Cancer Flashcards
Referral recommendation for skin lesion suspected of a basal cell carcinoma?
- 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
When to refer pt using suspected ca pathway referral (appointment within 2w) for melanoma?
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
Pigmented lesion on the skin?
?melanoma
Can get what type of melanomas rarely?
nodular and amelanotic
What checklist is used to assess pigmented skin lesions?
7-point checklist
Melanoma may present when?
after spread to regional lymph nodes or wider mets
Main method to diagnose melanoma?
excision biopsy in secondary care
Raised lesion on skin?
?SCC
Diagnose SCC?
possible to visually but confirm by excision biopsy
Ulcer with raised rolled edge; prominent fine blood vessels around a lesion or nodule on the skin (pearly or waxy)?
Basal cell carcinoma
Diagnosis of BCC?
possible visually but confirm by excision biopsy
7-point checklist for suspected melanoma?
Major (2 points each):
- change in size
- irregular shape
- irregular colour
Minor (1 each):
- largest diameter 7mm+
- inflam
- oozing
- change in sensation
Most common type of ca in Western world?
BCC
BCC characteristics?
- lesions also called Rodent ulcers
- slow growth
- local invasion
- mets v rare
Most common type of BCC?
nodular
Nodular BCC?
- sun exposed sites eg. head, neck
- initially= pearly, flesh coloured papule with telangiectasia
- later= ulcerate leaving central crater
Mx options for BCC?
- surgical removal
- curettage
- cryotherapy
- topical cream= imiquimod, fluorouracil
- radiotherapy
Bladder ca commonly affects who?
males 50-80yrs
RFs for bladder ca?
- male
- current or previous (within 20yrs) smokers
- exposure to hydrocarbons eg. 2-Napthylamine
- chronic bladder inflam from Schistosomiasis infection= SCC
-rubber manufacture - cyclophosphamide
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?
bladder ca
examples of benign tumours of the bladder? (uncommon)
- inverted urothelial papilloma
- nephrogenic adenoma
Examples of bladder malignancies?
- Urothelial (transitional cell) carcinoma (>90%)
- SCC (1-7% expect is higher in regions affected by schistosomiasis- rare in UK)
- Adenocarcinoma
Most common bladder malignancy?
urothelial (transitional cell) carcinoma (>90%)
Urothelial carcinomas may arise as what?
solitary lesions or may be multifocal causing ‘field change’ within the urothelium
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
Those with T3 disease or worse in urothelial carcinoma have a 30%+ risk of what?
regional or distant lymph node metastasis
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
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
Painless macroscopic haematuria?
?bladder ca
CP of bladder ca?
- painless marcoscopic haematuria
- incidential microscopic haematuria= 10% females >50yrs found to have malignancy after infection excluded
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
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
Prognosis of bladder ca?
T1 90%
T2 60%
T3 35%
T4a 10-25%
Any T, N1-N2 30%
How is cancer classified into types?
based on origin and characteristics of the abnormal cells
Carcinoma definition?
arises from epithelial cells that line internal organs and external surfaces
Types of carcinoma?
- adenocarcinoma
- SCC
- BCC
- transitional cel carcinoma
Most common types of cancer?
carcinoma
Types of carcinoma: adenocarcinoma definition?
develops in glandular tissues eg. breast, prostate, colon, pancreas
Types of carcinoma: SCC definition?
found in squamous cells eg. skin or lining of organs, for example lungs, oesophagus
Types of carcinoma: BCC definition?
form of skin cancer that starts in the basal cells
Types of carcinoma: transitional cell carcinoma definition?
arises in lining of the bladder, ureters and renal pelvis
Sarcoma definition?
develops in connective or supportive tissues such as bone, muscle, fat, cartilage and blood vessels
less common than carcinomas but more aggressive
Types of sarcoma?
- osteosarcoma
- chondrosarcoma
- liposarcoma
- leiomyosarcoma
Types of sarcoma: osteosarcoma definition?
originates in bone
Types of sarcoma: chondrosarcoma definition?
arises in cartilage
Types of sarcoma: liposarcoma definition?
develops from fat tissue
Types of sarcoma: leiomyocarcoma definition?
develops in smooth muscle tissue
Leukemia definition?
cancers of the blood-forming tissues, incl. bone marrow and lymphatic system
Types of leukemia?
- Acute Lymphoblastic Leukemia (ALL)
- Acute Myeloid Leukemia (AML)
- Chronic Lymphocytic Leukemia (CLL)
- Chronic Myeloid Leukemia (CML)
Types of leukemia: Acute Lymphoblastic Leukemia (ALL) definition?
affects lymphoid cells, common in children
Types of leukemia: Acute Acute Myeloid Leukemia (AML) definition?
affects myeloid cells, more common in adults
Types of leukemia: Chronic Lymphocytic Leukemia (CLL) definition?
slow-growing form affecting lymphoid cells
Types of leukemia: Chronic Myeloid Leukemia (CML) definition?
affects myeloid cells, progresses slowly
Lymphoma definition?
ca of the lymphatic system, which is part of the immune system
relatively common, esp non-Hodgkin
Types of lymphoma?
- Hodgkin Lymphoma (Hodgkin’s disease)
- Non-Hodgkin Lymphoma (NHL)
Types of lymphoma: Hodgkin Lymphoma definition?
characterised by presence of Reed-Sternberg cells
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
Myeloma definition?
ca of plasma cells, type of WBC in bone marrow
rare form of ca, affects mainly older adults
Type of myeloma?
multiple myeloma
Type of myeloma: multiple myeloma definition?
most common form, affecting many areas of body incl. bones and kidneys (Old CRAB)
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
Types of melanoma?
- cutaneous melanoma
- ocular melanoma
Types of melanoma: cutaneous melanoma definition?
starts in skin
Types of melanoma: ocular melanoma?
rare form that starts in the eye
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
Common types of CNS cancers?
- glioblastoma
- astrocytoma
- meningioma
Types of CNS cancers: glioblastoma definition?
highly aggressive form of brain cancer
Types of CNS cancers: astrocytoma definition?
originates in star-shaped brain cells called astrocytes
Types of CNS cancers: meningioma definition?
affects meninges, the protective layers around brain and spinal cord
Germ Cell tumours definition?
arises from the cells that give rise to sperm or eggs (germ cells)
most common in adolescents and young adults
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
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
Types of neuroendocrine tumours?
- carcinoid tumours
- pheochromocytoma
Types of neuroendocrine tumours: carcinoid tumours?
type of neuroendocrine tumour commonly found in GI tract and lungs
Types of neuroendocrine tumours: pheochromocytoma?
typically arises in adrenal glands
Blastoma definition?
typically arises in embryonic tissue or immature cells, usually seen in children
Common types of blastoma?
- retinoblastoma
- neuroblastoma
- hepatoblastoma
Common types of blastoma: retinoblastoma definition?
ca of the retina, typically in young children
Common types of blastoma: hepatoblastoma definition?
rare liver ca in children
Common types of blastoma: neuroblastoma definition?
starts in immature nerve cells, often in adrenal glands
Mesothelioma definition?
rare ca that affects lining of lungs, abdo or heart; often linked to asbestos exposure
Thyroid ca definition?
ca that forms in thyroid gland, with types like papillary, follicular, medullary and anaplastic thyroid ca
Types of cancers?
- carcinoma
- sarcoma
- leukemia
- lymphoma
- myeloma
- melanoma
- CNS ca
- germ cell tumours
- neuroendocrine tumours
- blastoma
- mesothelioma
- thyroid cancer
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
TNM staging: what is T?
Tumour
size and extent of the primary tumour
TNM staging: what is N?
Nodes
indicates whether the cancer has spread to nearby lymph nodes (local spread)
TNM staging: what is M?
Metastasis
refers to whether the ca has spread (metastasised) to distant organs or tissues (distant spread)
What would Tx, Nx or Mx mean in TNM staging?
can’t be assessed
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
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
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
Brain and CNS cancers typically affect who?
children and young people
Symptoms of brain and CNS cancers?
new onset seizures, headaches, nausea, drowsiness, visual change, personality change
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
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
Most common intracranial tumours in adults?
brain metastases
What do brain mets signify?
advanced disease state with significant impact on morbidity and mortality
What primary cancers are most likely to metastasise to the brain?
