermediate or high risk adenoma= invited for colonoscopic surveillance/review Cancer= refer for Tx Other pathology eg. IBD or diverticulosis= referred for Tx
309
Possible harms of bowel screening?
anxiety; Cx of colonoscopy (bleeding, bowel perforation); inappropriate reassurance from -ve screening result
310
How can primary care support the bowel ca screening programme?
- promoting uptake - ensure that pts are aware that not all ca will be detected by screening - -ve results should not be used to guide Ix of pt presenting with symptoms of bowel ca
311
What is a FIT test?
type of faecal occult blood (FOB) test which uses antibodies that specifically recognise human Hb used to detect and quantify amount of human blood in single stool sample abnormal result offered colonoscopy
312
Most colorectal ca develop from what?
adenomatous polyps
313
If pt gets colonoscopy following FIT test, how many will be found to have ca?
1/10 5/10 normal 4/10 polpys which may be removed (premalignant potential)
314
Where is endometrial ca classically seen?
post-menopausal women 25% do occur before menopause
315
Prognosis of endometrial ca?
good due to early detection
316
RFs for endometrial ca?
XS oestrogen: - nulliparity - early menarche - late menopause - unopposed oestrogen metabolic syndrome: - obesity - DM - PCOS tamoxifen hereditary non-polyposis colorectal carinoma (HNPCC)
317
Protective factors for endometrial ca?
- multiparity - COCP - smoking
318
Does HRT and the COCP increase or decrease the risk of endometrial ca?
Reduces the risk addition of progestogen to oestrogen reduces the risk as oestrogen is no longer unopposed
319
Postmenopausal bleeding classic symptom of what?
endometrial ca
320
Features of endometrial ca?
- postmenopausal bleeding, usually slight and intermittent initially before becoming heavier - premenopausal= menorrhagia or intermenstrual bleeding - pain not common, signifies extensive disease - vaginal discharge unusual
321
Who should be referred using suspected ca pathway for endometrial ca?
all women >=55yrs who present with postmenopausal bleeding consider if <55
322
1st line Ix for endometrial ca once referred?
trans-vaginal USS: normal endometrial thickness (<4mm) has a high negative predictive value hysteroscopy with endometrial biopsy
323
Mx for endometrial ca?
surgery - localised disease= total abdo hysterectomy with bilateral salpingo-oophorectomy high-risk disease= postop radiotherapy
324
Frail elderly women with endometrial ca not suitable for surgery?
progestogen therapy
325
How is post-menopausal bleeding defined?
unexplained vaginal bleeding more than 12m after menstruation has stopped because of the menopause
326
Consider a direct access USS to assess for endometrial ca in women aged 55yrs and over with what?
Unexplained symptoms of vaginal discharge who: - Are presenting with these symptoms for the first time, or - Have thrombocytosis, or - Report haematuria, or Visible haematuria, and: - Low haemoglobin levels, or - Thrombocytosis, or - High blood glucose levels.
327
Who is typically affected by gastric ca?
older people (1/2 are >75yrs) and male
328
Most common type of gastric ca?
gastric adenocarcinoma
329
Where does gastric adenocarcinoma arise from?
glandular epithelium of the stomach lining
330
RFs for gastric ca?
- Helicobacer pylori - pernicious anaemic, atrophic gastritis - diet - ethnicity: Japan, China - smoking - blood group A
331
Why is H.pylori a RF for gastric ca?
triggers inflam of the mucosa -> atrophy and intestinal metaplasia -> dysplasia
332
What type of diet increases risk of gastric ca?
salt and salt-preserved foods nitrates
333
Features of gastric ca?
abdo pain= vague, epigastric, dyspepsia weight loss & anorexia N&V dysphagia: esp if ca arises in proximal stomach overt upper GI bleeding in minority Virchow's node & Sister Mary Joseph's node
334
What lymph nodes may be palpated if there is lymphatic spread in gastric ca?
left supraclavicular lymph node (Virchow's node) periumbilical nodule (Sister Mary Joseph's node)
335
Ix and diagnosis for oesophago-gastric ca?
oesophago-gastro-duodenoscopy with biopsy
336
Signet ring cells?
may be seen in gastric ca on biopsy contain large vacuole of mucin which displaces the nucleus to one side high no. of signet ring cells= worse prognosis
337
How to stage gastric ca?
- CT chest, abdo and pelvis= ?mets - endoscopic USS: if will guide Mx - F18 FDG-PET scan: if ? metastatic disease -pre-op staging laparoscopy: if potentially curable gastric
338
Mx of gastric ca?
surgical options depend on extent and site, include: - endoscopic mucosal resection - partial gastrectomy - total gastrectomy - chemotherapy
339
Mx of T1N0 oesophageal ca?
endoscopic mucosal resection for staging
340
Mx for T1bN0 SCC of the oeophagus?
- definitive chemo or - surgical resection pt choice
341
Surgical Tx of oesophageal ca?
open or minimally invasive oesophagectomy
342
Lymph node dissection in oesophageal and gastric ca?
When performing curative gastrectomy for gastric ca= consider D2 lymph node dissection Curative oesophectomy= consider two-field lymph node dissection
343
Mx for localised oesophageal and oesophago-gastric junctional adenocarcinoma (excluding T1N0) who will have surgical rection, offer choice of what?
- chemo before or before & after surgery - chemoradiotherapy before surgery
344
What to offer pt who is having radical surgical resection for gastric ca?
chemo before and after surgery or chemo/chemoradiotherapy after surgery for those with curative intent and didn't have chemo before
345
Mx for SCC of oesophagus (resectable and non-metastatic)?
- radical chemoradio or - chemoradio before surgical resection
346
Mx for non-metastaic oesophageal ca that is not suitable for surgery?
palliative Mx: - chemoradio for non-metastatic that can be encompassed within a radiotherapy field if can't be encompassed, consider 1 or more: - chemo - local tumour Tx (stenting or palliative radio) - best supportive care after Tx reassess response and reconsider if surgery is an option
347
1st line palliative chemo for people with HER2-positive metastatic adenocarcinoma of stomach or oesophago-gastric junction?
trastubzumab (in combination with cisplatin and capecitabine)
348
1st line palliative combination chemo to pt with advanced oesophago-gastric ca who have performance status 0 to 2 and no signif comorbidities?
double Tx= 5-fluorouracil or capecitabine in combination with cisplatin or oxaliplatin triple Tx= 5-fluorouracil or capecitabine in combination with cisplatin or oxaliplatin plus epirubicin.
349
What can you offer pts with luminal obstruction in oesophageal and oesophageal-gastric junctional ca?
self-expanding stents or radiotherapy
350
What can you offer pt with outflow obstruction in gastric ca?
uncovered self-expanding metal stents or palliative surgery
351
What to offer pt immediately after having radical surgery for oesophageal and oesophago-gastric junctional ca?
enteral or parenteral nutrition
352
Most common malignancy affecting children?
ALL
353
What does ALL stand for?
Acute lymphoblastic leukaemia
354
Peak incidence of ALL?
2-5yrs boys slightly more common
355
Features of ALL may be divided into what?
those predictable by bone marrow failure eg. anaemia, neutropaenia, thrombocytopenia
356
Features of ALL?
- anaemia= lethargy and pallor - neutropenia= frequent or severe infection - thrombocytopenia= easily bruising, petechiae - bone pain - splenomegaly - hepatomegaly - fever in up to 50% - testicular swelling
357
Why may child get bone pain with ALL?
secondary to bone marrow infiltration
358
Types of ALL?
- common ALL (75%), CD10 present, pre-B phenotype - T-cell ALL (20%) - B-cell ALL (5%)
359
ALL poor prognostic factors?
- age <2yrs or >10yrs - WBC >20*10^9/l at diagnosis - T or B cell surface markers - non-Caucasian - male
360
More common form of acute leukaemia in adults?
acute myeloid leukaemia
361
AML may occur as what?
primary disease or following a secondary transformation of a myeloproliferative disorder
362
What does AML stand for?
acute myeloid leukaemia
363
Features of AML?
related to bone marrow failure - anaemia= pallor, lethargy, weakness - neurtopenia= WBC count may be v high, functioning neutrophil levels may be low leading to frequent infections - thrombocytopenia= bleeding - splenomegaly - bone pain
364
Poor prognostic factors of AML?
>60yrs >20% blasts after first course of chemo cytogenetics= deletions of chromosome 5 or 7
365
Classification of AML?
French-American-British (FAB) MO - undifferentiated M1 - without maturation M2 - with granulocytic maturation M3 - acute promyelocytic M4 - granulocytic and monocytic maturation M5 - monocytic M6 - erythroleukaemia M7 - megakaryoblastic
366
Acute promyelocytic leukaemia M3 (APML, the M3 subtype of AML)?
associated with t(15;17) fusion of PML and RAR-alpha genes presents younger than other types of AML (average = 25 years old) Auer rods (seen with myeloperoxidase stain) DIC or thrombocytopenia often at presentation good prognosis
367
Don't need to know substypes of AML except what?
Acute promyelocytic leukaemia (APML, the M3 subtype of AML)
368
What is APML associated with?
the t(15;17) translocation which causes fusion of the PML and RAR-alpha genes
369
Features of APML?
- presents younger than other types of AML (average=25yrs) - DIC or thrombocytopenia often - good prognosis
370
Mx of APML?
all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemo
371
What type of leukaemia is treated with all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemo?
APML (subtype of AML)
372
Cx of CLL?
- anaemia - hypogammaglobulinaemia= recurrent infections - warm autoimmune haemolytic anaemia (in 10-15%) - transformation to high-grade lymphoma (Richter's transformation)
373
What is Ritchter's transformation?
occurs when leukaemia cells enter lymph node and change into high-grade, fast-growing non-Hodgkin's lymphoma pts become unwell very suddenly
374
Ritcher's transformation is indicated by one the following symptoms....
lymph node swelling fever without infection weight loss night sweats nausea abdominal pain
375
Pt with CLL suddenly becomes very unwell?
Ritcher's transformation
376
What does CLL stand for?
chronic lymphocytic leukaemia
377
What causes CLL?
monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
378
Most common form of leukaemia seen in adults?
CLL
379
Features of CLL?
- often asymptomatic= picked up incidental finding of lymphocytosis - constitutional: anorexia, weight loss - bleeding, infections - lymphadenopathy more marked than CML
380
Ix for CLL?
- Immunophenotyping KEY - FBC - Blood film= smudge cells (smear cells)
381
Immunophenotyping for CLL?
most cases can be identified using panel of antibodies specific for CD5, CD19, CD20, CD23
382
What would FBC for CLL show?
anaemia (due to bone marrow replacement or autoimmune haemolyic anaemia) and thrombocytopenia (due to bone marrow replacement or immune thrombocytopenia- ITP)
383
Smudge cells (smear cells on blood film)?
CLL
384
Auer rods on myeloperoxidase stain?
AML (APML)
385
Philadelphia chromosome is present in more than 95% of pts with what?
CML
386
What is the philadelphia chromosome in CML due to?
translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.
387
Presentation of CML?
60-70yrs - weight loss and sweating COMMON - marked splenomegaly= abdo discomfort - increase in granulocytes at different stages of maturation +/- thrombocytosis - decrease leukocyte alkaline phosphatase - may undergo blast transformation (AML in 80%, ALL in 20%)
388
Mx of CML?
Imatinib 1st line - hydroxyurea - interferon-alpha - allogenic bone marrow transplant
389
What is imatinib used for 1st line Mx of CML?
inhibitor of the tyrosine kinase associated with the BCR-ABL defect very high response rate in chronic phase CML
390
What does CML stand for?
Chronic myeloid leukaemia
391
Consider very urgent FBC (within 48hrs) to assess for leukaemia in adults with any of the following?
pallor persistent fatigue unexplained fever Unexplained persistent or recurrent infection. Generalized lymphadenopathy. Unexplained bruising. Unexplained bleeding. Unexplained petechiae. Hepatosplenomegaly.
392
When to refer children and young people for immediate specialist assessment for leukaemia if they have what?
unexplained petechiae or hepatosplenomegaly
393
When to do a very urgent FBC (within 48hrs) to assess for leukaemia in children and young people?
Pallor. Persistent fatigue. Unexplained fever. Unexplained persistent infection. Generalized lymphadenopathy. Persistent or unexplained bone pain. Unexplained bruising. Unexplained bleeding.
394
Way to remember leukaemia ages?
ALL= <5 & >45 CeLLmates= >55, smudge cells have CoMmon= >65, philadelphia chromosome AMbitions= >75, aurer rods
395
Way to remember some key info about leukaemia types?
ALL= ALL children have headaches because they were doing meth (methotrexate used to Tx ALL) AML= enAML (dental problems) and when you open your mouth you go ahhhh (aurer rods) CLL= geting smudged (smudge cells) in club rituximab (used to Tx) CML= CML and gout (Cx) got married in Philidelphia (chromosome)
396
Refer people using suspected ca referral for lung ca if they...?
- have CXR that suggests lung ca or - 40yrs+ with unexplained haemoptysis
397
Offer urgent CXR (within 2w) to assess for lung ca in people aged 40yrs+ if they have 2 or more of what symptoms, or if they have ever smoked and had one or more of the following unexplained symptoms?
- cough - fatigue - SOB - chest pain - weight loss - appetite loss
398
Consider CXR (within 2w) to assess for lung ca in people aged 40yrs+ and with any of the following...
- persistent or recurrent chest infection - clubbing - supraclavicular lymphadenopaty or persistent cervical lymphadenopathy - chest signs consistent of lung ca - thrombocytosis
399
Most mesotheliomas are what?
pleural peritoneal can occur
400
Features of lung ca?
persistent cough haemoptysis dyspnoea chest pain weight loss and anorexia hoarseness laryngeal nerve superior vena cava syndrome
401
When is hoarseness seen in lung ca?
with Pancoast tumours pressing on the recurrent laryngeal nerve
402
Examination findings of lung ca?
- fixed monophonic wheeze - clubbing - supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
403
What is paraneoplastic syndrome?
rare disorders that occur when immune system has a reaction to ca
404
Paraneoplastic features in small cell lung ca?