Lung (40-50%)
Breast (15-25%)
Melanoma (5-20%)
Renal (5-10%)
Colorectal
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
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
Diagnosis of brain mets?
GOLD= MRI with contrast for number, size and location
- Biopsy confirms in primary ca site is unknown or imaging inconclusive
Aim of Mx of brain mets?
controlling symptoms, reducing tumour burden and improving QOL
Mx for brain mets?
- supportive care
- radiation therapy
- systemic therapy
- surgical resection
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
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
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
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
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
What drug class in tamoxifen?
selective oestrogen receptor modulator (SERM)= acts as an oestrogen receptor antagonist and partial agonist
Drug used in the Mx of oestrogen receptor positive breast ca?
tamoxifen
Adverse effects of tamoxifen (SERM)?
- vaginal bleeding, amenorrhoea
- hot flushes (3% stop taking due to this)
- VTE
- endometrial ca
What drug class are anastrozole and letrozole?
aromatase inhibitors= reduces peripheral oestrogen synthesis
Drug used in the Mx of ER +ve breast ca in postmenopausal women?
Anastrozole
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
Adverse effects of anastrozole (aromatase inhibitor)?
- osteoporosis (DEXA scan)
- hot flushes
- arthralgia, myalgia
- insomnia
What should be done when initiating pt on aromatase inhibitors for breast ca?
DEXA scan due to risk of osteoporosis
Malignant breast lump is usually what?
painless, but pain can occur
Nipple symptoms of breast ca?
shape in shape, bleeding, tethering, peau d’orange
Diagnosis of breast ca?
mammography and core biopsy
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
Consider a suspected ca referral (2ww) for breast ca in who?
- skin changes that suggest breast ca
- 30yrs+ with unexplained lump in axilla
Non-urgent referral for breast ca in who?
<30yrs with unexplained breast lump with or without pain
Symptoms suggestive of breast ca?
- axillary lump (unexplained)
- breast lump (unexplained)
- nipple changes
- skin changes
- DVT
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
Most common type of breast ca?
invasive ductal carcinoma
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)
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
Surgical options for breast ca: when is mastectomy indicated?
- multifocal tumour
- central tumour
- large lesion in small breast
- DCIS >4cm
- Pt choice
Surgical options for breast ca: when is wide local excision indicated?
- solitary lesion
- peripheral tumour
- small lesion in large breast
- DCIS <4cm
- pt choice
Large breast tumour that is unsutiable for breast conserving surgery?
mastectomy
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
Local recurrence rate of breast ca whatever surgery option was chosen?
5% or less at 5yrs
What index can be used to give indication of survival in breast ca?
Nottingham Prognostic Index
Calculation of Nottingham Prognostic Index?
Tumour Size x 0.2 + Lymph node score +Grade score
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
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%
What does Nottingham Prognostic Index for breast ca not include that can affect survival?
vascular invasion and receptor status
Prior to surgery for breast ca, what determines Mx?
presence or absence of lymphadenopathy
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
Mx of breast ca: women with palpable axillary lymphadenopathy at presentation should have what?
axillary node clearance at primary surgery
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
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
When is adjuvant hormonal therapy offered for breast ca Mx?
if tumours are positive for hormone receptors
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)
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
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
Chemotherapy for breast ca?
Regimen with a taxane and an anthracycline
Side effects of chemo for breast ca (regimen that contains a taxane and an anthracycline)?
neuropathy, neutropenia and hypersensitivity
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
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
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
Chemo Mx for people with ER/PR/HER2 negative (triple negative) invasive breast ca?
neoadjuvant chemo regimen contains a platium and an anthracycline
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
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.
Breast reconstruction options for breast ca?
immediate reconstruction (during mastectomy surgery) or delayed in another operation
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
HRT and breast ca?
- stop HRT
- don’t offer HRT if Hx of breast ca
- consider SSRI to relieve symptoms if not on tamoxifen
What can you consider for premenopausal women with ER +ve invasive breast ca?
ovarian function suppression to reduce risk of recurrence
How long to take tamoxifen or aromatase inhibitor for breast ca?
5yrs
can continue taking to reduce recurrence
Can pt get pregnant on tamoxifen?
not while taking it or within 2m of stopping
Follow up imaging for pt who has been treated for breast ca?
annual mammography for 5yrs or longer until they enter screening programme
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?
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)
BRCA1 and BRCA2 gene increase risk of what?
40% lifetime risk of breast/ovarian ca
What is used for breast screening?
mammography radiography- detects small changes in breast before other S&S of breast ca develop
How often is the breast screening programme?
every 3yrs
When are women offered breast screening?
aged 50-70
should receive 1st invitation within 3yrs of 50th bday
Can women >70yrs get breast screening?
excluded from programme but can get screening by self-referral to local breast screening service
Who may be eligible for breast screening <50yrs?
if have increased risk eg. strong FHx
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
Benefits of breast screening?
- early detection of breast ca
- reduction in mortality
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
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
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
Types of breast cancer?
- invasive ductal carcinoma
- invasive lobular carcinoma
- ductal carcinoma-in situ (DCIS)
- lobular carcinoma-in-situ (LCIS)
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
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)
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
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
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
Inflammatory breast ca?
cancerous cells block lymph drainage resulting in inflamed appearance of breast
rare
Most cases of cervical ca originate from where?
ecto- or endocervical mucosa in the cervical transformation zone
Cervical ca: what usually regressess?
low-grade dysplasia (cervical intraepithelial neoplasia 1- CIN1)
but can progress to high grade dysplasia
When does cervical ca occur?
when high grade dysplastic lesions extend beyond the basement membrane of the cervical epithelium
2 most common types of cervical ca?
squamous cell carcinoma and adenocarcinoma
Main cause of cervical ca?
persistent infection- HPV (human papillomavirus)
How is HPV trsansmitted?
sexual intercourse
What subtype of HPV account for 2/3rds of cervical ca?
16 and 18; 33
HPV detected in 99% cervical ca
Only about 10% of all HPV infections become persistent, which puts women at risk of developing what?
precancerous cervical lesions
Time interval between HPV infection and development of precancerous lesions?
1-10yrs
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
Peak incidence rate of cervical ca?
30-34yrs
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
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)
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
Prevention of cervical ca?
- national cervical screening programme
- national HPV vaccination programme
- consistent use of condoms and practicing safe sex
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)
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.
Cervical ca initial assessment after referral?
punch or excisional biopsy eg. electrosurgical excision and conization of suspicious lesions
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
Common sites of mets from cervical ca?
lungs, liver, bone
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
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
What factors may determine risk of recurrence in cervical ca?
tumour size, margin invl, lymph node invl
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
Mx of cervical ca: Stage IVB (spread to distant organs)?
systemic chemo 1st line
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
What is a radical hysterectomy?
resection of cervix, uterus, parametria and cuff of upper vagina
Most common type of cervical ca?
squamous cell cancer
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
What is an oncogene?
mutated gene that has potential to cause cancer
What. HPV subtypes are non-carcinogenic and associated with genital warts?
6 & 11
Infected endocervical cells (infected with HPV) may undergo changes resulting in the development of what?
Koilocytes
Characteristics of koilocytes?
- enlarged nucleous
- irregular nuclear membrane contour
- nucleus stains darker than normal (hyperchromasia)
- perinuclear halo
What is the Mx of cervical ca determined by?
FIGO staging and wishes of pt to maintain fertility
Stages of the FIGO staging for cervical ca?
IA
IB
II
III
IV
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
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
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
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
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
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
Prognosis of cervical ca?