- ADH - ACTH (not typical)- HTN, hyperglucaemia, hypokalaemia, alkalosis and muscle weakness are more common than buffalo hump ect - Lamber-Eaton syndrome
405
Paraneoplastic features of squamous cell lung ca?
- parathyroid hormone-related protein (PTH-rp) secretion causing hypercalcaemia - clubbing - hypertrophic pulmonary osteoarthropathy (HPOA) - hyperthyroidism due to ectopic TSH
406
Paraneoplastic features of adenocarcinoma lung ca?
- gynaecomastia - HPOA
407
Cx of lung ca?
hoarseness stridor
408
What may be noted on bloods for pt with lung ca?
raised platelets (thrombocytosis)
409
1st line Ix for lung ca?
CXR (10% sometimes CXR normal)
410
Ix for lung ca?
1st line= CXR Gold= CT - Bronchoscopy with biopsy using endobrachial USS - PET scan= non-small lung ca to establish eligability for cure; 18-fluorodeoxygenase if preferentially taken up by neoplastic tissue - bloods= raised platelets
411
3 subtypes of non-small cell lung ca?
- Squamous cell carcinoma - Adenocarcinoma - Large cell lung carcinoma
412
Lung ca: squamous cell cancer?
typically central cavitating lesions are more common than other types HPOA
413
What is squamous cell lung ca associated with?
Finger clubbing and PTHrP secretion -> hypercalcaemia
414
Most common type of lung ca in non-smokers?
adenocarcinoma
415
Lung ca: adenocarcinoma?
- typically peripheral - most common in lung ca in non-smokers, but majority are still smokers
416
Lung ca: large cell lung carcinoma?
- typically peripheral - anaplastic, poorly differentiated tumours with poor prognosis - may secrete B-HCG
417
Anaplastic?
term used to describe ca cells that divide rapidly and have little to no resemblance to normal cells
418
Mx for non-small cell lung ca?
- only 20% suitable for surgery - curative or palliative radiotherapy - poor response to chemo
419
What is performed prior to surgery in non-small cell lung ca if suitable for surgery?
mediastinoscopy as CT doesn't always show mediastinal lymph node invl.
420
Non-small cell lung ma Mx: contraindications to surgery?
assess general health stage IIIb or IV (i.e. metastases present) FEV1 < 1.5 litres is considered a general cut-off point (for lobectomy or <2 for pneumonectomy; sometimes need further lung function tests as operations may still go ahead based on results) malignant pleural effusion tumour near hilum vocal cord paralysis SVC obstruction
421
Features of small cell lung ca?
- usually central - arise from APUD* cells - associated with ectopic ADH, ACTH secretion - ADH → hyponatraemia - ACTH → Cushing's syndrome - ACTH secretion can cause bilateral adrenal hyperplasia, the high levels of cortisol can lead to hypokalaemic alkalosis Lambert-Eaton syndrome
422
Lambert-Eaton syndrome in small cell lung ca?
antibodies to voltage gated calcium channels causing myasthenic like syndrome
423
Small cell lung ca is usually what by the time of diagnosis?
metastatic disease
424
Mx for small cell lung ca?
pts with very early stage disease (T1-2a, N0, M0) are considered for surgery. however, most pts with limited disease receive a combination of chemotherapy and radiotherapy pts with more extensive disease are offered palliative chemotherapy
425
What do small cell lung ca arise from?
APUD cells: Amine - high amine content Precursor Uptake - high uptake of amine precursors Decarboxylase - high content of the enzyme decarboxylase
426
Types of lung ca?
Small cell lung ca Non-small cell lung ca: - adenocarcinoma - squamous - large cell - alveolar cell carcinoma - bronchial adenoma
427
How is lung ca classified?
histologically as SCLC or NSCLC due to different features, Mx and prognosis
428
What type of lung ca has worse prognosis?
small cell (15%)
429
Most common type of lung ca?
adenocarcinoma (NSCLC) often seen in non-smokers high no of cases due to increased use of low-tar cigarettes
430
What type of lung ca most commonly has cavitating lesions?
Squamous (NSCLC)
431
NSCLC: alveolar cell carcinoma?
not related to smoking ++ sputum
432
What type of lung ca is mostly carcinoid?
bronchial adenoma (NSCLC)
433
SCLC vs NSCLC?
SCLC - 10-15% - fast growing, aggressive - often widespread at diagnosis - only one major type (small cell carcinoma) - strong association with smoking - limited stage and extensive stage - more likely to present with paraneoplastic symptoms eg. SIADH, Cushings - Tx: chemo and radio; surgery rare due to early mets - poor prognosis (12-18m limited stage; 6-12m extensive) - fewer mutations, TP53, RB1 - less responsive to immunotherapy NSCLC - 85-90% - slower growing - may be localised at diagnosis - Types: adenocarcinoma, SCC, large cell carcinoma - associated with smoking and genetic mutations - Staged I to IV - CP: cough, chest pain, weight loss like SCLC but less likely to have paraneoplastic symtpoms - surgery option in early stages; chemo, radiation and immunotherapy in advanced - better prognosis - Mutations: EGFR, ALK, ROS1 and KRAS, more common in adenocarcinoma - more responsive to immunotherapy
434
Burkitt's lymphoma?
high-grade B-cell neoplasm
435
2 major forms of Birkitt's lymphoma?
- Endemic (African) form - Sporadic form
436
Burkitt's lymphoma: endemic (African) form?
typically invl. maxilla or mandible
437
Burkitt's lymphoma: sporadic form?
abdominal eg ileo-caecal tumours are the most common form; more common in pts with HIV
438
What is Burkitt's lymphoma associated with? (gene)
c-myc gene translocation, usually t(8:14)
439
What virus is implicated in the development in the development of the African form of Burkitt's lymphoma and to lesser extent the sporadic form?
EBV
440
Microscopy findings in Burkitt's lymphoma?
'starry sky' appearance= lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
441
Mx for Burkitt's lymphoma?
Rasburicase often given before then chemotherapy
442
What does chemotherapy used for Burkitt's lymphoma tend to produce?
a rapid response which may cause tumour lysis syndrome
443
Burkitt's lymphoma: what is usually given before chemo to reduce the risk of tumour lysis syndrome occuring?
Rasburicase (a recombinant version of urate oxidase, an enzyme that catalyses the conversion of uric acid to allantoin. Allantoin is 5-10x more soluble than uric acid so excretion is more effective)
444
Cx of tumour lysis syndrome? (5)
hyperkalaemia hyperphosphataemia hypocalcaemia hyperuricaemia acute renal failure
445
What is tumour lysis syndrome?
potentially life threatening Cx that occurs when ca cells break down rapidly, releasing intracellular contents into blood -> metabolic imbalances
446
What cancers is TLS most common in?
ones with high cell turnover eg. leukaemia and lymphoma, occasionally highly aggressive solid tumours
447
When does TLS commonly happen?
after initiating Tx for ca eg. chemo, radio or targeted which rapidly kill large no of tumour cells can occur spontaneous when ca cells die on own, esp in rapidly growing tumours
448
Symptoms of TLS?
Cardiac: Arrhythmias, palpitations, or even cardiac arrest (due to hyperkalemia). Renal: Acute kidney injury, leading to decreased urine output or complete kidney failure. Neurological: Muscle cramps, seizures, and altered mental status (due to electrolyte imbalances like hypocalcemia). Gastrointestinal: Nausea, vomiting, and diarrhea. General: Fatigue, weakness, and confusion.
449
Diagnosis of TLS?
Blood Tests: Monitoring of electrolyte levels (potassium, phosphate, calcium), uric acid, and kidney function (creatinine levels). Clinical Criteria: Based on the Cairo-Bishop classification, which includes both laboratory abnormalities and clinical manifestations like acute kidney failure or arrhythmias.
450
Mx and prevention of TLS?
Hydration: Aggressive IV fluids to help flush out toxins and prevent kidney injury. Allopurinol: Prevents the formation of uric acid by inhibiting xanthine oxidase. Rasburicase: Converts uric acid to allantoin, a more easily excretable compound, and is used in high-risk cases. Electrolyte Management: Hyperkalemia: May require insulin, glucose, or even dialysis to reduce potassium levels. Hypocalcemia: Treated cautiously, often with calcium supplements if symptomatic. Hyperphosphatemia: May require phosphate binders. Dialysis: In severe cases of kidney failure or life-threatening electrolyte disturbances.
451
Prognosis of TLS?
If managed quickly and appropriately, TLS can be controlled, but without timely intervention, it can lead to multi-organ failure and death.
452
What is crucial in high-risk pts for TLS?
Prevention is crucial in high-risk patients, and prophylactic measures (hydration, medications like allopurinol or rasburicase) are often initiated before starting cancer treatment.
453
RFs for TLS?
- ca type= rapidly proliferatng ca eg. ALL and high-grade lymphomas eg. Burkitt lymphoma - tumour burden= large tumour or extensive disease - high sensitivity to Tx= ca that respond quick to chemo - pre-existing kidney issues= exacerbate inability to handle large load of metabolic byproducts released during TLS
454
Example of a high grade lymphoma?
Burkitt's lymphoma
455
Malignant proliferation of lymphocytes characterised by the presence of Reed-Sternberg cell?
Hodgkin's lymphoma
456
Ages most affected by Hodgkin's lymphoma?
bimodal age distribution: 3rd and 7th decades most common
457
Histological classification of Hodgkin's lymphoma?
- Nodular sclerosing (70%) - Mixed cellularity (20%) - Lymphocyte predominant (5%) - Lymphocyte depleted (rare)
458
What histological type of Hodgkin's lymphoma has the best prognosis?
Lymphocyte predominant
459
What histological type of Hodgkin's lymphoma has the worst prognosis?
Lymphocyte depleted
460
What histological types of Hodgkin's lymphoma have a good prognosis?
Mixed cellularity and nodular sclerosing Lymphocyte predominant= best
461
What histological type of Hodgkin's lymphoma is more common in women and associated with lacunar cells?
Nodular sclerosing
462
What histological type of Hodgkin's lymphoma is associated with a large number of Reed-Sternberg cells?
Mixed cellularity
463
What implies a poor prognosis in Hodgkin's lymphoma?
- B symptoms - Lymphocyte depleted type - >45yrs - stage IV - Hb < 10.5 g/dl - lymphocyte count < 600/µl or < 8% - male - albumin < 40 g/l - white blood count > 15,000/µl
464
'B' symptoms?
weight loss >10% in last 6m fever >38ºC night sweats
465
RFs for Hodgkin's lymphoma?
HIV EBV
466
Features of Hodgkin's lymphoma?
- lymphadenopathy (75%) - systemic B symptoms (25%) - possible: mediastinal mass- may be symptomatic (cough) or incidental on CXR
467
Subtypes of ALL?
B-cell ALL (80%) T-cell ALL (20%)
468
Causes of ALL?
1) chemoradiation 2) genetic= Down's (ALL & AML) and translocations 3) infection
469
How may chemoradiation cause ALL?
cause mutations so increase DNA replication without lymphoblasts actually dying so not differentiating into T and B cells
470
Translocations that cause ALL?
(12:20)t= children (9:22)t= adults, Philidelphia chromosome forming BCR-ABL gene (different Tx for diff translocation)
471
What virus may cause T-cell ALL?
HTLV
472
What is associated with good prognosis in ALL?
hyperdiploid blast cells
473
Effects of increased lymphoblasts in bone marrow in ALL?
1) increased lymphoblasts -> decreased function WBC= increase risk of INFECTION & mortality eg. pneumonia, UTI, cellulitis 2) decrease RBC (less space in BM)= ANAEMIA so pallor, fatigue, SOB 3) decrease platelets (less space)= THROMBOCYTOPENIA= bruising- petechiae, purpura and bleeding (epistaxis, GI, gums) 4) increase lymphoblasts= expand bone marrow= BONE PAIN, limping
474
Effects of increased lymphoblasts in blood & tissues in ALL?
1) Hepatosplenomegaly= N&V, abdo fullness 2) Lymphadenopathy= painless, common, eg. cervical 3) Meninges= Meningeal Leukaemia (meningitis features) and CN palsy eg. CN6 (so can't abduct eye) 4) Testes= Testicular enlargement 5) If T-cell ALL= Thymic enlargement (thymus overlies heart so if enlarged can compress...): - trachea- SOB, stridor - oesophagus- dysphagia - superior vena cave- vein enlargement eg. neck
475
What types of leukaemia may result in leukostasis or TLS?
AML or ALL AML>>> for leukostasis
476
Diagnosis of ALL?
1) FBC and blood smear 2) Definitive diagnosis= bone marrow biopsy 3) immunophenotyping 4) genetic studies 5) Tests of infiltration: - CNS= CT/MRI, LP - testis= USS - thymus= CXR, CT chest (enlargement of thymus/mediastinum) - Liver/spleen= USS, CT abdo
477
What would FBC and blood smear show in ALL?
- decreased RBC and platelets - variable functional WBC (high or low) - blood smear= increased immature lymohoblasts
478
What would bone marrow biopsy show in ALL?
Increased lymphoblasts >20% (blast cell predominance)
479
Immunophenotyping for ALL?
Immunohistochemistry: - lymphoblasts high - Tdt +ve - mpo -ve Flow cytometry: - T-ALL= CD2-CD8 (CD3) - B-ALL= CD10,19,20
480
Genetic studies in ALL?
(12:21)t= children, more common (9:22)t= adults, Phil. chromosome Is it BCR-ABL +ve? If so and there is (9:22)t then Tx with tyrosine kinase inhibitors
481
Why is immunophenotyping and genetic studies done in ALL?
as different Tx for different translocations
482
Treatment for ALL?
1) systemic chemo: induction -> consolidation -> maintenance (phase). Goal= complete remission 2) prophylactic intrathecal chemotherapy with methotrexate +/- cranial radiotherapy 3) AND TLS prophylaxsis If fail... 4) Advanced therapies: - TKIs - Bone marrow Transplant
483
Systemic chemo agents for ALL?
C.yclophosphamide V.incristine A.sparaginase (+/-) D.oxorubicin D.examethasone (or pred)
484
Why is prophylactic intrathecal chemo with methatrexate +/- cranial radiation done in ALL?
risk of meningeal leukaemia in ALL
485
Advanced therapies for ALL if chemo fails?
- Tyrosine kinase inhibitors eg. imatinib - Bone marrow transplant if= fail chemo, fail TKIs and poor prognosis
486
When can tyrosine kinase inhibitors be used for ALL eg. imatinib?
if +ve for (9:22)t and BCR-ABL
487
Cx and explanation of ALL?
TLS Malignant cells hit with chemo, burst and release: - phosphates - uric acid - potassium so cause AKI
488
Prophylaxis for TLS eg. in ALL?
- IV fluids - Allopurinol - Rasburicase (all 3)
489
Causes of increased myeloblasts (stopping differentiation into granulocytes)? (eg. AML)
1) chemoradiation 2) Genetic 3) Bone marrow disorder
490
Genetic causes of increased myeloblasts? (eg. AML)
- Down's - AML subtype APL due to (15:17)t with PML-RARA gene
491
Bone marrow disorders than can cause increased myeloblasts (eg. in AML)?
1) Myelodysplastic syndrome -> progresses to AML 2) CML -> AML
492
Effects of increased myeloblasts in the bone marrow in AML?
1) increased myeloblasts so decrease functional WBCs (don't kill pathogens or differentiate to N, B or E)= Increased risk of infection and mortality eg. pneumonia, UTI, cellulitis 2) decrease RBC as less space= anaemia: pallor, fatigue, SOB 3) decrease platelets as less space= thrombocytopenia: bruising (petechiae, purpura), bleeding (gums, GI, nose) 4) increase myeloblasts= expands bone marrow= bone pain, limping
493
Effects of increased myeloblasts in blood and tissues in AML?
1) leukostasis (AML>>ALL) if >=100,000 myeloblasts 2) Tumour lysis syndrome 3) Cutaneous/mucosal= leukaemia cutis and gingival hyperplasia 4) DIC (only in APL)= increase bleeding risk
494
Leukostasis in AML?
if >=100,000 myeloblasts clog up blood flow due to blood vessel occlusion therefore: - hypoxaemia= headache, TIA, stroke - lungs= SOB, hypoxia so acute resp failure - retina= vision changes, vision loss
495
Tumour lysis syndrome in AML?
secondary to chemo (most common) or spontaneous secondary to high tumour burden myeloblasts burst releasing phosphate, K+ and uric acid causing AKI as uric acid forms crystals and phosphate combines with Ca to form crystals (kidney stones) causing damage to kidney SO get= low urine output, high creatinine, high BUN; high K+ can cause arrythmias
496
DIC in AML (only in APL subtype)?
myeloblast releases: 1) tissue factor (III) -> increase clotting pathway -> decrease clotting factors (secondary to consumption) so can't clot when need to 2) TPA -> fibrinolysis -> can't clot therefore increase bleeding risk: - brain bleed= ICH - bleed into lungs= pulmonary haemorrhage - bruising, bleeding (eg. out of cannula)
497
Diagnosis of AML?
1) FBC & blood smear 2) Definitive= bone marrow biopsy then to determine Tx and prognosis... 3) immunophenotyping 4) Genetic studies 5) Tests of Cx: - electrolyte panel if TLS - clotting screen if DIC - clinical exam if leukostasis or cutaneous/mucosal manifestations
498
What would FBC and blood smear show in AML?
- decreased RBC - decreased platelets - variable functional WBCs (increased or decreased) blood smear= increased myeloblasts and Auer rods (esp in APL)
499
Bone marrow biopsy in AML?
increased myeloblasts (>20%) Auer rods
500
Auer rods?
AML
501
Immunophenotyping in AML?
Immunohistochemistry: - mpo +ve (myloperoxodase) - Tdt -ve
502
Genetic studies in AML?
for subtypes and Tx (15:17)t= APL AML-RARA +ve= APL if APL then different Tx needed compared to other AML subtypes
503
Electrolyte panel if TLS in AML?
- high phosphate - high uric acid - high potassium - low Ca as combine with PO4- to form crystals - AKI so high creatinine and high BUN
504
Clotting screen if DIC in AML?
high PTT high INR high d-dimer low fibrinogen low RBCs low platelets
505
Tx for AML?
- systemic chemo for non-APL subtype - systemic chemo for APL subtype - Bone marrow transplant - Tx of Cx: leukostasis or TLS
506
Systemic chemo for AML (non-APL subtype)?
agents= Cytarabine and daunorubicin induction -> consolidation -> maintenance goal= complete remission
507
Systemic chemo for AML (APL subtype)?
agents= ATRA +/- arsenic trioxide; may give steroids to prevent differentiation syndrome good prognosis goal= promote differentiation: myeloblast -> promyelocyte -> granulocyte
508
What could chemo for APL subtype of AML lead to?
differentiation syndrome as goal if to promote differentiation (of undifferentiated high amounts of myeloblasts to granulocytes so good prognosis) this causes cytokine storm so can give steroids too to try prevent this
509
Bone marrow transplant in AML?
if: - AML with poor prognostic findings (likely to fail chemo) or - AML that failed chemo (didn't undergo complete remission)
510
Tx of leukostasis in AML?
1) cytoreduction= leukapheresis (take away myeloblasts blocking vessels) and hydroxyurea (reduce no. of myeloblasts) 2) then chemo
511
Prevention/Tx of TLS in AML?
- allopurinol + - rasburicase + - IV fluids
512
Why is allopurinol and rasburicase used in TLS?
Myeloblasts burst and release purines which convert to uric acid which then go to kidney to damage and cause AKI. Allopurinol prevents purines converting to uric acid. Rasburicase converts the uric acid into allantoin which is not toxic to kidney
513
Haemoptysis pathway?
Haemocytoblast (stem cell in bone marrow which differentiates...) into 1)Myeloid stem cells into 2) RBCs (using erythropoeitin), platelets (using TPO) or myeloblasts (CSF) 3) myeloblasts -> promylocyte 4) promylocyte -> neutrophil, basophil or eosinophil (all granulocytes) or 1) Lymphoid stem cells into 2) lymphoblast into 3) B lymphoblasts -> T-cells -> go to thymus and lymph nodes or 3) T lymohoblasts -> B-cells -> go to lymph nodes
514
Subtype of AML?
APL (Acute promyelocytic leukemia)
515
516
alcohol-induced lymph node pain?
Hodgkin's lymphoma
517
Lymphadenopathy in Hodgkin's lymphoma?
- common in neck (cericval/supraclavicular) > axillary > inguinal - usually painless, non-tender, asymmetrical - alcohol induced LN pain (<10% pts)
518
B symptoms in Hodgkin's lymphoma?
weight loss pruritus night sweats fever (Pel-Ebstein)
519
Ix for Hodgkin's lymphoma?
- normocytic anaemia - esosinophilia - LDH raised - Lymph node biopsy= Reed-Sternberg cells diagnostic
520
Normocytic anaemia in Hodgkin's lymphoma?
may be multifactorial eg. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia
521
What causes eosinophilia in Hodgkin's lymphoma?
production of cytokines eg. IL-5
522
What is diagnostic for Hodgkin's lymphoma?
Lymph node biopsy= Reed-Sternberg cells large cells; multinucleated or bilobed nucleus with eosinophilic inclusion-like nuclei (giving owl's eye appearance)
523
Reed-Sternberg cells seen in what?
Hodgkin's lymphoma
524
Old classification for Hodgkin's lymphoma?
Ann-Arbor staging Stage I: single lymph node II: 2 or more lymph nodes/regions on the same side of the diaphragm III: nodes on both sides of the diaphragm IV: spread beyond lymph nodes Each stage may be subdivided into A or B A = no systemic symptoms other than pruritus B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)
525
Classification used to stage Hodgkin's lymphoma (and other lymphomas)?
Lugano classification (updated version of Ann-Arbor) Stages I-IV; A/B, E, S and X
526
Stages in the Lugano classification for Hodgkin's lymphoma?
Stage I: invl. of a single lymph node region (I) or a single extralymphatic organ or site (IE). Stage II: invl. of 2 or more LN regions on the same side of the diaphragm (II) or localized involvement of an extralymphatic organ or site and one or more LN regions on the same side of the diaphragm (IIE). Stage III: invl. of LN regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE), involvement of the spleen (IIIS), or both (IIIE+S). Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement.
527
What else does the Lugano classification for Hodgkin's lymphoma in addition to the stages? (4)
A/B symptoms= no B symptoms then classed as A, if B symptoms then B E= presence of extranodal disease S= involvement of the spleen X= bulky disease (large tumour mass)
528
What does the Lugano classification system for Hodgkin's lymphoma emphasise the role of?
PET scans to determine staging- assess whether lymphoma is metabolically active in diff parts of body
529
Mx for Hodgkin's lymphoma?
- chemo -radiotherapy - combined modality therapy (CMT)= chemo followed by radio - hematopoeitic cell transplant= for relapsed or refractory classic Hodgkin lymphoma
530
What is combined modality therapy (CMT)?
chemotherapy followed by radiotherapy
531
2 combinations of chemotherapy that can be used for Hodgkin's lymphoma?
ABVD= standard BEACOPP= alternative with better remission rates but higher toxicity
532
ABVD chemo regimen for Hodgkin's lymphoma?
doxorubicin bleomycin vinblastine decarbazine
533
BEACOPP chemo regimen for Hodgkin's lymphoma?
bleomycin etoposide doxorubicin cyclophosphamide vincristine procarbazine prednisone
534
Cx of treatment for Hodgkin's lymphoma?
most pts achieve long-term survival free of HL secondary malignancies are a risk eg. solid tumours- breast, lung
535
Differences between Hodgkin's lymphoma vs Non-hodgkin's lymphoma?
- higher prevalence of NHL - older mean age of diagnosis of NHL - in NHL there is non-contigous, multicentric spread - in NHL extranodal invl. is common - HL= Reed-Sternberg cells; NHL= NO R-S cells
536
Lymphoma definition?
malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs
537
How is lymphoma classified?
Hodgkin's lymphoma= presence of Reed-Sternberg cells Non-Hodgkins= every other type of lymphoma that is not Hodgkin's; NO Reed-Sternberg cells
538
Non-hodgkin's lymphoma may affect what cells?
B or T cells further classified as high or low grade
539
What is more common: NHL or HL?
NHL
540
What age is usually affected by non-hodgkin's lymphoma?
typically elderly, >75yrs
541
RFs for Non-Hodgkin's lymphoma?
- elderly - caucasian - Hx of viral infection esp EBV - FHx - chemical agents (pesticides, solvents) - Hx of chemo or radio - Immunodeficiency (transplant, HIV, DM) - Autoimmune (SLE, Sjogren's, coeliac)
542
Symptoms of Non-Hodgkin's lymphoma?
- painless lymohadenopathy (non-tender, rubbery, asymmetrical) - constitutional/B symptoms - extranodal disease: gastric (dyspepsia, dysphagia, weight loss, abdo pain); bone marrow (pancytopenia, bone pain); lungs; skin; CNS (nerve palsies)
543
How to differentiate between HL and NHL?
biopsy and CP HL= can have alcohol induced LN pain B symptoms typically earlier in HL and later in NHL extra-nodal disease much MORE common in NHL
544
Signs of Non-Hodgkin's lymphoma?
- weight loss - lymohadenopathy (cervical, axillary, inguinal) - palpable abdo mass: hepatomegaly, splenomegaly, lymph nodes - testicular mass - fever
545
Ix for Non-Hodgkin's lymphoma?
Diagnostic= excisional node biopsy - CT chest, abdo, pelvis (staging) - HIV test (RF for NHL) - FBC and blood film - ESR (prognostic indicator) - LDH (prognostic indicator) - other if clinically indicated eg. LFTs if ?liver mets, PET CT, bone marrow biopsy (BM invl?), LP if neuro CP
546
Why may FBC and blood film be done for NHL? ESR? LDH?
FBC & blood film= may have normocytic anaemia; helpful to rule out other haem malignancy eg. leukaemia ESR= good prognostic indicator LDH= marker of cell turnover, useful prognostic indicator
547
Classification to stage NHL?
Lugano staging
548
Mx of NHL depends on what?
the sub-type
549
Mx for NHL?
typically watchful waiting, chemo or radio Rituximab is used in combination with conventional chemo regimens (eg. CHOP) for variety of NHL types - all pts= flu/pneumococcal vaccines - neutropenia= may need Abx prophylaxis
550
Example chemo regimen for NHL?
CHOP: cyclophosphamide doxorubicin (hydroxydaunorubicin) vincristine (Oncovin®) prednisolone
551
Cx of NHL?
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia Superior vena cava obstruction Metastasis Spinal cord compression Complications related to treatment e.g. Side effects of chemotherapy
552
Prognosis of NHL?
Low-grade non-Hodgkin's lymphoma has a better prognosis High-grade non-Hodgkin's lymphoma has a worse prognosis but a higher cure rate
553
When to consider a suspected ca pathway referral for NHL in adults?
present with unexplained lymphadenopathy or splenomegaly take into account associated features eg. fever, night sweats, SOB, pruritus, weight loss
554
When to consider a very urgent referral (appointment within 48hrs) for specialist assessment of NHL in children and young adults?
present with unexplained lymphadenopathy or splenomegaly take into account associated features eg. fever, night sweats, SOB, pruritus, weight loss
555
What referral do you use for NHL or HL if pt is 16-24yrs, adult or children/young adult?
either depending on age and local arrangements
556
Type of referrals for NHL or HL?
- adult= suspected ca pathway referral (within 2w) - children/young adult= very urgent (within 48hrs)
557
When to consider a suspected ca pathway referral for HL in adults?
presenting with unexplained lymphadenopathy take into account: fever, night sweats, SOB, pruritus, weight loss or alcohol-induced lymph node pain
558
When to consider a very urgent referral (appointment within 48hrs) for specialist assessment of HL in children and young adults?
presenting with unexplained lymphadenopathy. When considering referral, take into account any associated symptoms, particularly fever, night sweats, shortness of breath, pruritus, or weight loss.