FIGO stage I= 99% 1yr survival; 96% 5yr
II= 85%; 54%
III= 74%; 38%
IV= 35%; 5%
Cx of cone biopsy or radical trachelectomy eg. in cervical ca?
preterm birth in future pregnancies
Cx of radical hysterectomy?
ureteral fistula
Short term Cx of radiotherapy for cervical ca?
diarrhoea, vaginal bleeding, radiation burns, pain on micturition, tiredness/weakness
Long term Cx of radiotherapy for cervical ca?
ovarian failure, fibrosis of bowel/skin/bladder/vagina, lymphoedema
Cervical ca screening for women aged?
25-64yrs (first invitation issued at 24.5yrs so ensure screening can be done by 25th bday)
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)
Can people 65yrs and older get cervical screening?
invited if recent cervical cytology abnormal
or
if not had screening since 50yrs and request one
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
Cervical ca screening, what if hrHPV detected?
cytology
if this is abnormal then colposcopy
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
Cervical ca screening= hrHPV +ve with cytology abnormal at 12 or 24m?
refer to colposcopy
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
Cervical ca screening= colposcopy normal and adequate?
follow up at 12m screening, if then HPV -ve then return to normal recall
Cervical ca screening= colposcopy inadequate?
repeat screening and colposcopy in 12m; if normal and HPV -ve then return to routine recall
Cervical ca screening: cytology negative means what?
no abnormality detected
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
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
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
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.
What may be done on colposcopy to confirm diagnosis of cervical ca?
biopsy
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)
If pt has been treated for CIN, when should they be followed up for repeat cervical sample?
6m after Tx to test for cure
What is cervical intraepithelial neoplasia (CIN)?
abnormal changes in the transformation zone of cervix
Cervical dysplasia may indicate what?
HIV
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.
Cervical intraepithelial neoplasia (CIN) grade 2 (CIN2)?
two-thirds of the thickness of the surface layer of the cervix is affected.
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.
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.
How often should pt have cervical ca screening if have HIV?
annually and colposcopy at diagnosis
What does dyskaryosis in cervical ca mean?
percancerous changes in cervical cells: can be early indication of cervical ca or HPV infection
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.
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.
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.
What if dyskaryosis is detected on cervical smear?
colposcopy +/- biopsy
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
Why may pt get abdo pain/discomfort/cramping with colorectal ca?
may be due to tumour obstructing bowel or causing inflam
Why may pt with colorectal ca have anaemia?
chronic bleeding from the tumour
Locations of ca in colorectal cancer?
rectal (40%)
sigmoid (30%)
descending colon (5%)
transverse colon (10%)
ascending colon and caecum (15%)
Types of colorectal (colon) ca?
1) sporadic (95%)
2) hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)
3) familial adenomatous polyposis (FAP, <1%)
What may sporadic colon ca be due to?
genetic mutations
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
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
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
Pts with HNPCC are also at higher risk of what?
other ca eg. endometrial ca
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
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%)
What is FAP due to?
mutation in tumour supressor gene called adenomatous polyposis coli gene (APC) located on chromosome 5
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
Pts with FAP are also at risk from what?
duodenal tumours
Variant of FAP?
Gardner’s syndrome- also feature osteomas of skull & mandible, retinal pigmentation, thyroid carcinoma and opidermoid cysts on the skin
What does FAP stand for?
Familial Adenomatous Polyposis
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
Staging system for colorectal ca?
TNM
once staging complete then MDT meeting to formulate Mx plan
Treatment options for colorectal ca?
- surgery
- chemo
- radio
- targeted therapies
Ca of colon is nearly always treated with what?
surgery
Only option for cure in pts with colon ca?
resectional surgery
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
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
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
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)
The operations for colon ca are segmental resections based on what?
blood supply and lymphatic drainage
Type of resection and anastomosis for cancer of the caecal, ascending or proximal transverse colon?
Type of resection= right hemicolectomy
Anastomosis= ileo-colic
Type of resection and anastomosis for cancer of the distal transverse, descending colon?
Type of resection= left hemicolectomy
Anastomosis= colo-colon
Type of resection and anastomosis for cancer of the sigmoid colon?
Type of resection= high anterior resection
Anastomosis= colo-rectal
Type of resection and anastomosis for cancer of the upper rectum?
Type of resection= anterior resection (TME)
Anastomosis= colo-rectal
Type of resection and anastomosis for cancer of the low rectum?
Type of resection= anterior resection (low TME)
Anastomosis= colo-rectal (+/- defunctioning stoma)
Type of resection and anastomosis for cancer of the anal verge?
Type of resection= abdomino-perineal excision of rectum
Anastomosis= none
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)
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.
When is chemotherapy used in colorectal ca?
in neoadjuvant setting (particularly for rectal ca), adjuvant setting and for metastatic disease
Common chemo regimens for colorectal ca?
FOLFOX and FOLFIRI
When is radiation therapy used for colorectal ca?
predominantly for rectal ca in the neoadjuvant or adjuvant setting
Targeted therapies for colorectal ca?
Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), particularly for metastatic disease
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
What is used to guide referral in suspected colorectal ca?
Faecal Immunochemical Test (FIT) instead of doing colonoscopy 1st line
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
What if pt needs FIT test but already had a negative result through the NHS screening programme?
still need another one
What if pt with rectal mass, unexplained anal mass or unexplained anal ulceration?
do not need FIT test, just consider referral for ?colorectal ca
What if FIT test comes back +ve?
refer on suspected ca pathway
What if FIT test negative?
- safety net
- refer on suspected ca pathway if ongoing signif concern (abdo mass)
- still Ix for underlying diagnosis
NHS screening programme for bowel ca offered to who?
every 2yrs to people 50-74yrs (England & Scotland)
Wales: 51-74
NIreland: 60-74hrs
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
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
Abnormal FIT test on NHS screening programme?
offered colonoscopy
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
Possible harms of bowel screening?
anxiety; Cx of colonoscopy (bleeding, bowel perforation); inappropriate reassurance from -ve screening result
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
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
Most colorectal ca develop from what?
adenomatous polyps
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)
Where is endometrial ca classically seen?
post-menopausal women
25% do occur before menopause
Prognosis of endometrial ca?
good due to early detection
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)
Protective factors for endometrial ca?
- multiparity
- COCP
- smoking
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
Postmenopausal bleeding classic symptom of what?
endometrial ca
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
Who should be referred using suspected ca pathway for endometrial ca?
all women >=55yrs who present with postmenopausal bleeding
consider if <55
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
Mx for endometrial ca?
surgery
- localised disease= total abdo hysterectomy with bilateral salpingo-oophorectomy
high-risk disease= postop radiotherapy
Frail elderly women with endometrial ca not suitable for surgery?
progestogen therapy
How is post-menopausal bleeding defined?
unexplained vaginal bleeding more than 12m after menstruation has stopped because of the menopause
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.
Who is typically affected by gastric ca?
older people (1/2 are >75yrs) and male
Most common type of gastric ca?
gastric adenocarcinoma
Where does gastric adenocarcinoma arise from?
glandular epithelium of the stomach lining
RFs for gastric ca?
- Helicobacer pylori
- pernicious anaemic, atrophic gastritis
- diet
- ethnicity: Japan, China
- smoking
- blood group A
Why is H.pylori a RF for gastric ca?
triggers inflam of the mucosa -> atrophy and intestinal metaplasia -> dysplasia
What type of diet increases risk of gastric ca?
salt and salt-preserved foods
nitrates
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
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)
Ix and diagnosis for oesophago-gastric ca?
oesophago-gastro-duodenoscopy with biopsy
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
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
Mx of gastric ca?
surgical options depend on extent and site, include:
- endoscopic mucosal resection
- partial gastrectomy
- total gastrectomy
- chemotherapy
Mx of T1N0 oesophageal ca?
endoscopic mucosal resection for staging
Mx for T1bN0 SCC of the oeophagus?
- definitive chemo or
- surgical resection
pt choice
Surgical Tx of oesophageal ca?
open or minimally invasive oesophagectomy
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
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
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
Mx for SCC of oesophagus (resectable and non-metastatic)?
- radical chemoradio or
- chemoradio before surgical resection
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
1st line palliative chemo for people with HER2-positive metastatic adenocarcinoma of stomach or oesophago-gastric junction?
trastubzumab (in combination with cisplatin and capecitabine)
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.