559
Most aggressive form of malignant melanoma?
nodular other forms spread more slowly
560
Subtypes of melanoma?
1) Nodular 2) Superficial spreading 3) Lentigo maligna 4) Acral lentiginous
561
Melanoma: superfical spreading type?
70% of cases Typically= arms, legs, back & chest, young people Appearance= growing mole with diagnostic features
562
Melanoma: nodular type?
second commonest Sun-exposed skin, middle aged Red or black lump or lump which bleeds or oozes
563
Melanoma: lentigo maligna type?
less common chronically sun exposed skin, older people a growing mole with diagnostic features
564
Melanoma: acral lentiginous form?
rare form nails, palms or soles; people with darker skin pigmentation subungal pigmentation (Hutchinson's sign) or on palms or feet
565
Rare forms of melanoma?
desmoplastic melanoma, amelanotic melanoma, or melanoma arising in other parts of the body such as ocular melanoma.
566
Main diagnostic features and secondary features of melanoma?
The main diagnostic features (major criteria): - Change in size - Change in shape - Change in colour Secondary features (minor criteria) - Diameter >= 7mm - Inflammation - Oozing or bleeding - Altered sensation
567
Mx for melanoma?
- suspicious lesions= excision biopsy: do not biopsy in primary care if suspected or uncertain- refer! - once confirmed= determine whether re-excision of margins is required (Breslow thickness) - sentinel lymph node mapping, isolated limb perfusion and block dissection of regional lymoh node groups should be selectively applied
568
Margins of excision related to Breslow thickness for melanoma?
Lesions 0-1mm thick= 1cm Lesions 1-2mm thick= 1- 2cm (Depending upon site and pathological features) Lesions 2-4mm thick= 2-3 cm (Depending upon site and pathological features) Lesions >4 mm thick= 3cm
569
Most important factor in determining prognosis of pts with malignant melanoma?
the invasion depth of a tumour (Breslow depth)
570
Breslow depth and approximate 5yr survival for melanoma?
< 0.75 mm= 95-100% 0.76 - 1.50 mm= 80-96% 1.51 - 4 mm= 60-75% > 4 mm= 50%
571
Urgent suspected ca pathway referral for pigmented lesion ?melanoma?
The lesion has a weighted 7-point checklist score of 3 or more. Dermoscopy suggests melanoma. There are nail changes, such as a new pigmented line in the nail (especially if there is associated damage to the nail), or a lesion growing under the nail. They have a new persistent skin condition, especially if growing, pigmented, or vascular in appearance and the diagnosis is unclear. There is any doubt about the lesion. A biopsy has confirmed the diagnosis of malignant melanoma. Note: if a lesion is suspected to be melanoma, an excision in primary care should be avoided.
572
Most common tumour causing bone mets? (in descending order)
prostate breast lung
573
Most common sites for bone mets (in descending order)?
spine pelvis ribs skull long bones
574
Features of bone mets?
bone pain pathological fractures hypercalcaemia raised ALP
575
Lung mets are seen with what cancers?
breast colorectal renal cell bladder prostate
576
Cannonball mets?
multiple round well-defined lung secondaries most commonly seen with renal cell ca, may also occur 2 to choriocarcinoma and prostate ca
577
Clacification in lung mets?
uncommon except in chondrosarcoma or osteosarcoma
578
Metastatic disease of unknown primary: Ix for initial diagnostic phase?
All pts: - FBC, U&E, LFT, calcium, urinalysis, LDH - CXR - CT chest, abdomen and pelvis - AFP and hCG Specific pts: - myeloma screen (if lytic bone lesions) - endoscopy (?symptoms) - PSA (men) - CA125 (women with peritoneal malignancy or ascites) - Testicular US (men with germ cell tumours) - Mammography (features of breast ca)
579
For pts presenting with MUO (mets of unknown origin), diagnosis can be divided into 2 phases. Aim of inital phase is to perform most appropritate Ix efficiently to identify what?
1) primary site which will guide Tx or 2) non-epithelial malignancy, which can be Tx regardless of primary site or metastatic epithelial or neuro-endrocrien malignancy without an identifiable primary site (diagnosis of provisional CUP- carcinoma of unknown primary)
580
Example of non-epthelial malignancies? (can be treated regardless of primary site)
lymphoma other haem malignancies melanoma sarcoma germ-cell tumours
581
Metastatic disease of unknown primary: secondary diagnostic phase Ix (special Ix)?
- tumour markers (but always do AFP and hCG, PSA, CA125 in all pts if relevant) - upper and lower GI endoscopy - mammogram - MRI breast - PET CT eg. if present with cervical lymphadenopathy - Antibodies= CK7, CK20, TTF-1, PLAP, ER, PSA with adenocarcinoma of MUO - Flexible bronchoscopy with biopsy, brushings and washing= present with intrapulmonary nodules and unsuitbale for peercutaneous biopsy - Tissue sample for histology if MUO with ascites
582
Mx for MUO: what presentations may benefit from radical Tx?
- SCC invl. upper or mid neck nodes - adenocarcinoma invl. axillary nodes - SCC invl. inguinal nodes - solitary mets
583
Presentations of MUO with poor prognosis?
multiple mets incl. brain involvement- do not offer chemo unless clinical trial
584
When to offer pts chemo if they have confirmed carcinoma with unknown primary (CUP)?
confirmed CUP with clinical and/or laboratory features of a specific treatable syndrome and adequate performance status.
585
How are metastatic bone tumours described?
blastic lytic or mixed
586
What metastatic bone tumours have the lowest risk of spontaneous fractures?
osteoblastic metastatic disease lower risk compared to oestolytic lesions of similar size
587
What metastatic bone lesions are most prone to spontaneous fracture?
lesions affecting peritrochanteric region because of the loading forces at that site
588
Scoring system to stratify the risk of spontaneous fracture for bone mets of varying types?
Mirel Scoring system
589
Mirel scoring system: work out score points for each type?
1 point= upper extremity; blastic radiographic appearance; <1/3 width of bone invloved; mild pain 2 points= lower extremity; mixed; 1/3-2/3; moderate pain 3 points= peritrochanteric; lytic; >2/3; pain aggravated by function
590
Tx for metastatic bone lesions depending on the Mirel scoring system?
Score 9+= risk of fracture is impending (33%); Tx is prophylactic fixation Score 8= borderline risk; consider fixation Score 7 or less= not impending risk (4%); non-operative Mx
591
What to do if spinal mets are thought to be the cause of spinal cord compression pain?
urgent specialist advice within 24hrs; immediate advice if neuro features unless contraindicated (signif suspicion of lymphoma) offer all pt with met spinal cord compression a loading dose of 16mg of dexamethasone asap
592
Pts may present with spinal mets before developing metastaic spinal cord compression, so it is important to do what?
identify these pts early before any neuro symptoms develop
593
Symptoms and findings of spinal mets?
- unrelenting lumbar back pain - any thoracic or cervical back pain - worse sneezing, coughing or straining - nocturnal - associated with tenderness - wakes pt up at night
594
Spinal mets: what if any neuro features are present?
suspect spinal cord compression and act promptly without neuro features= whole spine MRI within 1w (whole spine imaged as pts commonly present with multi-level disease)
595
Another name for myeloma?
multiple myeloma (same thing)
596
Multiple myeloma?
progressive malignant disease characterised by proliferation of abnormal plasma cells in bone marrow and abnormal monoclonal immunoglobulins in the blood
597
What organs/systems does multiple myeloma afffect?
bones kidneys blood immune system
598
Multiple myeloma more common in what gender/age?
men increases with age
599
Prognosis of multiple myeloma?
usually incurable but can disease control can be achieved for several yrs
600
What is associated with a worse prognosis in multiple myeloma?
pt has high levels of serum beta-2 microglobin; high plasma cell count; diffuse multiple bone lesions; hypercalcaemia; very high levels of M protein in blood and urine; renal impairment
601
Cx of multiple myeloma?
- Pathological bone fractures. - Spinal cord compression. - Renal damage. - Hypercalcaemia. - Impaired resistance to infection. - Anaemia. - Bleeding disorders. - Hyperviscosity of the blood.
602
CP of multiple myeloma?
- bone pain, often lower back - fatigue - confusion, muscle weakness, constipation, thirst and polyuria (due to hypercalcaemia) - weight loss - recurrent infection - headache, visual disturbance, cognitive impairment, mucosal bleeding, SOB (due to hyperviscosity of blood) - sensory loss, paraesthesia, limb weakness, walking difficulty, sphincter disturbance (due to spinal cord compression) - occasionally asymptomatic
603
Occasionally multiple myeloma is asymptomatic, so how would it present?
with abnormalities on blood tests eg: - normochromic, normocytic anaemia - renal impairment - hypercalcaemia - raised ESR, plasma viscosity, serum protein or globulin
604
What to do if suspect multiple myeloma in pt over 60yrs with persistent bone pain, esp back, or unexplained fracture?
arrange FBC, serum Ca and plasma viscosity or ESR
605
What to do if suspect multiple myeloma in pt over 60yrs with hypercalcaemia or leukopenia and presentation consistent with possible myeloma?
arrange very urgent serum electrophoresis, serum-free light chain assay and Bence-Jones protein urine assessment (within 48hrs)
606
What to do if pt has plasma viscosity, ESR or incidental finding on bloods and presentation are consistent with possible myeloma?
Consider very urgent serum electrophoresis, serum-free light chain assay, and Bence-Jones protein urine assessment (within 48 hours)
607
What else should be done in pts who u suspect multiple myeloma?
consider additional Ix: peripheral blood film, serum urea, creatinine and electrolytes, liver function tests, and for people with bone pain, X-rays of symptomatic areas (to rule out pathological fractures).
608
Multiple myeloma: when to arrange urgent hospital admission?
- for people with symptoms of spinal cord compression - if Ix reveal moderate to severe hypercalcaemia (corrected Ca 3.01mmol/L or higher) or AKI
609
What to do if serum and/or urine protein electrophoresis suggest myeloma?
urgent referral to haematologist within 2w for further Ix to confirm
610
Tx for multiple myeloma depends on what?
age disease stage prognosis cormorbidities
611
What might the Tx of mutiple myeloma inclue?
Bisphosphonates to reduce bone disease and pain. eg. zolendronic acid Treatments for anaemia. eg. erythropoietin analogues or blood transfusion Chemotherapeutic drugs. High-dose drug therapy and stem cell transplantation. Immunomodulatroy drugs eg. thalidominde, lenalidomine and pomalidomide + DVT prophylaxis (aspirin or LMWH) Steroids eg. prednisolone or dexamthasone
612
Symptoms of hypercalcaemia eg. in myeloma?
bone pain, abdominal pain, depression, confusion, muscle weakness, constipation, thirst, and polyuria
613
Multiple myeloma may present with what?
pathological fractures and recurrent infection
614
Examination in myeloma?
may be normal Hepatomegaly — present in about 4% of people. Splenomegaly — present in about 1% of people. Lymphadenopathy — present in about 1% of people.
615
Differential diagnosis of multiple myeloma?
- depression - osteoarthritis - DM - polymyalgia rheymatica - MGUS - Waldenstrom's macroglobulinaemia - Osteosclerotic myeloma - AL amyloidosis - heavy chain disease - NHL - plasma cell leukaemia
616
Waldenstrom's macroglobulinaemia
Clinical features include hyperviscosity syndrome, organomegaly, and lymphadenopathy presenting in a person with an average age of 65 years. (differential for myeloma)
617
Amyloid light chain (AL) amyloidosis (differential for myeloma)?
Clinical features include fatigue, weight loss, hepatomegaly, macroglossia, chronic kidney disease, heart failure, postural hypotension, carpal tunnel syndrome, and peripheral neuropathy.
618
Heavy chain disease (differential for myeloma)?
Clinical features include weakness, fatigue, fever, lymphadenopathy and hepatosplenomegaly, with a portion of the immunoglobulin heavy chain in the serum and/or urine.
619
Plasma cell leukaemia (differential for myeloma)?
Clinical features include bone pain, fatigue, recurrent infection, mucosal bleeding, hypercalcaemia, renal impairment, hepatomegaly, and splenomegaly.
620
Osteosclerotic myeloma?
(polyneuropathy, organomegaly, endocrine disease, M protein in the blood, and skin lesions [POEMS] syndrome) Clinical features include marked polyneuropathy with widespread neurological involvement, hepatomegaly, splenomegaly, sclerotic bone lesions, endocrine disease which might manifest as gynaecomastia, M protein in the blood, and skin lesions.
621
Can serum/urine electrophoresis be negative in multiple myeloma?
in 1-5% who have a 'non-secretory' form of the disease that produces no serum M protein or urinary Bence-Jones protein.
622
Ix for myeloma?
Back pain/unexplained fracture= FBC, serum Ca, plasma viscosity or ESR Hypercalcaemia/leukopenia + CP consistent= Very urgent (within 48 hours) serum electrophoresis, serum-free light-chain assay, and Bence-Jones protein urine assessment. Additional to confirm: - peripheral blood film - serum urea, creatinine, electrolytes and LFTs - X-rays if bone pain
623
What may peripheral blood film show in multiple myeloma?
rouleaux (aggregations of red blood cells), which might suggest underlying paraproteinaemia.
624
Why may urea, creatinine, electrolytes and LFTs be done if suspect myeloma?
detect renal impairment, raised uric acid from increased tumour cell turnover, and to determine total protein concentration, which is usually raised in multiple myeloma.
625
Secondary care Ix to confirm multiple myeloma?
- immunofixation of serum & urine= confirm presence of paraprotein - bone marrow aspirate and trephine biopsy, with plasma cell phenotyping= confirm the presence of monoclonal plasma cells in the bone marrow. - MRI GOLD to confirm extent of myeloma bone disease; CT if contraindicaated -- Estimate tumour burden and prognosis= FISH analysis of bone marrow aspirate; Serum beta-2 microglobulin concentration; next-generation DNA sequencing.