What can you offer pts with luminal obstruction in oesophageal and oesophageal-gastric junctional ca?
self-expanding stents or radiotherapy
What can you offer pt with outflow obstruction in gastric ca?
uncovered self-expanding metal stents or palliative surgery
What to offer pt immediately after having radical surgery for oesophageal and oesophago-gastric junctional ca?
enteral or parenteral nutrition
Most common malignancy affecting children?
ALL
What does ALL stand for?
Acute lymphoblastic leukaemia
Peak incidence of ALL?
2-5yrs
boys slightly more common
Features of ALL may be divided into what?
those predictable by bone marrow failure eg. anaemia, neutropaenia, thrombocytopenia
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
Why may child get bone pain with ALL?
secondary to bone marrow infiltration
Types of ALL?
- common ALL (75%), CD10 present, pre-B phenotype
- T-cell ALL (20%)
- B-cell ALL (5%)
ALL poor prognostic factors?
- age <2yrs or >10yrs
- WBC >20*10^9/l at diagnosis
- T or B cell surface markers
- non-Caucasian
- male
More common form of acute leukaemia in adults?
acute myeloid leukaemia
AML may occur as what?
primary disease or following a secondary transformation of a myeloproliferative disorder
What does AML stand for?
acute myeloid leukaemia
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
Poor prognostic factors of AML?
> 60yrs
20% blasts after first course of chemo
cytogenetics= deletions of chromosome 5 or 7
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
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
Don’t need to know substypes of AML except what?
Acute promyelocytic leukaemia (APML, the M3 subtype of AML)
What is APML associated with?
the t(15;17) translocation which causes fusion of the PML and RAR-alpha genes
Features of APML?
- presents younger than other types of AML (average=25yrs)
- DIC or thrombocytopenia often
- good prognosis
Mx of APML?
all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemo
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)
Cx of CLL?
- anaemia
- hypogammaglobulinaemia= recurrent infections
- warm autoimmune haemolytic anaemia (in 10-15%)
- transformation to high-grade lymphoma (Richter’s transformation)
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
Ritcher’s transformation is indicated by one the following symptoms….
lymph node swelling
fever without infection
weight loss
night sweats
nausea
abdominal pain
Pt with CLL suddenly becomes very unwell?
Ritcher’s transformation
What does CLL stand for?
chronic lymphocytic leukaemia
What causes CLL?
monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
Most common form of leukaemia seen in adults?
CLL
Features of CLL?
- often asymptomatic= picked up incidental finding of lymphocytosis
- constitutional: anorexia, weight loss
- bleeding, infections
- lymphadenopathy more marked than CML
Ix for CLL?
- Immunophenotyping KEY
- FBC
- Blood film= smudge cells (smear cells)
Immunophenotyping for CLL?
most cases can be identified using panel of antibodies specific for CD5, CD19, CD20, CD23
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)
Smudge cells (smear cells on blood film)?
CLL
Auer rods on myeloperoxidase stain?
AML (APML)
Philadelphia chromosome is present in more than 95% of pts with what?
CML
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.
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%)
Mx of CML?
Imatinib 1st line
- hydroxyurea
- interferon-alpha
- allogenic bone marrow transplant
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
What does CML stand for?
Chronic myeloid leukaemia
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.
When to refer children and young people for immediate specialist assessment for leukaemia if they have what?
unexplained petechiae or hepatosplenomegaly
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.
Way to remember leukaemia ages?
ALL= <5 & >45
CeLLmates= >55, smudge
cells
have
CoMmon= >65, philadelphia chromosome
AMbitions= >75, aurer rods
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)
Refer people using suspected ca referral for lung ca if they…?
- have CXR that suggests lung ca or
- 40yrs+ with unexplained haemoptysis
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
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
Most mesotheliomas are what?
pleural
peritoneal can occur
Features of lung ca?
persistent cough
haemoptysis
dyspnoea
chest pain
weight loss and anorexia
hoarseness
laryngeal nerve
superior vena cava syndrome
When is hoarseness seen in lung ca?
with Pancoast tumours pressing on the recurrent laryngeal nerve
Examination findings of lung ca?
- fixed monophonic wheeze
- clubbing
- supraclavicular lymphadenopathy or persistent cervical lymphadenopathy
What is paraneoplastic syndrome?
rare disorders that occur when immune system has a reaction to ca
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
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
Paraneoplastic features of adenocarcinoma lung ca?
- gynaecomastia
- HPOA
Cx of lung ca?
hoarseness
stridor
What may be noted on bloods for pt with lung ca?
raised platelets
(thrombocytosis)
1st line Ix for lung ca?
CXR
(10% sometimes CXR normal)
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
3 subtypes of non-small cell lung ca?
- Squamous cell carcinoma
- Adenocarcinoma
- Large cell lung carcinoma
Lung ca: squamous cell cancer?
typically central
cavitating lesions are more common than other types
HPOA
What is squamous cell lung ca associated with?
Finger clubbing
and
PTHrP secretion -> hypercalcaemia
Most common type of lung ca in non-smokers?
adenocarcinoma
Lung ca: adenocarcinoma?
- typically peripheral
- most common in lung ca in non-smokers, but majority are still smokers
Lung ca: large cell lung carcinoma?
- typically peripheral
- anaplastic, poorly differentiated tumours with poor prognosis
- may secrete B-HCG
Anaplastic?
term used to describe ca cells that divide rapidly and have little to no resemblance to normal cells
Mx for non-small cell lung ca?
- only 20% suitable for surgery
- curative or palliative radiotherapy
- poor response to chemo
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.
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
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
Lambert-Eaton syndrome in small cell lung ca?
antibodies to voltage gated calcium channels causing myasthenic like syndrome
Small cell lung ca is usually what by the time of diagnosis?
metastatic disease
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
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
Types of lung ca?
Small cell lung ca
Non-small cell lung ca:
- adenocarcinoma
- squamous
- large cell
- alveolar cell carcinoma
- bronchial adenoma
How is lung ca classified?
histologically as SCLC or NSCLC due to different features, Mx and prognosis
What type of lung ca has worse prognosis?
small cell (15%)
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
What type of lung ca most commonly has cavitating lesions?
Squamous (NSCLC)
NSCLC: alveolar cell carcinoma?
not related to smoking
++ sputum
What type of lung ca is mostly carcinoid?
bronchial adenoma (NSCLC)
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
Burkitt’s lymphoma?
high-grade B-cell neoplasm
2 major forms of Birkitt’s lymphoma?
- Endemic (African) form
- Sporadic form
Burkitt’s lymphoma: endemic (African) form?
typically invl. maxilla or mandible
Burkitt’s lymphoma: sporadic form?
abdominal eg ileo-caecal tumours are the most common form; more common in pts with HIV
What is Burkitt’s lymphoma associated with? (gene)
c-myc gene translocation, usually t(8:14)
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
Microscopy findings in Burkitt’s lymphoma?
‘starry sky’ appearance= lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
Mx for Burkitt’s lymphoma?
Rasburicase often given before then chemotherapy
What does chemotherapy used for Burkitt’s lymphoma tend to produce?
a rapid response which may cause tumour lysis syndrome
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)
Cx of tumour lysis syndrome? (5)
hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure
What is tumour lysis syndrome?
potentially life threatening Cx that occurs when ca cells break down rapidly, releasing intracellular contents into blood -> metabolic imbalances
What cancers is TLS most common in?
ones with high cell turnover eg. leukaemia and lymphoma, occasionally highly aggressive solid tumours
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
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.
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.
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.
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.
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.
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
Example of a high grade lymphoma?
Burkitt’s lymphoma
Malignant proliferation of lymphocytes characterised by the presence of Reed-Sternberg cell?
Hodgkin’s lymphoma
Ages most affected by Hodgkin’s lymphoma?
bimodal age distribution: 3rd and 7th decades most common
Histological classification of Hodgkin’s lymphoma?