626
How often should pt with multiple myeloma be reviewed by a haematologist?
Symptomatic (active)= at least every 3m Asymptomatic (smouldering)= every 3m for 1st 5yrs then depends on long-term stability of the disease
627
What should be avoided in pts with myeloma?
aminoglycosides due to risk of renal toxicity
628
Chemotherapeutic drugs for myeloma?
cyclosphoshamide, doxirubicin, carfilozmib, bortezombin or melphalan
629
When to suspect end-stage myeloma?
when symptoms become refractory to Tx Bone pain. Renal failure. Bone marrow failure. Infection — infection is a common cause of death in people with multiple myeloma. Increasing fatigue. Anorexia and weight loss. Changes in communication, deteriorating mobility or performance status, or social withdrawal.
630
Myeloma disease course?
difficult to predict, may go through multiple lines of Tx and experience periods of relapse and remission. after each line of Tx, chance of remission decreases movement from stable to late stage disease can be rapid
631
Myeloma arises due to what?
genetic mutations that occur as B-lymphocytes differentiate into mature plasma cells
632
Median age at presentation of myeloma?
70yrs
633
Mnemonic to remember multiple myeloma?
Old CRABBI Old= age at presentation C.alcium= hypercalcaemia R.enal impairment A.naemia B.leeding= thrombocytopenia B.one lytic lesions I.nfection= more susceptible other= amyloidosis (eg. macroglossia), carpal tunnel, neuropathy, hyperviscosity
634
Why do you get hypercalcaemia in myeloma?
increased osteoclastic bone resorption caused by local cytokines (eg. IL-1, tumour necrosis factor) released by myeloma cells also less commonly: impaired renal function, increased renal tubular calcium resabsorption and elevated PTH-rP levels
635
What can constipation, nausea, anorexia and confusion in myeloma be caused by?
hypercalcaemia
636
Why do you get renal damage/impairment in myeloma?
monoclonal production of immunoglobulins results in light chain deposition within the renal tubules causes renal damage which presents as dehydration and increasing thirst other causes in myeloma: amyloidosis, nephrocalcinosis, nephrolithiasis
637
Why do you get anaemia in myeloma?
bone marrow crowding suppresses erythropoiesis leading to anaemia fatigue and pallor
638
Why do pts with myeloma have increased risk of bleeding?
bone barrow crowding results in thrombocytopenia which puts pts at risk of bleeding and bruising
639
Why may pt get bone lytic lesions in myeloma?
bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates bone lytic lesions may present as pain (esp in back) and increases risk of pathological fractures
640
Why may pts with myeloma have increased susceptibility to infection?
a reduction in normal production of immunoglobulins
641
Summary of Ix for myeloma?
- bloods= FBC (anaemia), peripheral blood film (rouleaux formation), U&E (renal failure), bone profile (hypercalcaemia) - protein electrophoresis= raised conc of monoclonal IgA/IgG in serum; in urine they are known as Bence Jones proteins - bone marrow aspiration= plasma cells signif raised- confirms diagnosis - whole body MRI and X-rays. X-rays= 'rain drop skull' (random pattern of dark spots; very similar to pepperpot skull in hyperparathyroidism)
642
Diagnostic criteria for myeloma?
one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma. Major criteria: - Plasmacytoma (as demonstrated on evaluation of biopsy specimen) - 30% plasma cells in a bone marrow sample - Elevated levels of M protein in the blood or urine Minor criteria - 10% to 30% plasma cells in a bone marrow sample. - Minor elevations in the level of M protein in the blood or urine. - Osteolytic lesions (as demonstrated on imaging studies). - Low levels of antibodies (not produced by the cancer cells) in the blood.
643
What type of malignancy is a chronic relapsing and remitting and deemed incurable?
myeloma
644
Aims of Mx for myeloma?
control symptoms, reduce Cx and prolong survival
645
The combination of drugs used to treat myeloma (induction therapy) depends on what?
whether a patient may be suitable for autologous hematopoietic cell transplantation or not.
646
Autologous hematopoiectic cell transplantation for myeloma?
involves the removal of a patient's own stem cells prior to chemotherapy, which are then replaced after chemotherapy prolong both event-free and overall survival when compared with non-transplant strategies typically it is younger, healthier patients who are suitable for stem cell transplantation and rigorous chemotherapy regimes.
647
Is allogenic hematopoiectic cell transplant used in myeloma?
not commonly due to high rates of overall mortality and symptoms of graft-versus-host disease. It is currently only used as part of clinical trials when treating multiple myeloma.
648
Autologous vs allogeneic hematopoiectic cell transplant?
autologous= transplant from same person who will get the transplant allogenic= from someone else eg. matched relative or unrelated donor
649
Cx of myeloma and their Mx?
pain: treat with analgesia (using the WHO analgesic ladder) pathological fracture: zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly. infection= receive annual influenza vaccinations they may also receive Immunoglobulin replacement therapy. VTE prophylaxis fatigue= treat all possible underlying causes, if symptoms persist consider an erythropoietin analogue.
650
How many ca pts are affected by spinal cord compression?
up to 5%
651
Neoplastic spinal cord compression- most common type?
extradural compression- usually due to vertebral body mets
652
Neoplastic spinal cord compression is more common in pts with what ca?
lung, breast and prostate
653
Earliest and most common symptom of neoplastic spinal cord compression?
back pain may be worse lying down and coughing
654
Features of neoplastic spinal cord compression?
- back pain - lower limb weakness - sensory loss and numbness - neuro signs depend on level of lesion
655
Neoplastic spinal cord compression: lesions above L1 usually result in what?
UMN signs in legs and a sensory level
656
Neoplastic spinal cord compression: lesions below L1 usually result in what?
LMN signs in legs and perianal numbness
657
Neoplastic spinal cord compression: what happens to tendon reflexes?
tend to be increased below the level of the lesion and absent at the level of lesion
658
Ix for neoplastic spinal cord compression?
urgent (within 24hrs of presentation) whole MRI spine
659
Mx for neoplastic spinal cord compression?
high dose oral dexamethasone urgent oncology assessment to consider radiotherapy or surgery
660
Most common type of oesophageal ca?
adenocarcinoma
661
What pts are more likely to develop adenocarcinoma of the oesophagus?
those with Hx of GORD or Barrett's
662
Oesophageal ca: adenocarinoma vs squamous cell cancer epidemiology?
A= most common type in UK/US SCC= most common type in developing world
663
Oesophageal ca: adenocarinoma vs squamous cell cancer location?
A= lower third, near the gastroesophageal junction SCC= upper 2/3rds of oesophagus
664
Oesophageal ca: adenocarinoma vs squamous cell cancer RFs?
A= GORD; Barrett's; smoking; obesity SCC= smoking, alcohol, achalasia; Plummer-Vinson syndrome; diets rich in nitrosamines
665
Features of oesophageal ca?
- dysphagia (most common): progressive - anorexia and weight loss - vomiting - odynophagia, hoarseness, malaena, cough
666
Diagnosis of oesophageal ca?
- Upper GI endoscopy with biopsy - Endoscopic USS for locoregional staging - CT chest, abdo and pelvis for initial staging: laparoscopy can be used to detect occult peritoneal disease; FDG-PET CT may be used for occult mets if mets not seen on initial CT
667
Mx for operable disease (T1N0M0) in oesophageal ca?
surgical resection- most common procedure is Ivor-Lewis type oesophagectomy
668
Mx for oesophageal ca?
surgical resection if possible may need adjuvant chemo
669
Biggest challenge in surgical resection for oesophageal ca?
anastomotic leak, with an intrathoracic anastomosis resulting in mediastinitis
670
Types of ovarian ca?
Epithelial ca (90%)= serous, mucinous, endometroid, clear cell, transitional cell and squamous Non-epithelial (10%)= germ cell tumours, sex cord/stromal cell
671
Most common ovarian ca?
Serous epithelial ca
672
Secondary mets can occur in ovary, most commonly from where?
ca of endometrium, breast and GI tract
673
Where may ovarian ca spread?
intraperitoneal structures and organs (causing intestinal obstruction and cachexia), liver, para-aortic lymph nodes and the lungs (causing pleural effusions)
674
Lifetime risk of women being diagnosed with ovarian ca?
1 in 50
675
What reduces risk of ovarian ca?
- high no. of pregnancies - breastfeeding - COCP
676
When should you suspect ovarian ca in women (particularly if >50yrs)? (CP)
any persistent or frequent (>12x per month): - abdo distension (bloating) - feeling full (early satiety) and/or loss of appetite - pelvic or abdo pain - increased urinary urgency and/or frequency - symptoms suggestive of IBS within last 12m if >50yrs - unexplained symptoms: - weight loss - malaise or fatigue - change in bowel habit - abnormal or postmenopausal bleeding - GI symptoms= dyspepsia, nausea and bowel obstruction - SOB (due to pleural effusion)
677
What to do if suspect ovarian ca?
- exam abdo and pelvis - if normal then CA125
678
Suspect ovarian ca and exam of abdo and pelvis= ascites or pelvic/abdo mass that is not caused by uterine fibroids?
urgent referral
679
Suspect ovarian ca, exam normal so do CA125: what if serum CA125 conc is raised?
urgent USS of abdo and pelvis arranged and urgent referral if this is suggestive of ovarian ca if USS and CA125 suggest ovarian ca then perform CT pelvis and abdo to establish extent of disease; + thorax if indicated
680
Suspect ovarian ca, exam normal so do CA125: what if serum CA125 conc is normal, or raised with normal USS?
consider other causes of symptoms
681
Peak age for ovarian ca?
60yrs
682
Why does ovarian ca have poor prognosis?
due to late diagnosis
683
Where is often the site of origin of many 'ovarain ca'?
distal end of fallopian tube
684
RFs for ovarian ca?
- FHx= mutations of BRCA1 or BRCA2 gene - many ovulations= early menarche, late menopause, nulliparity eg. when have 'more' ovulations
685
What cancers have notoriously vague symptoms/non specific presentation so often diagnosed late?
ovarian
686
Abdo distension and bloating, abdo and pelvic pain, urinary symptoms eg. urgency, early satiety and diarrhoea?
?ovarian ca
687
What is classed as a raised CA125?
35 IU/mL or greater
688
What may increase CA125?
ovarian ca endometriosis menstruation benign ovarian cysts other conditions
689
Can CA125 be used for screening for ovarian ca in asymptomatic women?
NO not very specific
690
Diagnosis for ovarian ca?
difficult, usually involves diagnostic laparotomy
691
Mx for ovarian ca?
usually combination of surgery and platinum-based chemo
692
Prognosis of ovarian ca?
- 80% have advanced disease at presentation - 5yr survival is <35%
693
In women under 40yrs with suspected ovarian ca, measure what on top of CA125 to identify women who may not have epithelial ovarian ca?
AFP and beta-hCG
694
Confirmed ovarian ca after exam, raised CA125 and USS (then CT for extent); what to do next?
Confirm tissue diagnosis by histology by laparotomy or if surgery not been performed can use percutaneous image guided biopsy if feasible
695
Mx for early (stage I) ovarian ca?
1) retroperitoneal lymph node assessment + optical surgical staging (surgery- resection) 2) Adjuvant if high risk stage I disease (grade 3 or stage Ic)= 6 cycles of carboplatin
696
What does optical surgical staging in ovarian ca involve?
optical surgical staging involves= midline laparotomy; total abdo hysterectomy; bilateral salpingo-oophorectomy or infracolic omentectomy; biopsies of any peritoneal deposits, random biopsies of plevis and abdo peritoneal
697
Mx of advanced (stage II to IV) ovarian ca?
1) primary surgery= complete resection of all macroscopic disease 2) chemo after surgery (debulking surgery with adjuvant chemo) or chemo before and after (neoadjuvant chemo and interval debulking surgery)
698
Over 80% of pancreatic tumours are what?
adenocarcinoma
699
Where do adenocarcinomas of the pancreas typically occur?
head of the pancreas
700
Is pancreatic ca often diagnosed early or late?
late as non-specific
701
Pancreatic ca associations?
- age - smoking - DM - chronic pancreatitis (but alcohol is not independent RF) - hereditary non-polyposis colorectal carcinoma - multiple endocrine neoplasia - BRCA2 gene - KRAS gene mutation
702
Painless jaundice
pancreatic ca
703
Features of pancreatic ca?
- painless jaundice= pale stools, dark urine, pruritus, cholestatic LFTs - abdo masses: hepatomegaly, gallbladderm epigastric mass - non-specific: anorexia, weight loss, epigastric pain - loss of exocrine function eg. steatorrhoea - loss of endocrine function eg. DM - atypical back pain - migratory thrombophlebitis (Trousseaus sign)
704
What picture do LFTs show in pancreatic ca?
cholestatic LFTs
705
What abdo masses may be found in pancreatic ca (in descending order of frequency)?
- hepatomegaly= due to mets - gallbladder= Courvoisier's law - epigastric mass= from primary tumour
706
What is Courvoisier's law in pancreatic ca?
Courvoisier's law states that in the presence of painless obstructive jaundice, a palpable gallbladder is unlikely to be due to gallstones
707
What is Trousseau's sign/syndrome in pancreatic ca?
paraneoplastic syndrome that can be associated with pancreatic cancer Recurrent episodes of thrombophlebitis in the upper and lower limbs, thoracic and abdominal wall, and major blood vessels of the abdomen. Due to coagulopathy associated with underlying malignancy.
708
Ix for pancreatic ca?
- high-resolution CT scanning Ix of choice - can do USS 'double duct' sign on imaging
709
'Double duct' sign on imaging?
pancreatic ca presence of simultaneous dilation of the common bile and pancreatic ducts
710
Mx for pancreatic ca?
<20% suitable for surgery at time of diagnosis - Whipple's resection (pancreaticoduodenectomy)= for resectable lesions in head of pancreas - Adjuvant chemo following surgery - ERCP with stenting used for palliation
711
Side-effects of a Whipple's resection for pancreatic ca?
dumping syndrome and peptic ulcer disease
712
Dumping syndrome?
diarrhea, nausea, and feeling light-headed or tired after a meal, that are caused by rapid gastric emptying. Rapid gastric emptying is a condition in which food moves too quickly from your stomach to your duodenum. Cx of Whipple's
713
Common chemo drugs for pancreatic ca?