- Nodular sclerosing (70%)
- Mixed cellularity (20%)
- Lymphocyte predominant (5%)
- Lymphocyte depleted (rare)
What histological type of Hodgkin’s lymphoma has the best prognosis?
Lymphocyte predominant
What histological type of Hodgkin’s lymphoma has the worst prognosis?
Lymphocyte depleted
What histological types of Hodgkin’s lymphoma have a good prognosis?
Mixed cellularity and nodular sclerosing
Lymphocyte predominant= best
What histological type of Hodgkin’s lymphoma is more common in women and associated with lacunar cells?
Nodular sclerosing
What histological type of Hodgkin’s lymphoma is associated with a large number of Reed-Sternberg cells?
Mixed cellularity
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
‘B’ symptoms?
weight loss >10% in last 6m
fever >38ºC
night sweats
RFs for Hodgkin’s lymphoma?
HIV
EBV
Features of Hodgkin’s lymphoma?
- lymphadenopathy (75%)
- systemic B symptoms (25%)
- possible: mediastinal mass- may be symptomatic (cough) or incidental on CXR
Subtypes of ALL?
B-cell ALL (80%)
T-cell ALL (20%)
Causes of ALL?
1) chemoradiation
2) genetic= Down’s (ALL & AML) and translocations
3) infection
How may chemoradiation cause ALL?
cause mutations so increase DNA replication without lymphoblasts actually dying so not differentiating into T and B cells
Translocations that cause ALL?
(12:20)t= children
(9:22)t= adults, Philidelphia chromosome forming BCR-ABL gene
(different Tx for diff translocation)
What virus may cause T-cell ALL?
HTLV
What is associated with good prognosis in ALL?
hyperdiploid blast cells
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
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
What types of leukaemia may result in leukostasis or TLS?
AML or ALL
AML»> for leukostasis
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
What would FBC and blood smear show in ALL?
- decreased RBC and platelets
- variable functional WBC (high or low)
- blood smear= increased immature lymohoblasts
What would bone marrow biopsy show in ALL?
Increased lymphoblasts
>20%
(blast cell predominance)
Immunophenotyping for ALL?
Immunohistochemistry:
- lymphoblasts high
- Tdt +ve
- mpo -ve
Flow cytometry:
- T-ALL= CD2-CD8 (CD3)
- B-ALL= CD10,19,20
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
Why is immunophenotyping and genetic studies done in ALL?
as different Tx for different translocations
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
Systemic chemo agents for ALL?
C.yclophosphamide
V.incristine
A.sparaginase (+/-)
D.oxorubicin
D.examethasone (or pred)
Why is prophylactic intrathecal chemo with methatrexate +/- cranial radiation done in ALL?
risk of meningeal leukaemia in ALL
Advanced therapies for ALL if chemo fails?
- Tyrosine kinase inhibitors eg. imatinib
- Bone marrow transplant if= fail chemo, fail TKIs and poor prognosis
When can tyrosine kinase inhibitors be used for ALL eg. imatinib?
if +ve for (9:22)t and BCR-ABL
Cx and explanation of ALL?
TLS
Malignant cells hit with chemo, burst and release:
- phosphates
- uric acid
- potassium
so cause AKI
Prophylaxis for TLS eg. in ALL?
- IV fluids
- Allopurinol
- Rasburicase
(all 3)
Causes of increased myeloblasts (stopping differentiation into granulocytes)? (eg. AML)
1) chemoradiation
2) Genetic
3) Bone marrow disorder
Genetic causes of increased myeloblasts? (eg. AML)
- Down’s
- AML subtype APL due to (15:17)t with PML-RARA gene
Bone marrow disorders than can cause increased myeloblasts (eg. in AML)?
1) Myelodysplastic syndrome -> progresses to AML
2) CML -> AML
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
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
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
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
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)
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
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)
Bone marrow biopsy in AML?
increased myeloblasts (>20%)
Auer rods
Auer rods?
AML
Immunophenotyping in AML?
Immunohistochemistry:
- mpo +ve (myloperoxodase)
- Tdt -ve
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
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
Clotting screen if DIC in AML?
high PTT
high INR
high d-dimer
low fibrinogen
low RBCs
low platelets
Tx for AML?
- systemic chemo for non-APL subtype
- systemic chemo for APL subtype
- Bone marrow transplant
- Tx of Cx: leukostasis or TLS
Systemic chemo for AML (non-APL subtype)?
agents= Cytarabine and daunorubicin
induction -> consolidation -> maintenance
goal= complete remission
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
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
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)
Tx of leukostasis in AML?
1) cytoreduction= leukapheresis (take away myeloblasts blocking vessels) and hydroxyurea (reduce no. of myeloblasts)
2) then chemo
Prevention/Tx of TLS in AML?
- allopurinol +
- rasburicase +
- IV fluids
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
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
Subtype of AML?
APL (Acute promyelocytic leukemia)
alcohol-induced lymph node pain?
Hodgkin’s lymphoma
Lymphadenopathy in Hodgkin’s lymphoma?
- common in neck (cericval/supraclavicular) > axillary > inguinal
- usually painless, non-tender, asymmetrical
- alcohol induced LN pain (<10% pts)
B symptoms in Hodgkin’s lymphoma?
weight loss
pruritus
night sweats
fever (Pel-Ebstein)
Ix for Hodgkin’s lymphoma?
- normocytic anaemia
- esosinophilia
- LDH raised
- Lymph node biopsy= Reed-Sternberg cells diagnostic
Normocytic anaemia in Hodgkin’s lymphoma?
may be multifactorial eg. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia
What causes eosinophilia in Hodgkin’s lymphoma?
production of cytokines eg. IL-5
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)
Reed-Sternberg cells seen in what?
Hodgkin’s lymphoma
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)
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
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.
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)
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
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
What is combined modality therapy (CMT)?
chemotherapy followed by radiotherapy
2 combinations of chemotherapy that can be used for Hodgkin’s lymphoma?
ABVD= standard
BEACOPP= alternative with better remission rates but higher toxicity
ABVD chemo regimen for Hodgkin’s lymphoma?
doxorubicin
bleomycin
vinblastine
decarbazine
BEACOPP chemo regimen for Hodgkin’s lymphoma?
bleomycin
etoposide
doxorubicin
cyclophosphamide
vincristine
procarbazine
prednisone
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
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
Lymphoma definition?
malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs
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
Non-hodgkin’s lymphoma may affect what cells?
B or T cells
further classified as high or low grade
What is more common: NHL or HL?
NHL
What age is usually affected by non-hodgkin’s lymphoma?
typically elderly, >75yrs
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)
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)
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
Signs of Non-Hodgkin’s lymphoma?
- weight loss
- lymohadenopathy (cervical, axillary, inguinal)
- palpable abdo mass: hepatomegaly, splenomegaly, lymph nodes
- testicular mass
- fever
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
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
Classification to stage NHL?
Lugano staging
Mx of NHL depends on what?
the sub-type
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
Example chemo regimen for NHL?
CHOP:
cyclophosphamide
doxorubicin (hydroxydaunorubicin)
vincristine (Oncovin®)
prednisolone
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
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
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
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
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
Type of referrals for NHL or HL?
- adult= suspected ca pathway referral (within 2w)
- children/young adult= very urgent (within 48hrs)
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
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.
Most aggressive form of malignant melanoma?
nodular
other forms spread more slowly
Subtypes of melanoma?
1) Nodular
2) Superficial spreading
3) Lentigo maligna
4) Acral lentiginous
Melanoma: superfical spreading type?
70% of cases
Typically= arms, legs, back & chest, young people
Appearance= growing mole with diagnostic features
Melanoma: nodular type?
second commonest
Sun-exposed skin, middle aged
Red or black lump or lump which bleeds or oozes
Melanoma: lentigo maligna type?
less common
chronically sun exposed skin, older people
a growing mole with diagnostic features
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
Rare forms of melanoma?
desmoplastic melanoma, amelanotic melanoma, or melanoma arising in other parts of the body such as ocular melanoma.
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
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
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
Most important factor in determining prognosis of pts with malignant melanoma?
the invasion depth of a tumour (Breslow depth)
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%
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.
Most common tumour causing bone mets? (in descending order)
prostate
breast
lung
Most common sites for bone mets (in descending order)?
spine
pelvis
ribs
skull
long bones
Features of bone mets?
bone pain
pathological fractures
hypercalcaemia
raised ALP
Lung mets are seen with what cancers?
breast
colorectal
renal cell
bladder
prostate
Cannonball mets?
multiple round well-defined lung secondaries most commonly seen with renal cell ca, may also occur 2 to choriocarcinoma and prostate ca
Clacification in lung mets?
uncommon except in chondrosarcoma or osteosarcoma
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)
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)
Example of non-epthelial malignancies? (can be treated regardless of primary site)
lymphoma
other haem malignancies
melanoma
sarcoma
germ-cell tumours
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
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
Presentations of MUO with poor prognosis?
multiple mets incl. brain involvement- do not offer chemo unless clinical trial
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.
How are metastatic bone tumours described?
blastic
lytic
or mixed
What metastatic bone tumours have the lowest risk of spontaneous fractures?
osteoblastic metastatic disease lower risk compared to oestolytic lesions of similar size
What metastatic bone lesions are most prone to spontaneous fracture?
lesions affecting peritrochanteric region because of the loading forces at that site
Scoring system to stratify the risk of spontaneous fracture for bone mets of varying types?
Mirel Scoring system
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
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
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
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
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
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)
Another name for myeloma?
multiple myeloma (same thing)
Multiple myeloma?
progressive malignant disease characterised by proliferation of abnormal plasma cells in bone marrow and abnormal monoclonal immunoglobulins in the blood
What organs/systems does multiple myeloma afffect?
bones
kidneys
blood
immune system
Multiple myeloma more common in what gender/age?
men
increases with age
Prognosis of multiple myeloma?
usually incurable but can disease control can be achieved for several yrs
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
Cx of multiple myeloma?
- Pathological bone fractures.
- Spinal cord compression.
- Renal damage.
- Hypercalcaemia.
- Impaired resistance to infection.
- Anaemia.
- Bleeding disorders.
- Hyperviscosity of the blood.
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
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
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
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)
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)
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).
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
What to do if serum and/or urine protein electrophoresis suggest myeloma?
urgent referral to haematologist within 2w for further Ix to confirm
Tx for multiple myeloma depends on what?
age
disease stage
prognosis
cormorbidities
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
Symptoms of hypercalcaemia eg. in myeloma?
bone pain, abdominal pain, depression, confusion, muscle weakness, constipation, thirst, and polyuria
Multiple myeloma may present with what?
pathological fractures and recurrent infection
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.
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
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)
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.
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.
Plasma cell leukaemia (differential for myeloma)?
Clinical features include bone pain, fatigue, recurrent infection, mucosal bleeding, hypercalcaemia, renal impairment, hepatomegaly, and splenomegaly.
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.
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.
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
What may peripheral blood film show in multiple myeloma?
rouleaux (aggregations of red blood cells), which might suggest underlying paraproteinaemia.
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.
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.
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
What should be avoided in pts with myeloma?
aminoglycosides due to risk of renal toxicity
Chemotherapeutic drugs for myeloma?
cyclosphoshamide, doxirubicin, carfilozmib, bortezombin or melphalan
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.
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
Myeloma arises due to what?
genetic mutations that occur as B-lymphocytes differentiate into mature plasma cells
Median age at presentation of myeloma?
70yrs
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
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
What can constipation, nausea, anorexia and confusion in myeloma be caused by?
hypercalcaemia
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
Why do you get anaemia in myeloma?
bone marrow crowding suppresses erythropoiesis leading to anaemia
fatigue and pallor
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
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
Why may pts with myeloma have increased susceptibility to infection?
a reduction in normal production of immunoglobulins
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)
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.
What type of malignancy is a chronic relapsing and remitting and deemed incurable?
myeloma
Aims of Mx for myeloma?
control symptoms, reduce Cx and prolong survival
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.
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.
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.
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
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.
How many ca pts are affected by spinal cord compression?
up to 5%
Neoplastic spinal cord compression- most common type?
extradural compression- usually due to vertebral body mets
Neoplastic spinal cord compression is more common in pts with what ca?
lung, breast and prostate
Earliest and most common symptom of neoplastic spinal cord compression?
back pain
may be worse lying down and coughing
Features of neoplastic spinal cord compression?
- back pain
- lower limb weakness
- sensory loss and numbness
- neuro signs depend on level of lesion
Neoplastic spinal cord compression: lesions above L1 usually result in what?
UMN signs in legs and a sensory level
Neoplastic spinal cord compression: lesions below L1 usually result in what?
LMN signs in legs and perianal numbness
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
Ix for neoplastic spinal cord compression?
urgent (within 24hrs of presentation) whole MRI spine
Mx for neoplastic spinal cord compression?
high dose oral dexamethasone
urgent oncology assessment to consider radiotherapy or surgery
Most common type of oesophageal ca?
adenocarcinoma
What pts are more likely to develop adenocarcinoma of the oesophagus?
those with Hx of GORD or Barrett’s
Oesophageal ca: adenocarinoma vs squamous cell cancer epidemiology?
A= most common type in UK/US
SCC= most common type in developing world
Oesophageal ca: adenocarinoma vs squamous cell cancer location?
A= lower third, near the gastroesophageal junction
SCC= upper 2/3rds of oesophagus
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
Features of oesophageal ca?
- dysphagia (most common): progressive
- anorexia and weight loss
- vomiting
- odynophagia, hoarseness, malaena, cough
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
Mx for operable disease (T1N0M0) in oesophageal ca?
surgical resection- most common procedure is Ivor-Lewis type oesophagectomy
Mx for oesophageal ca?
surgical resection if possible
may need adjuvant chemo
Biggest challenge in surgical resection for oesophageal ca?
anastomotic leak, with an intrathoracic anastomosis resulting in mediastinitis
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
Most common ovarian ca?
Serous epithelial ca
Secondary mets can occur in ovary, most commonly from where?
ca of endometrium, breast and GI tract
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)
Lifetime risk of women being diagnosed with ovarian ca?
1 in 50
What reduces risk of ovarian ca?
- high no. of pregnancies
- breastfeeding
- COCP
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)
What to do if suspect ovarian ca?
- exam abdo and pelvis
- if normal then CA125
Suspect ovarian ca and exam of abdo and pelvis= ascites or pelvic/abdo mass that is not caused by uterine fibroids?
urgent referral
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
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
Peak age for ovarian ca?
60yrs
Why does ovarian ca have poor prognosis?
due to late diagnosis
Where is often the site of origin of many ‘ovarain ca’?
distal end of fallopian tube
RFs for ovarian ca?
- FHx= mutations of BRCA1 or BRCA2 gene
- many ovulations= early menarche, late menopause, nulliparity
eg. when have ‘more’ ovulations
What cancers have notoriously vague symptoms/non specific presentation so often diagnosed late?
ovarian
Abdo distension and bloating, abdo and pelvic pain, urinary symptoms eg. urgency, early satiety and diarrhoea?
?ovarian ca
What is classed as a raised CA125?
35 IU/mL or greater
What may increase CA125?
ovarian ca
endometriosis
menstruation
benign ovarian cysts
other conditions
Can CA125 be used for screening for ovarian ca in asymptomatic women?
NO
not very specific
Diagnosis for ovarian ca?
difficult, usually involves diagnostic laparotomy
Mx for ovarian ca?
usually combination of surgery and platinum-based chemo
Prognosis of ovarian ca?
- 80% have advanced disease at presentation
- 5yr survival is <35%
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
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
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
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
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)
Over 80% of pancreatic tumours are what?
adenocarcinoma
Where do adenocarcinomas of the pancreas typically occur?
head of the pancreas
Is pancreatic ca often diagnosed early or late?
late as non-specific
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
Painless jaundice
pancreatic ca
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)
What picture do LFTs show in pancreatic ca?
cholestatic LFTs
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
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
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.