1 or more than 1 of: gemcitabine capecitabine fluorouracil (5FU) irinotecan oxaliplatin nab-paclitaxel (Abraxane) cisplatin
714
A pathological fracture occurs in...
abnormal bone due to insignificant injury
715
Causes of pathological fractures?
- metastatic tumours - bone disease= osteogenesis imperfecta; osteoporosis; metabolic bone disease; Paget's disease - local benign conditions= chronic osteomyelitis; solitary bone cyst - primary malignant tumours
716
Metastatic tumours that may cause pathological fractures?
breast lung thyroid renal prostate
717
Primary malignant tumours that may cause pathological fractures?
chondrosarcoma osteosarcoma Ewing's tumour
718
Red flags for breast ca?
lump, changes to skin or nipple, change in shape, discharge
719
Red flags for lung ca?
persitent cough, haemoptysis, chest pain, SOB, non-resolving LRTI
720
Red flags fro prostate ca?
nocturia, hesitancy, incomplete bladder emptying
721
Red flags for bowel ca?
PR bleeding, change in bowel habit, abdo pain, tenesmus
722
Red flags for ca (systemic symptoms)?
unexplained weight loss, fall in appetite, decreased energy levels, back pain, night sweats, unexplained anaemia, change in bowel habit (esp in elderly)
723
What is discussed at MDT for ca?
Presentation and age Comorbidities WHO Performance status – indicator of patient’s fitness Biopsy findings – endoscopy, histological type Radiological findings – CT, MRI, PET TNM staging for each tumour type : Tumour Nodes Metastases Radical or Palliative Intent? Surgical or Non Surgical Management? Treatment plan based on patient’s wishes Referral to appropriate team
724
Performance Status: ECOG/WHO?
0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
725
Non surgical oncology: what does curative/radical mean?
aim to cure
726
Non surgical oncology: what does neoadjuvant mean?
therapy given before surgery/radiotherapy to shrink cancer down, improve outcome of resection and reduce risk of recurrence
727
Non surgical oncology: what does adjuvant mean?
aimed at reducing risk of local recurrence or distant recurrence by treating micrometastatic disease can be chemo, radio, immuno ect.
728
Non surgical oncology: what goes palliative/disease control mean?
not curative, but aimed at improving quality of life and survival
729
Examples of systemic anti-cancer therapy?
- cytotoxic therapy - targeted therapy - endocrine therapy - immunotherapy - bisphosphonates
730
What does chemotherapy do?
multiple classes of agents all affect cell cycle in some way cytotoxic agents- cause cell death
731
Examples of endocrine Tx?
Tamoxifen and aromatase inhibitors for breast ca Prostate= GNRH analogues eg. zoladex
732
What are targeted therapies?
Act on different parts of the pathway/cascade which lead to cell proliferation, growth, transformation, angiogenesis and invasion Aim is to inhibit the pathway at various points to stop the stimulus to the cancer and cause apoptosis
733
What is immunotherapy?
using pts own immune system to kill ca caused activation of T cells that recognise and kill ca cells eg. ipilimumab for metastatic melanoma as lung ca autoimmune toxicities (colitis most common) which can be multisystem (as uses immune system)
734
What is radiotherapy?
Ionising radiation= xrays (or gamma rays); xrays can directly break DNA bonds used to damage ca cells, whose repair mechanisms are inadequate end result is cell death different dose depths dependent on energy
735
Principle of radiotherapy?
Use maximum dose for tumour control Whilst minimising dose to normal surrounding tissue
736
Radiotherapy techniques?
- IMRT - SABR
737
SABR (radiotherapy technique)?
Stereotactic ablative body radiotherapy: - Liver - Lung - Prostate - Oligometastases: lymph nodes, spine, adrenals, bone Precise irradiation with a higher radiation dose per fraction Highly conformal dose delivery with steep dose gradients Immobilisation - Passive - 4DCT, breathing control - Active - motion tracking, compression OARs
738
IMRT (radiotherapy technique)?
produce tightly conformal plans with concave structures; needs excellent immobolisation and image guidance to allow reduced margins and reduced dose to organs at risk, while maintaining or increasing doses to the tumour
739
General side effects of chemo?
fatigue, nausea and vomiting, mucositis, myelosuppression, sepsis, impact on renal and liver function, alopecia, taste change, unstable BMs, blood clots, infertility, allergic reactions Some chemo agents will have a greater risk of nephrotoxicity and cardiotoxicity
740
General side effects of immunotherapy?
can be multisystem inflammation, including endocrine disturbance. Usually treated with high dose steroids – SPEAK TO AOS team early
741
General side effects of radiotherapy?
LOCALISED treatment and side effects are dependent on the anatomical site being treated. Subdivided into acute and late side effects. (depends on structures around area trying to treat)
742
Mx for chemo side effects: N&V? (preventative/Mx)
Dexamethasone with chemo Granisetron iv (5-HT3 antagonist), PRN Ondansetron, metoclopramide Haloperidol and Levomepromazine if above fail IV fluids as needed
743
Mx for chemo side effects: diarrhoea? (preventative/Mx)
Really important to check it is not immunotherapy treatment first Loperamide, codeine – don’t always wait for MC&S stool Significant risk with 5FU/Capecitabine
744
Mx for chemo side effects: constipation? (preventative/Mx)
Esp. if on 5HT3 antagonists (ondansetron) Laxatives, enema Consider bowel obstruction
745
Mx for chemo side effects: stomatitis/mucositis? (preventative/Mx)
Difflam, Bioxtra gel, analgesia Mucositis
746
Mx for chemo side effects: other? (preventative/Mx)
5FU/Capecitabine can causes coronary spasm-chest pain/ bradycardias See UKONS for Ix and management.
747
Targeted agents exampoles and side effects?
nibs” Sunitinib Pazopanib Tivozanib SIDE EFFECTS ARE VARIED …all of them cause fatigue and GI toxicity Tyrosine Kinase Inhibitors – diarrhoea, HTN (some), hepatitis, hypothyroidism (some), QT prolongation, less likely bone marrow suppression(but may be if used in combination i.e. dabrafanib and trametinib)
748
Immunotherapy toxicity?
Hepatitis Nephritis Colitis Pneumonitis MYOCARDITIS Skin, joints Hypophysitis…. But can affect any organ
749
Mx of immunotherapy toxicity?
Grade 1 – observe/monitor Grade 2 – oral Pred 1mg/kg Grade 3- 4 – IV Methyl pred If already on steroids, go back up to previous dose; if not weaning d/w specialty of organ and start additional immunosuppression – MMF, Infliximab
750
Examples of oncology emergencies?
- Metastatic Spinal Cord Compression (MSCC) - Hypercalcaemia - SVC Obstruction - Seizure - Venous or Arterial - Thromboembolism - Pleural Effusion - Bowel Obstruction
751
What is neutropenic sepsis?
Sepsis with neutrophils <1.0 may present with fever alone, with no obvious source chemo hotline in all ca centres door to needle time <1hr ie to delivery of Abx early discussion with on call oncology team esp if organ failure high risk regimens- prophylactic GCSF
752
Pathogens in neutropenic sepsis?
Gram positive bacteraemia 70%: Staphylococcus aureus Coagulase-negative staphylococcus alpha and beta haemolytic streptococcus Gram negative bacteraemia 30%: Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Fungi: Candida , Aspergillus
753
Mx of neutropenic sepsis?
ABCDE Must be given the first dose of IV Abx within one hour of presentation  Do not wait for FBC or culture results before giving first dose. Piperacillin/Tazobactam (Tazocin) 4.5g QDS + Gentamicin (dose according to STHFT gentamicin chart) +/-  Vancomycin  -  if line infection suspected (as per vancomycin dosing guidelines) See local guidelines for penicillin allergy, renal impairment Need to know local Trust policy – not always the same AB
754
Assessment for neutropenic sepsis?
1) Temperature + observations + calculate Early Warning Score (NEWS)  2) Urgent bloods: FBC, Clotting, blood cultures (peripheral +/- CVAD), U&E, LFT, CRP and serum lactate. 3) Urgent medical review and clinical examination. Assess for symptoms and signs of infection. Assess any lines (e.g., Portacath, Hickman line) History: chemo and timings, allergies, previous episodes 4) Micro/virology specimens as clinically indicated (e.g. CVAD exit site, sputum, urine, throat swab). 5) CXR if respiratory symptoms, signs or hypoxia. 6) Consider septic shock and need for fluid challenge. (EARLY) 7) Monitor fluid balance but do not catheterise routinely due to risk of infection.  Do not routinely PR/PV – risk of bacteraemia 8) If Oxygen saturations less than 95% consider appropriate oxygen administration.
755
Neutropenic sepsis monitoring?
1)Monitor (NEWS) (4 hourly minimum, increase if indicated) 2) Record fluid intake and output  3) Arrange repeat blood tests including FBC, U&E’s, CRP + Gentamicin/Vancomycin levels if required. 4) Minimum once daily clinical team review Seek advice: 1) Discuss with senior member of the oncology on-call team (SpR or Consultant) via switch board or AOS team 2) Discuss and document appropriate level of escalation of care (e.g. HDU, active treatment on ward) 3) Discuss need for other treatments e.g. G-CSF. 
756
Malignant spinal cord compression summary?
Spinal cord ends at around L1 in adults Above this level – spinal cord compression Below this – cauda equina Can be caused by: Vertebral metastases Soft tissue mass Retropulsed bony fragment due to fracture WORSENING BACK PAIN is a LATE SIGN. Do NOT wait for the neurological deficit, especially in a patient known to have cancer
757
Typical history for spinal cord compression?
Back pain, radicular pain Common in prostate/breast/lung cancers Limb weakness – progressive, can be sudden Sensory level Bladder/bowel dysfunction Anal tone ↓
758
Diagnosis for spinal cord compression?
MRI WHOLE SPINE
759
Mx for spinal cord compression?
Once established neurology- 24h to surgery or radiotherapy - Steroids (dexamethasone 8mg BD with PPI and monitor BMs) - Same day MRI scan (including out of hours) - Urgent discussion with oncology and spinal surgeons - Surgical decompression/stabilisation vs radiotherapy
760
What electrolyte abnormality is common in advanced ca?
hypercalcaemia
761
Example of why you get hypercalcaemia in advanced ca?
bone mets production of ectopic PTHrp (parathyroid hormone related peptide) by ca- esp SCC
761
Mx of hypercalcaemia in ca?
rehydrate- manage AKI IV bisphosphonates (zolendronate, pamidronate) manage the cause if possible- treat the ca
762
Symptoms of hypercalcaemia in ca?
bones, moans, stones, abdo groans
763
Hypercalcaemia in ca is often associated with what?
AKI
763
What does the SVC provide?
the venous drainage for the head, neck, upper limbs and the upper thorax
764
What happens when SVC is obstructed?
collateral pathways form to provide an alternative route for blood to return to the right atrium
765
Causes of SVC obstruction?
- inside the vessel= thrombus or intravascular device - inside the vessel wall= direct tumour invasion - outside the vessel= tumour, lung ca, lymphoma
766
Symptoms of SVCO?
- dyspnoea - chest pain, often at rest - cough - neck and face swelling - arm swelling - others= dizziness, headache, visual disturbance, nasal stuffiness, syncope
767
Signs of SVCO?
- dilated veins over arms, neck and anteroir chest wall - oedema of upper torso, arms, neck and face - severe resp distress - cyanosis - engorged conjunctiva - convulsions and coma
768
Ix for SVCO?
- may be clinical diagnosis - CXR (widened mediastinum or mass on right side of heart) - May be incidental finding on CT - CTPA to define tumour extent, site of occlusion or stenosis and extent of any thrombus
769
Mx for SVCO?
- elevation of the head and oxygen therapy- symptomatic relief - high dose steroids if acute - endovascular stenting - consider: radio; chemo (esp in chemo-sensitive tumours eg small cell lung ca; anticoag if central vein thrombosis is present
770
Why are lots of pts with ca on dexamethasone or prednisolone?
- anti-inflamm/tumour effects: spinal cord compression, SVCO, brain mets (reduces oedema) ect - symptom control eg. appetite/sickness - immunotherapy related effects
771
What to do for all ca pts on steroids?
- always check if they were taking at admission - blood glucose monitoring QDS as inpatient for all - any pts discharged on steroids needs a BM monitoring kit - all pts need gastro-protection - refer to hyperglycaemia guidlines and do diabetic nurse referral on ICE if any issues with control/starting diabetes meds
772
Pt with ca complains of N/V, what to consider and Mx?
consider CAUSE chemo related= metoclopramide/ondansetron obstruction= avoid prokinetics, consider cyclizine/steroids instead, NBM, fluids, ryles tube brain mets= steroids, remeber metoclopramide CI in epilepsy, give alternative
773
In ca pts with N/V what antiemetics should you not prescribe together?
metoclopramide and cylixine DO NOT prescribe together
774
What antiemetics can be used in ca pts with N/V in difficult cases?
haloperidol, olanzapine, levomepromazine
775
What antiemetic is contraindicated in epilepsy?
metoclopramide
776
What might cause seizures in ca pts?
brain mets primary CNS ca
777
Mx for seizures in ca pts?
treat like any other- lorazepam if not self-terminating, commence keppra CT initially then MRI start steroids if known brain tumour, pending scan (8mg BD, reducing over next few days to 2-4mg per day depending on neuro symptoms) consider referral to neurosurgeons (refer a pt) and add to neuro oncology MDT
778
Electrolyte disturbances in ca pts may be secondary to what?
ca or Tx
779
Causes of hyponatraemic in ca pts?
tumour, recent steroids
780
Causes of hypercalcaemia in ca pts?
bone mets, SCC lung
781
Causes of hypocalcaemia in ca pts?
chemo, bisphosphonates, refeeding
782
Causes of hyperkalaemia in ca pts?
renal failure, tumour lysis syndrome
783
Causes of hypokalaemia in ca pts?
chemo, refeeding, diarrhoea
784
Causes of hypomagnasaemia in ca pts?
chemo, refeeding, EGFR inhibitor
785
Mx for replacement strategies for electrolyte disturbances in ca pts?
clinical guidelines
786
Suspected DVTs/PEs in ca pts?