Ix for pancreatic ca?
- high-resolution CT scanning Ix of choice
- can do USS
‘double duct’ sign on imaging
‘Double duct’ sign on imaging?
pancreatic ca
presence of simultaneous dilation of the common bile and pancreatic ducts
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
Side-effects of a Whipple’s resection for pancreatic ca?
dumping syndrome and peptic ulcer disease
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
Common chemo drugs for pancreatic ca?
1 or more than 1 of:
gemcitabine
capecitabine
fluorouracil (5FU)
irinotecan
oxaliplatin
nab-paclitaxel (Abraxane)
cisplatin
A pathological fracture occurs in…
abnormal bone due to insignificant injury
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
Metastatic tumours that may cause pathological fractures?
breast
lung
thyroid
renal
prostate
Primary malignant tumours that may cause pathological fractures?
chondrosarcoma
osteosarcoma
Ewing’s tumour
Red flags for breast ca?
lump, changes to skin or nipple, change in shape, discharge
Red flags for lung ca?
persitent cough, haemoptysis, chest pain, SOB, non-resolving LRTI
Red flags fro prostate ca?
nocturia, hesitancy, incomplete bladder emptying
Red flags for bowel ca?
PR bleeding, change in bowel habit, abdo pain, tenesmus
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)
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
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
Non surgical oncology: what does curative/radical mean?
aim to cure
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
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.
Non surgical oncology: what goes palliative/disease control mean?
not curative, but aimed at improving quality of life and survival
Examples of systemic anti-cancer therapy?
- cytotoxic therapy
- targeted therapy
- endocrine therapy
- immunotherapy
- bisphosphonates
What does chemotherapy do?
multiple classes of agents
all affect cell cycle in some way
cytotoxic agents- cause cell death
Examples of endocrine Tx?
Tamoxifen and aromatase inhibitors for breast ca
Prostate= GNRH analogues eg. zoladex
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
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)
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
Principle of radiotherapy?
Use maximum dose for tumour control
Whilst minimising dose to normal surrounding tissue
Radiotherapy techniques?
- IMRT
- SABR
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
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
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
General side effects of immunotherapy?
can be multisystem inflammation, including endocrine disturbance. Usually treated with high dose steroids – SPEAK TO AOS team early
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)
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
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
Mx for chemo side effects: constipation? (preventative/Mx)
Esp. if on 5HT3 antagonists (ondansetron)
Laxatives, enema
Consider bowel obstruction
Mx for chemo side effects: stomatitis/mucositis? (preventative/Mx)
Difflam, Bioxtra gel, analgesia
Mucositis
Mx for chemo side effects: other? (preventative/Mx)
5FU/Capecitabine can causes coronary spasm-chest pain/ bradycardias
See UKONS for Ix and management.
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)
Immunotherapy toxicity?
Hepatitis
Nephritis
Colitis
Pneumonitis
MYOCARDITIS
Skin, joints
Hypophysitis…. But can affect any organ
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
Examples of oncology emergencies?
- Metastatic Spinal Cord Compression (MSCC)
- Hypercalcaemia
- SVC Obstruction
- Seizure
- Venous or Arterial
- Thromboembolism
- Pleural Effusion
- Bowel Obstruction
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
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
Mx of neutropenic sepsis?
ABCDE
Must be given the first dose of IV Abx withinone hourof 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
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.
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.
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
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 ↓
Diagnosis for spinal cord compression?
MRI WHOLE SPINE
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
What electrolyte abnormality is common in advanced ca?
hypercalcaemia
Example of why you get hypercalcaemia in advanced ca?
bone mets
production of ectopic PTHrp (parathyroid hormone related peptide) by ca- esp SCC
Mx of hypercalcaemia in ca?
rehydrate- manage AKI
IV bisphosphonates (zolendronate, pamidronate)
manage the cause if possible- treat the ca
Symptoms of hypercalcaemia in ca?
bones, moans, stones, abdo groans
Hypercalcaemia in ca is often associated with what?
AKI
What does the SVC provide?
the venous drainage for the head, neck, upper limbs and the upper thorax
What happens when SVC is obstructed?
collateral pathways form to provide an alternative route for blood to return to the right atrium
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
Symptoms of SVCO?
- dyspnoea
- chest pain, often at rest
- cough
- neck and face swelling
- arm swelling
- others= dizziness, headache, visual disturbance, nasal stuffiness, syncope
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
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
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
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
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
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
In ca pts with N/V what antiemetics should you not prescribe together?
metoclopramide and cylixine DO NOT prescribe together
What antiemetics can be used in ca pts with N/V in difficult cases?
haloperidol, olanzapine, levomepromazine
What antiemetic is contraindicated in epilepsy?
metoclopramide
What might cause seizures in ca pts?
brain mets
primary CNS ca
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
Electrolyte disturbances in ca pts may be secondary to what?
ca or Tx
Causes of hyponatraemic in ca pts?
tumour, recent steroids
Causes of hypercalcaemia in ca pts?
bone mets, SCC lung
Causes of hypocalcaemia in ca pts?
chemo, bisphosphonates, refeeding
Causes of hyperkalaemia in ca pts?
renal failure, tumour lysis syndrome
Causes of hypokalaemia in ca pts?
chemo, refeeding, diarrhoea
Causes of hypomagnasaemia in ca pts?
chemo, refeeding, EGFR inhibitor
Mx for replacement strategies for electrolyte disturbances in ca pts?
clinical guidelines
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
Some ca pts can’t have what medication?
DOACs= GI infiltration, rectal tumours that are bleeding, varices
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
Any oncology emergency?
ask acute oncology team for advice
Prostate ca?
malignant tumour of prostate
Most cancers of the prostate (95%) are what?
adenocarcinomas
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
Most prostate ca are slow or fast growing?
indolest and grow slowly- minority are aggressive and invade local structures or metastasise to remote tissues
Localised prostate ca usually develops where?
in outer zone of prostate where it rarely causes symptoms
Locally advanced prostate ca?
extends beyond the capsule of prostate and is often asymptomatic when diagnosed
Metastatic prostate ca mostly affects where?
bones- causes pain and fragility fractures
RFs for prostate ca?
age
black ethnicity
FHx
Symptoms of prostate ca?
unexplained…
- lower back or bone pain
- lethargy
- erectile dysfunction
- haematuria
- anorexia/weight loss
Assessment of pt with suspected prostate ca?
- digital rectal exam (DRE)
- prostate-specific antigen (PSA) test
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)
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
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
What does LHRH agonists stand for eg. goserelin?
luteninizing horomone releasing hormone agonists
Examples of chemo regimens for prostate ca?
- docetaxel + prednisolone
- cabazitaxel + pred (2nd line)
- 3rd line: dexamethasone
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
Mx for sexual dysfunction in pt with prostate ca?
phosphodiesterase-5 (PDE-5) inhibitor eg. sildenafil
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
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.
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.
Candidates for active surveillance in prostate ca Mx should…
have had at least 10 biopsy cores taken
have at least one re-biopsy.
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
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
1st line Ix for suspected clinically localised prostate ca?
multiparametric MRI: results reported using a 5-point Likert scale
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.
Cx of radical prostatectomy?
erectile dysfunction
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
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
Bicalutamide for prostate ca Mx?
non-steroidal anti-androgen
blocks the androgen receptor
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
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
Bilateral orchidectomy for prostate ca?
used to rapidly reduce testosterone levels
What is PSA?
serine protease enzyme produced by normal and malignant prostate epithelial cells
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
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
What % of prostate ca will have normal PSA?
15%
Suspected testicular ca on clinical exam (or incidentially following USS of scrotum)?
urgent urology referral (using suspected ca pathway)
Consider arranging bloods for what at the time of referral for suspected testicular ca?
tumour markers= AFP, hCG, LDH
Most common malignancy in men 20-30yrs?
testicular
95% of testicular ca are what type of tumour?
germ-cell tumours
Types of germ cell tumours?
seminomas
non-seminomas: including embryonal, yolk sac, teratoma and choriocarcinoma
Types of non-germ cell tumours?