- LOW THRESHOLD to consider doppler, CTPA - check clotting/platelets before LMWH - VTE referral - start LMWH in acute setting before switching to DOAC later (as some ca pts can't have DOACs
787
Some ca pts can't have what medication?
DOACs= GI infiltration, rectal tumours that are bleeding, varices
788
Ca pt with ascites?
if urgent, admit, US guided drain, check clotting (?does pt need restaging CT) if non urgent, can request as elective for future date malignant ascites can keep drain in for up to 30d, HAS not required
789
Any oncology emergency?
ask acute oncology team for advice
790
Prostate ca?
malignant tumour of prostate
791
Most cancers of the prostate (95%) are what?
adenocarcinomas
792
Prostate ca is multifocal, what does this mean?
the different foci may be caused by different genetic mutations, which can differ greatly in growth rate and ability to metastasize
793
Most prostate ca are slow or fast growing?
indolest and grow slowly- minority are aggressive and invade local structures or metastasise to remote tissues
794
Localised prostate ca usually develops where?
in outer zone of prostate where it rarely causes symptoms
795
Locally advanced prostate ca?
extends beyond the capsule of prostate and is often asymptomatic when diagnosed
796
Metastatic prostate ca mostly affects where?
bones- causes pain and fragility fractures
797
RFs for prostate ca?
age black ethnicity FHx
798
Symptoms of prostate ca?
unexplained... - lower back or bone pain - lethargy - erectile dysfunction - haematuria - anorexia/weight loss
799
Assessment of pt with suspected prostate ca?
- digital rectal exam (DRE) - prostate-specific antigen (PSA) test
800
Referral for suspected prostate ca?
suspected ca pathway= if prostate hard and nodular on DRE or benign enlargement consider suspected ca pathway if= PSA level above threshold for age (eg. >4.5 in pt 60-69yrs)
801
Mx for prostate ca?
- watchful waiting= older men, slowly progressing tumour, multiple co-morbidities, low Gleason score - Active surveillance= early prostate ca to avoid over treatment (as ca unlikely to cause harm). Involves prostate biopsy at intervals and PSA. Particularly suitable for men with clinical stage T1c, Gleason score 3+3 and PSA density < 0.15 ng/ml/ml who have cancer in less than 50% of their biopsy cores, with < 10 mm of any core involved. - Radical treatements= radical prostatectomy; external beam radiotherapy; or brachytheraoy - Adjunctive and palliative= hormone therapy; chemo (for hormone relapsed metastatic disease); bisphosphonates if taking androgen deprivation therapy and have osteoporosis
802
Examples of hormone treatments that can be used in prostate ca (removes and/or blocks effects of hormones which stimulate growth of prostate ca cells)?
- androgen deprivation (lowers testosterone)= bilateral orchidectomy or LHRH agonists eg. goserelin or antagonists eg. degarelix - androgen blockage= eg. cyproterone acetate, bind and block to hormone receptors of ca cells so preventing androgens stimualting growth
803
What does LHRH agonists stand for eg. goserelin?
luteninizing horomone releasing hormone agonists
804
Examples of chemo regimens for prostate ca?
- docetaxel + prednisolone - cabazitaxel + pred (2nd line) - 3rd line: dexamethasone
805
Mx of adverse effects of hormonal Tx in pt with prostate ca?
Hot flushes= medroxyprogesterone acetate 20mg od 10w Fatigue= supervised resistance and aerobic exercise twice a w for 12w Osteoporosis= bisphosphonates Gynaecomastia= if long-term bicalutamide monotherapy (>6m) refer for prophylactic radio to both breast buds within 1st month of Tx
806
Mx for sexual dysfunction in pt with prostate ca?
phosphodiesterase-5 (PDE-5) inhibitor eg. sildenafil
807
Ix for prostate ca?
- PSA - Digital rectal exam - multiparametric MIR (1st line) or trans rectal USS (+/-) biopsy (2nds line) - MRI/CT and bone scan for staging
808
How is prostate ca graded?
Gleason grading system, two grades awarded 1 for most dominant grade (on scale of 1-5) and 2 for second most dominant grade (scale 1-5). The two added together give the Gleason score. Where 2 is best prognosis and 10 the worst.
809
Lymphatic spread in prostate ca?
occurs first to the obturator nodes and local extra prostatic spread to the seminal vesicles is associated with distant disease.
810
Candidates for active surveillance in prostate ca Mx should...
have had at least 10 biopsy cores taken have at least one re-biopsy.
811
Features of prostate ca?
localised often asymptomatic - bladder outlet obstruction: hesitancy, urinary retention haematuria, haematospermia pain: back, perineal or testicular digital rectal examination: asymmetrical, hard, nodular enlargement with loss of median sulcus
812
Cx of TRUS biopsy eg. in suspected prostate ca?
sepsis: 1% of cases pain: lasting >= 2 weeks in 15% and severe in 7% fever: 5% haematuria and rectal bleeding
813
1st line Ix for suspected clinically localised prostate ca?
multiparametric MRI: results reported using a 5-point Likert scale
814
Likert scale in suspected prostate ca?
results from multiparametic MRI are reported using a 5-point Likert scale If the Likert scale is >=3 a multiparametric MRI-influenced prostate biopsy is offered If the Likert scale is 1-2 then NICE recommend discussing with the patient the pros and cons of having a biopsy.
815
Cx of radical prostatectomy?
erectile dysfunction
816
Adverse effects of radiotherapy for prostate ca?
develop proctitis and are also at increased risk of bladder, colon, and rectal cancer following radiotherapy for prostate cancer
817
How do GnRH agonists work for prostate ca Mx?
e.g. Goserelin (Zoladex) paradoxically result in lower LH levels longer term by causing overstimulation, resulting in disruption of endogenous hormonal feedback systems. The testosterone level will therefore rise initially for around 2-3 weeks before falling to castration leves initially therapy is often covered with an anti-androgen to prevent a rise in testosterone - 'tumour flare'. The resultant stimulation of prostate cancer growth may result in bone pain, bladder obstruction and other symptoms
818
Bicalutamide for prostate ca Mx?
non-steroidal anti-androgen blocks the androgen receptor
819
Cyproterone acetate for prostate ca Mx?
steroidal anti-androgen prevents DHT binding from intracytoplasmic protein complexes used less commonly since introduction of non-steroidal anti-androgens
820
Abiraterone for prostate ca?
androgen synthesis inhibitor option for the treatment of hormone-relapsed metastatic prostate cancer in patients who have no or mild symptoms after androgen deprivation therapy has failed, and before chemotherapy is indicated
821
Bilateral orchidectomy for prostate ca?
used to rapidly reduce testosterone levels
822
What is PSA?
serine protease enzyme produced by normal and malignant prostate epithelial cells
823
Age-specific PSA thresholds for people with possible symptoms of prostate ca?
40 Use clinical judgement 40–49 > 2.5 50–59 > 3.5 60–69 > 4.5 70–79 > 6.5 > 79 Use clinical judgement
824
What may also raise PSA levels?
- BPH - prostatitis and UTI (NICE recommend to postpone the PSA test for at least 6 weeks after treatment) - ejaculation (ideally not in the previous 48 hours) - vigorous exercise (ideally not in the previous 48 hours) - urinary retention - instrumentation of the urinary tract
825
What % of prostate ca will have normal PSA?
15%
826
Suspected testicular ca on clinical exam (or incidentially following USS of scrotum)?
urgent urology referral (using suspected ca pathway)
827
Consider arranging bloods for what at the time of referral for suspected testicular ca?
tumour markers= AFP, hCG, LDH
828
Most common malignancy in men 20-30yrs?
testicular
829
95% of testicular ca are what type of tumour?
germ-cell tumours
830
Types of germ cell tumours?
seminomas non-seminomas: including embryonal, yolk sac, teratoma and choriocarcinoma
831
Types of non-germ cell tumours?
Leydig cell tumours Sarcomas
832
Peak incidence for teratoma and seminomas?
T= 25yrs S= 35yrs
833
RFs for testicular ca?
- infertility (x3 increase risk) - cryptorchidism - FHx - Klinefelter's syndrome - mumps orchitis
834
Features of testicular ca?
- painless lump (most common) - pain (minority) - hydrocele - gynaecomastia
835
Why may pts get gynaecomastia?
due to increased oestrogen:androgen ratio germ-cell tumours → hCG → Leydig cell dysfunction → increases in both oestradiol and testosterone production, but rise in oestradiol is relatively greater than testosterone leydig cell tumours → directly secrete more oestradiol and convert additional androgen precursors to oestrogens
836
Tumour markers for germ cell tumours (testicular ca)?
seminomas= hCG may be elevated in 20% non-seminomas= AFP and/or beta-hCG elevated in 80-85% LDH elevated in 40% germ cell tumours
837
Diagnosis of testicular ca?
USS
838
Mx of testicular ca?
depends if tumour is seminoma or non-seminoma orchidectomy chemo and radio may be given depending on staging and tumour type
839
Prognosis of testicular ca?
generally excellent Seminomas= 5yrs survival 95% if stage I Teratomas= 85% if stage I
840
What are germ cell tumours?
group of tumours that originate from germ cells- cells responsible for developing into sperm or eggs germ cells normally migrate to gonads (testes/ovaries) during fetal development but can sometimes remain in other parts of body= potential for tumour development (reproductive organs and other areas)
841
Seminomas vs non-seminomas?
Seminomas and early-stage germ cell tumors= tend to have a high cure rate with appropriate treatment, often exceeding 90%. Non-seminomas, particularly those that are advanced or spread (metastatic), can be more challenging to treat but still have good outcomes with modern chemotherapy regimens.
842
Differential diagnosis for abdo swelling?
preg= young, female, amenorrhoea obstruction= Hx malignany/prev surgery; vomiting; not opened bowel recently; tinkling bowel sounds ascites= Hx of alcohol excess, cardiac failure urinary retention= Hx of prostate problems; dullness to percussion around suprapubic area ovarian ca= older female, pelvic pain, urinary symptoms (urgency), raised CA125, early satiety, bloating
843
Summary of breast fibroadenoma?
Develop from a whole lobule Mobile, firm, smooth breast lump - a 'breast mouse' 12% of all breast masses Over a 2 year period up to 30% will get smaller No increase in risk of malignancy If >3cm surgical excision is usual
844
Head and neck ca?
umbrella term, typically includes: - oral cavity ca - ca of the pharynx (incl oropharynx, hypopharynx, nasopharynx) - ca of the larynx
845
Features of head and neck ca?
neck lump hoarseness persistent sore throat persistent mouth ulcer
846
Consider suspected ca pathway referral for laryngeal ca in people...
aged 45yrs+ with: - persistent unexplained hoarseness or - unexplained lump in neck
847
Consider suspected ca pathway referral for oral ca in people with...
- unexplained ulceration in oral cavity lasting more than 3w or - persistent and unexplained lump in the neck
848
Consider urgent referral (within 2w) for assessment for possible oral ca by dentist in people who have...
- lump on the lip or in the oral cavity or - red or red and white patch in oral cavity consistent with erythroplakia or erythroleukoplakia
849
Consider suspected ca referral for thryoid ca in people with...
unexplained thyroid lump
850
Differential diagnosis for acute scrotal presentations in children?
testicular torsion= most common around puberty irreducible inguinal hernia= most common in children <2yrs epididymitis= rare in prepubescent children
851
Pathology of non seminomatous germ cell tumours?
heterogenous texture with occasional ectopic tissue such as hair
852
Pathology of seminomas?
Sheet like lobular patterns of cells with substantial fibrous component. Fibrous septa contain lymphocytic inclusions and granulomas may be seen.
853
Types of non seminomatous germ cell tumours?
Teratoma Yolk sac tumour Choriocarcinoma Mixed germ cell tumours (10%)
854
Key features of seminoma (type of germ cell tumour)?
Commonest subtype Average age at diagnosis = 40 Even advanced disease associated with 5 year survival of 73%
855
Key features of non seminomatous germ cell tumours?
Younger age at presentation =20-30 years Advanced disease carries worse prognosis (48% at 5 years) Retroperitoneal lymph node dissection may be needed for residual disease after chemotherapy
856
Tumour markers for seminoma?
AFP usually normal HCG elevated in 10% seminomas Lactate dehydrogenase; elevated in 10-20% seminomas (but also in many other conditions)
857
Tumour markers in non seminomas?
AFP elevated in up to 70% of cases HCG elevated in up to 40% of cases Other markers rarely helpful
858
Cell type in seminomas vs non-seminomas (NSGCTs)?
S= germ cells that are undifferentiated N-S= germ cells that are differentiated into various tissues
859
Seminomas vs non seminomas?
S= slow growing; may elevate b-hCG but normal AFP; highly sensitive to radio and chemo; excellent prognosis; subtypes= classic and spermatocytic seminoma N-S= faster growing & more aggressive; often elevated AFP and b-hCG; less sensitive to radio; treated with chemo; prognosis good but worse than S and varies with stage and subtype; sybtypes= embryonal carcinoma, yolk sac tumour, choriocarcinoma, teratoma
860
Examples of carcinogens and the cancer they may cause?
Aflatoxin (produced by Aspergillus)= Liver (hepatocellular carcinoma) Aniline dyes= Bladder (transitional cell carcinoma) Asbestos= Mesothelioma and bronchial carcinoma Nitrosamines= Oesophageal and gastric cancer Vinyl chloride= Hepatic angiosarcoma
861
RFs for developing N&V side effects of chemo?
- anxiety - <50yrs - concurrent use of opioids - type of chemo used
862
Drugs used for N&V in chemo pts?
low risk of N&V= metoclopramide high risk of symptoms= 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone
863
Cyclophosphamide?
alkylating agent used in the management of cancer and autoimmune conditions. It works by causing cross-linking of DNA
864
Adverse effects of cyclophosphamide?
haemorrhagic cystitis: incidence reduced by the use of hydration and mesna myelosuppression transitional cell carcinoma
865
Mesna?
2-mercaptoethane sulfonate Na a metabolite of cyclophosphamide called acrolein is toxic to urothelium mesna binds to and inactivates acrolein helping to prevent haemorrhagic cystitis
866
Examples of cytotoxic agents?
Alkylating agents= cyclophosphamide Cytotoxic antibodies= bleomycin, anthracyclines (eg. doxorubicin) Antimetabolites= methotrexate, fluorouracil (5-FU), 6-mercaptopurine, cytarabine Acts on microtubules= vincritine, vinblastine, docetaxel Topoisomerase inhibitors= irinotecan Other= cisplatin, hydroxyurea (hydroxycarbamide)
867
Cytotoxic agents: alkylating agents= cyclophosphamide MOA and adverse effects?
Alkylating agent - causes cross-linking in DNA Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma
868
Cytotoxic agents: cytotoxic antibodies= bleomycin MOA and adverse effects?
Degrades preformed DNA Lung fibrosis
869
Cytotoxic agents: cytotoxic antibodies= anthracyclines (eg. doxorubicin) MOA and adverse effects?
Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis Cardiomyopathy
870
Cytotoxic agents: antimetabolites= methotrexate MOA and adverse effects?
Inhibits dihydrofolate reductase and thymidylate synthesis Myelosuppression, mucositis, liver fibrosis, lung fibrosis
871
Cytotoxic agents: antimetabolites= fluorouracil (5-FU) MOA and adverse effects?
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase) Myelosuppression, mucositis, dermatitis
872
Cytotoxic agents: antimetabolites= 6-mercaptopurine MOA and adverse effects?
Purine analogue that is activated by HGPRTase, decreasing purine synthesis Myelosuppression
873
Cytotoxic agents: antimetabolites= cytarabine MOA and adverse effects?
Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase Myelosuppression, ataxia
874
Cytotoxic agents: acts on microtubules= vincristine, vinblastine MOA and adverse effects?
Inhibits formation of microtubules Vincristine: Peripheral neuropathy (reversible) , paralytic ileus Vinblastine: myelosuppression
875
Cytotoxic agents: acts on microtubules= docetaxel MOA and adverse effects?
Prevents microtubule depolymerisation & disassembly, decreasing free tubulin Neutropaenia
876
Cytotoxic agents: topoisomerase inhibitors= irinotecan MOA and adverse effects?
Inhibits topoisomerase I which prevents relaxation of supercoiled DNA Myelosuppression
877
Cytotoxic agents: other= cisplatin MOA and adverse effects?
Causes cross-linking in DNA Ototoxicity, peripheral neuropathy, hypomagnesaemia
878
Cytotoxic agents: other= hydroxyurea (hydroxycarbamide) MOA and adverse effects?
Inhibits ribonucleotide reductase, decreasing DNA synthesis Myelosuppression
879
Li-Fraumeni Syndrome?
- Autosomal dominant - Consists of germline mutations to p53 tumour suppressor gene - High incidence of malignancies particularly sarcomas and leukaemias - Diagnosed when: *Individual develops sarcoma under 45 years *First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age
880
BRCA 1 and 2?
- Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2) - Linked to developing breast cancer (60%) risk. - Associated risk of developing ovarian cancer (55% with BRCA 1 and 25% with BRCA 2). - BRCA2 mutation is associated with prostate cancer in men
881
Lynch Syndrome?
Autosomal dominant Develop colonic cancer and endometrial cancer at young age 80% of affected individuals will get colonic and/ or endometrial cancer High risk individuals may be identified using the Amsterdam criteria
882
Amsterdam criteria?
Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two. Two successive affected generations. One or more colon cancers diagnosed under age 50 years. Familial adenomatous polyposis (FAP) has been excluded.
883
Gardners syndrome?
Autosomal dominant familial colorectal polyposis Multiple colonic polyps Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts Desmoid tumours are seen in 15% Mutation of APC gene located on chromosome 5 Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer Now considered a variant of familial adenomatous polyposis coli
884
What is PET?
Positron Emission Tomography (PET) is a form of nuclear imaging which uses fluorodeoxyglucose (FDG) as the radiotracer. This allows a 3D image of metabolic activity to be generated using glucose uptake as a proxy marker. The images obtained are then combined with a conventional imaging technique such as CT to decide whether lesions are metabolically active. Uses - evaluating primary and possible metastatic disease
885
Tumour markers may be divided into what?
- monoclonal antibodies against carbohydrate or glycoprotein tumour antigens - tumour antigens - enzymes (alkaline phosphatase, neurone specific enolase) - hormones (e.g. calcitonin, ADH)
886
What tumour markers are monoclonal antibodies?
CA 125 CA 19-9 CA 15-3
887
What tumour markers are tumour antigens?
PSA AFP CEA S-100 Bombesin
888
Tumour markers: CA 125 association?
ovarain ca endometriosis, PID, menstruation, pregnancy
889
Tumour markers: CA 19-9 association?
pancreatic ca, gallbladder ca gallstones, pancreatitis, liver disease
890
Tumour markers: CA 15-3 association?
breast ca benign breast conditions, liver disease
891
Tumour markers: prostate specific antigen (PSA) association?
prostate ca BPH, prostatitis
892
Tumour markers: Alpha-feto protein (AFP) association?
hepatocellular carcinoma, testicular ca, teratoma pregnancy, liver cirrhosis, hepatitis
893
Tumour markers: Carcinoembryonic antigen (CEA) association?
colorectal ca also breast, lung, pancreatic ca smoking, IBD, liver disease
894
Tumour markers: S-100 association?
melanoma schwannomas
895
Tumour markers: bombesin association?
small cell lung carcinoma gastric ca neuroblastoma
896
Tumour markers: hCG?
testicular ca, choriocarcinoma pregnancy
897
Tumour markers: lactate dehydrogenase (LDH)?
lymphoma, leukaemia, testical ca general tissue damage, HF, anaemia, infections
898
Tumour markers: thyroglobulin?
thyroid ca thyroiditis, goiter
899
What are tumour markers?
often proteins produced by body in response to ca or by ca itself found in blood, urine or tissue can help diagnosis, monitor, prognosis of ca most aren't exclusive to ca not specific or sensitive enough so used in conjunction with other diagnostic tools eg. imaging and biopsy
900
Most common cause for hepatocellular carcinoma (HCC)
chronic hep B worldwide chronic hep c in europe
901
Main RF for developing HCC?
liver cirrhosis, eg. secondary to hep B & C, alcohol, haemochromatosis and primary biliary cirrhosis Wilson's is the exception
902
RFs for HCC?
liver cirrhosis chronic hep B & C alcohol haemochromatosis primary biliary cirrhosis alpha-1 antitrypsin deficiency hereditary tyrosinosis glycogen storage disease aflatoxin drugs: oral contraceptive pill, anabolic steroids porphyria cutanea tarda male sex diabetes mellitus, metabolic syndrome
903
Features of HCC?
- tends to present late - features of liver cirrhosis/failure= jaundice, ascites, RUQ pain, hepatomegaly, pruritus, splenomegaly - possible presentation is decompensation in pt with chronic liver disease - raised AFP
904
What should be considered for high risk groups for HCC?
screening with USS (+/- alpha-fetoprotein)
905
Examples of pts who are high risk for HCC and may have screening with ultrasound (+/- alpha-fetoprotein)?
- pts with liver cirrhosis secondary to hep B&C or haemochromatosis - men with liver cirrhosis secondary to alcohol
906
Mx options for HCC?
early disease: surgical resection liver transplantation radiofrequency ablation transarterial chemoembolisation sorafenib: a multikinase inhibitor
907
Do pts with thyroid ca get features of hyper or hypothyroidism?
not commonly as they rarely secrete thyroid hormones
908
Type of thyroid ca?
- papillary (70%) - follicular (20%) - medullary (5%) - anaplastic (1%) - lymohoma (rare)
909
What type of thyroid ca has an excellent prognosis and is often in young females?
papillary
910
What is medullary thyroid ca?
ca of parafollicular (C) cells, secrete calcitonin, part of MEN-2
911
What type of thyroid ca is not responsive to treatment and can cause pressure symptoms?
anaplastic
912
What type of thyroid ca is associated with Hasimoto's thyroiditis?
lymphoma thyroid ca
913
Mx of papillary and follicular ca?
- total thyroidectomy - followed by radioiodine (I-131) to kill residual cells - yearly thyroglobulin levels to detect early recurrent disease
914
Thyroid ca: papillary carcinoma?
Usually contain a mixture of papillary and colloidal filled follicles Histologically tumour has papillary projections and pale empty nuclei Seldom encapsulated Lymph node metastasis predominate Haematogenous metastasis rare
915
Thyroid ca: follicular adenoma?
Usually present as a solitary thyroid nodule Malignancy can only be excluded on formal histological assessment
916
Thyroid ca: follicular carcinoma?
May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma. Vascular invasion predominates Multifocal disease raree
917
Thyroid ca: medullary carcinoma?
C cells derived from neural crest and not thyroid tissue Serum calcitonin levels often raised Familial genetic disease accounts for up to 20% cases Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
918
Thyroid ca: anaplastic carcinoma?
Most common in elderly females Local invasion is a common feature Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.
919
Penile ca?
rare malignancy that affects the penis
920
How does penile ca typically present?
painless lesion or ulcer on glans or foreskin may get discharge or bleeding
921
RFs for penile ca?
phimosis poor hygiene smoking HPV infection
922
Diagnosis of penile ca?
biopsy and histopathological exam of lesion
923
Mx of penile ca?
depends on stage surgery, radio, chemo or combination
924
CP of penile ca?
painless penile lesion or ulceration, which may be accompanied by bleeding or discharge. - Changes in the colour or texture of the skin on the penis - Thickening or nodularity of the penile skin - Enlargement of regional lymph nodes - Erectile dysfunction or difficulty urinating - The location and size of the lesion may vary, with the glans and foreskin being the most commonly affected sites.
925
Consider suspected ca referral for penile ca in men if they have what?
either - a penile mass or ulcerated lesion, where a sexually transmitted infection has been excluded as a cause, or -a persistent penile lesion after treatment for a sexually transmitted infection has been completed, or - unexplained or persistent symptoms affecting the foreskin or glans
926
Follow up for pt with prostate ca being managed with watchful waiting?
- PSA at least once per yr -DRE not recommended on routine basis
927
Follow up for pt with prostate ca who are being managed with active surveillance
In year 1 of active surveillance: - Every 3–4 months: measure prostate-specific antigen. - Throughout active surveillance: monitor PSA kinetics (could include PSA density and velocity). - At 12 months: perform a DRE. - At 12–18 months: multiparametric MRI. In year 2 and every year thereafter until active surveillance ends: - Every 6 months: measure PSA. - Throughout active surveillance: monitor PSA kinetics (could include PSA density and velocity). - Every 12 months: perform a DRE. If there is concern about clinical or PSA changes at any time during active surveillance, the person should be reassessed with multiparametric MRI and/or re-biopsy.
928
People with localized prostate cancer who have chosen watchful waiting and who have evidence of significant disease progression (that is, rapidly rising PSA level or bone pain) should what?
have their situation reviewed by uro ca specialist
929
Follow up for pt with prostate ca who are being managed with radical treatment?
PSA levels should be measured no earlier than 6 weeks after treatment, then at least every 6 months for 2 years, and once a year thereafter. After at least 6 months' initial follow up, consider a remote follow-up strategy for people with a stable PSA who have had no significant treatment complications, unless they are taking part in a clinical trial that needs formal clinic-based follow up. Do not routinely offer DRE to people with localized prostate cancer who are not on active surveillance while their PSA remains at baseline levels.
930
Tumour lysis syndrome?
potentially deadly condition related to the treatment of high-grade lymphomas and leukaemias. It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy. On occasion, it can occur with steroid treatment alone. Awareness of the condition is critical as prophylactic medication can be given to prevent the potentially deadly effects of tumour cell lysis.
931
Why does tumour lysis syndrome (TLS) occur?
occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell. It leads to a high potassium and high phosphate level in the presence of a low calcium. It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.
932
Prevention for tumour lysis syndrome?
IV fluids patients are higher risk should receive either allopurinol or rasburicase rasburicase= a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys generally preferred now for patients at a higher risk of developing TLS allopurinol= generally used for patients in lower-risk groups rasburicase and allopurinol should not be given together in the management of tumour lysis syndrome as this reduces the effect of rasburicase
933
How is tumour lysis syndrome graded?
LS has been graded using the Cairo-Bishop scoring system: Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy: uric acid > 475umol/l or 25% increase potassium > 6 mmol/l or 25% increase phosphate > 1.125mmol/l or 25% increase calcium < 1.75mmol/l or 25% decrease
934
Clinical tumour lysis syndrome?
laboratory tumour lysis syndrome plus one or more of the following: increased serum creatinine (1.5 times upper limit of normal) cardiac arrhythmia or sudden death seizure
935
Bone sarcomas?
osteosarcoma chondrosarcoma Ewing's sarcoma
936
Soft tissue sarcomas?
Liposarcoma Rhabdomyosarcoma (striated muscle origin) Synovial sarcoma Fibrosarcoma Angiosarcoma Leiomyosarcoma (smooth muscle origin))
937
Presentations of sarcoma?
- pain - swelling or palpable mass (soft tissue>bone) - impaired function - pathologic fractures (bone) - systemic symptoms
938
Ix for sarcoma?
X-ray, CT, MRI, PET biopsy= fine needle aspiration, core needle biopsy or incisional biopsy for histopath
939
Mx for sarcomas?
- surgery= limb-sparing or amputation - radio= neoadjuvant or adjuvant or intraoperative radiation therapy (IORT) - chemo - Targeted therapy: For specific sarcoma subtypes, such as GIST, targeted therapy with tyrosine kinase inhibitors (e.g., imatinib)
940
941