Leydig cell tumours
Sarcomas
Peak incidence for teratoma and seminomas?
T= 25yrs
S= 35yrs
RFs for testicular ca?
- infertility (x3 increase risk)
- cryptorchidism
- FHx
- Klinefelter’s syndrome
- mumps orchitis
Features of testicular ca?
- painless lump (most common)
- pain (minority)
- hydrocele
- gynaecomastia
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
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
Diagnosis of testicular ca?
USS
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
Prognosis of testicular ca?
generally excellent
Seminomas= 5yrs survival 95% if stage I
Teratomas= 85% if stage I
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)
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.
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
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
Head and neck ca?
umbrella term, typically includes:
- oral cavity ca
- ca of the pharynx (incl oropharynx, hypopharynx, nasopharynx)
- ca of the larynx
Features of head and neck ca?
neck lump
hoarseness
persistent sore throat
persistent mouth ulcer
Consider suspected ca pathway referral for laryngeal ca in people…
aged 45yrs+ with:
- persistent unexplained hoarseness or
- unexplained lump in neck
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
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
Consider suspected ca referral for thryoid ca in people with…
unexplained thyroid lump
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
Pathology of non seminomatous germ cell tumours?
heterogenous texture with occasional ectopic tissue such as hair
Pathology of seminomas?
Sheet like lobular patterns of cells with substantial fibrous component. Fibrous septa contain lymphocytic inclusions and granulomas may be seen.
Types of non seminomatous germ cell tumours?
Teratoma
Yolk sac tumour
Choriocarcinoma
Mixed germ cell tumours (10%)
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%
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
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)
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
Cell type in seminomas vs non-seminomas (NSGCTs)?
S= germ cells that are undifferentiated
N-S= germ cells that are differentiated into various tissues
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
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
RFs for developing N&V side effects of chemo?
- anxiety
- <50yrs
- concurrent use of opioids
- type of chemo used
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
Cyclophosphamide?
alkylating agent used in the management of cancer and autoimmune conditions. It works by causing cross-linking of DNA
Adverse effects of cyclophosphamide?
haemorrhagic cystitis: incidence reduced by the use of hydration and mesna
myelosuppression
transitional cell carcinoma
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
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)
Cytotoxic agents: alkylating agents= cyclophosphamide MOA and adverse effects?
Alkylating agent - causes cross-linking in DNA
Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma
Cytotoxic agents: cytotoxic antibodies= bleomycin MOA and adverse effects?
Degrades preformed DNA
Lung fibrosis
Cytotoxic agents: cytotoxic antibodies= anthracyclines (eg. doxorubicin) MOA and adverse effects?
Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis
Cardiomyopathy
Cytotoxic agents: antimetabolites= methotrexate MOA and adverse effects?
Inhibits dihydrofolate reductase and thymidylate synthesis
Myelosuppression, mucositis, liver fibrosis, lung fibrosis
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
Cytotoxic agents: antimetabolites= 6-mercaptopurine MOA and adverse effects?
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
Myelosuppression
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
Cytotoxic agents: acts on microtubules= vincristine, vinblastine MOA and adverse effects?
Inhibits formation of microtubules
Vincristine: Peripheral neuropathy (reversible) , paralytic ileus
Vinblastine: myelosuppression
Cytotoxic agents: acts on microtubules= docetaxel MOA and adverse effects?
Prevents microtubule depolymerisation & disassembly, decreasing free tubulin
Neutropaenia
Cytotoxic agents: topoisomerase inhibitors= irinotecan MOA and adverse effects?
Inhibits topoisomerase I which prevents relaxation of supercoiled DNA
Myelosuppression
Cytotoxic agents: other= cisplatin MOA and adverse effects?
Causes cross-linking in DNA
Ototoxicity, peripheral neuropathy, hypomagnesaemia
Cytotoxic agents: other= hydroxyurea (hydroxycarbamide) MOA and adverse effects?
Inhibits ribonucleotide reductase, decreasing DNA synthesis
Myelosuppression
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
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
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
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.
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
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
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)
What tumour markers are monoclonal antibodies?
CA 125
CA 19-9
CA 15-3
What tumour markers are tumour antigens?
PSA
AFP
CEA
S-100
Bombesin
Tumour markers: CA 125 association?
ovarain ca
endometriosis, PID, menstruation, pregnancy
Tumour markers: CA 19-9 association?
pancreatic ca, gallbladder ca
gallstones, pancreatitis, liver disease
Tumour markers: CA 15-3 association?
breast ca
benign breast conditions, liver disease
Tumour markers: prostate specific antigen (PSA) association?
prostate ca
BPH, prostatitis
Tumour markers: Alpha-feto protein (AFP) association?
hepatocellular carcinoma, testicular ca, teratoma
pregnancy, liver cirrhosis, hepatitis
Tumour markers: Carcinoembryonic antigen (CEA) association?
colorectal ca
also breast, lung, pancreatic ca
smoking, IBD, liver disease
Tumour markers: S-100 association?
melanoma
schwannomas
Tumour markers: bombesin association?
small cell lung carcinoma
gastric ca
neuroblastoma
Tumour markers: hCG?
testicular ca, choriocarcinoma
pregnancy
Tumour markers: lactate dehydrogenase (LDH)?
lymphoma, leukaemia, testical ca
general tissue damage, HF, anaemia, infections
Tumour markers: thyroglobulin?
thyroid ca
thyroiditis, goiter
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
Most common cause for hepatocellular carcinoma (HCC)
chronic hep B worldwide
chronic hep c in europe
Main RF for developing HCC?
liver cirrhosis, eg. secondary to hep B & C, alcohol, haemochromatosis and primary biliary cirrhosis
Wilson’s is the exception
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
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
What should be considered for high risk groups for HCC?
screening with USS (+/- alpha-fetoprotein)
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
Mx options for HCC?
early disease: surgical resection
liver transplantation
radiofrequency ablation
transarterial chemoembolisation
sorafenib: a multikinase inhibitor
Do pts with thyroid ca get features of hyper or hypothyroidism?
not commonly as they rarely secrete thyroid hormones
Type of thyroid ca?
- papillary (70%)
- follicular (20%)
- medullary (5%)
- anaplastic (1%)
- lymohoma (rare)
What type of thyroid ca has an excellent prognosis and is often in young females?
papillary
What is medullary thyroid ca?
ca of parafollicular (C) cells, secrete calcitonin, part of MEN-2
What type of thyroid ca is not responsive to treatment and can cause pressure symptoms?
anaplastic
What type of thyroid ca is associated with Hasimoto’s thyroiditis?
lymphoma thyroid ca
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
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
Thyroid ca: follicular adenoma?
Usually present as a solitary thyroid nodule
Malignancy can only be excluded on formal histological assessment
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
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.
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.
Penile ca?
rare malignancy that affects the penis
How does penile ca typically present?
painless lesion or ulcer on glans or foreskin
may get discharge or bleeding
RFs for penile ca?
phimosis
poor hygiene
smoking
HPV infection
Diagnosis of penile ca?
biopsy and histopathological exam of lesion
Mx of penile ca?
depends on stage
surgery, radio, chemo or combination
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.
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
Follow up for pt with prostate ca being managed with watchful waiting?
- PSA at least once per yr
-DRE not recommended on routine basis
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.
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
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.
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.
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.
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
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
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
Bone sarcomas?
osteosarcoma
chondrosarcoma
Ewing’s sarcoma
Soft tissue sarcomas?
Liposarcoma
Rhabdomyosarcoma (striated muscle origin)
Synovial sarcoma
Fibrosarcoma
Angiosarcoma
Leiomyosarcoma (smooth muscle origin))
Presentations of sarcoma?
- pain
- swelling or palpable mass (soft tissue>bone)
- impaired function
- pathologic fractures (bone)
- systemic symptoms
Ix for sarcoma?
X-ray, CT, MRI, PET
biopsy= fine needle aspiration, core needle biopsy or incisional biopsy for histopath
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)
