The Medical & Surgical Handbook

The MedSurg Handbook
Notes on medicine and surgery
Written by Garry KJ Pettet

..................................................................................ANAESTHETICS 8
ACUTE PAIN AND THE ANAESTHETIST ..............................................................9
INTERMITTENT POSITIVE PRESSURE VENTILATION .....................................(IPPV) 13
PREOPERATIVE GRADING ...........................................................................16
LOCAL AND REGIONAL ANAESTHESIA .............................................................17
............................................................................BREAST SURGERY 19
BENIGN BREAST PAIN ..............................................................................20
BREAST LUMPINESS AND LUMPS ...................................................................22
CYSTS ................................................................................................23
DUCT PAPILLOMA ...................................................................................24
FIBROADENOMA .....................................................................................25
FIBROADENOSIS ....................................................................................26
INFECTION OF THE BREAST ........................................................................28
MAMMARY DUCT ECTASIA ..........................................................................30
NIPPLE DISCHARGE .................................................................................31
TRAUMA TO THE BREAST ...........................................................................32
..........................................................................CANCER MEDICINE 33
ACUTE LYMPHOBLASTIC LEUKAEMIA ......................................................(ALL) 36
ACUTE MYELOGENOUS LEUKAEMIA .......................................................(AML) 37
ACUTE PROMYELOCYTIC LEUKAEMIA ....................................................(APML) 39
BREAST CANCER ....................................................................................40
CANCER GENETICS ..................................................................................48
PALLIATIVE CARE IN CANCER PATIENTS ..........................................................50
CARCINOMA OF THE BRONCHUS ...................................................................52
CARCINOMA OF THE PROSTATE ....................................................................57
CHEMOTHERAPY .....................................................................................60
CHRONIC LYMPHOCYTIC LEUKAEMIA ......................................................(CLL) 62
CHRONIC MYELOID LEUKAEMIA ...........................................................(CML) 64
HAIRY CELL LEUKAEMIA ....................................................................(HCL) 66
HODGKIN’S DISEASE ........................................................................(HD) 67
MYELOABLATIVE THERAPY WITH HAEMOPOIETIC PROGENITOR CELL SUPPORT .....(HPCS) 69
MYELOMA ............................................................................................72
NON-HODGKIN’S LYMPHOMA .............................................................(NHL) 75
PAIN CONTROL IN CANCER PATIENTS .............................................................77
STAGING OF CANCER ...............................................................................80
...................................................................................CARDIOLOGY 82
ANGINA PECTORIS ..................................................................................83
AORTIC REGURGITATION ....................................................................(AR) 87
AORTIC STENOSIS ...........................................................................(AS) 89
ATRIAL TACHYCARDIAS .............................................................................91
Copyright Garry KJ Pettet 2005 - 2009
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BUNDLE BRANCH BLOCK ...........................................................................93
CARDIOGENIC SHOCK (ACUTE HEART FAILURE .................................................) 94
CHRONIC HEART FAILURE ..........................................................................96
INFECTIVE ENDOCARDITIS .................................................................(IE) 101
MITRAL REGURGITATION ..................................................................(MR) 104
MITRAL STENOSIS .........................................................................(MS) 106
MYOCARDIAL INFARCTION .................................................................(MI) 108
PULMONARY OEDEMA .............................................................................113
UNSTABLE ANGINA ................................................................................115
VENTRICULAR TACHYARRHYTHMIAS .............................................................116
WOLFF-PARKINSON-WHITE (WPW) SYNDROME .............................................119
...............................................................................DERMATOLOGY 120
BULLOUS DISEASE ................................................................................121
ECZEMA (A.K.A. DERMATITIS ...................................................................) 124
DERMATOLOGY TERMINOLOGY ...................................................................129
LICHEN PLANUS ...................................................................................130
MALIGNANT CUTANEOUS TUMOURS .............................................................131
PITYRIASIS ROSEA ................................................................................134
POTENTIALLY PRE-MALIGNANT CUTANEOUS TUMOURS ........................................135
PSORIASIS .........................................................................................137
WHEN SKIN STRUCTURE OR FUNCTION FAILS ..................................................140
..........................................................................ENDOCRINOLOGY 143
ACROMEGALY ......................................................................................144
ADDISON’S DISEASE ..............................................................................146
CUSHING’S SYNDROME ...........................................................................149
DIABETES ..........................................................................................153
NON-KETOTIC HYPEROSMOLAR STATE ..........................................................173
GOITRE ............................................................................................174
GOUT AND HYPERURICAEMIA ....................................................................177
HYPERCALCAEMIA .................................................................................180
HYPERPROLACTINAEMIA ..........................................................................184
HYPERTHYROIDISM ...............................................................................186
HYPOCALCAEMIA ..................................................................................192
HYPOPITUITARISM ................................................................................194
HYPOTHYROIDISM ................................................................................196
MYXOEDEMA COMA ...............................................................................199
OSTEOPOROSIS ...................................................................................200
PAGET’S DISEASE .................................................................................204
PITUITARY SPACE-OCCUPYING LESIONS AND TUMOURS ......................................206
REGULATION OF CALCIUM METABOLISM ........................................................208
....................................................................GASTROENTEROLOGY 210
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ACUTE GASTRITIS .................................................................................211
ACUTE HEPATITIS .................................................................................212
ACUTE HEPATITIS B VIRUS ..............................................................(HBV) 213
ACUTE HEPATITIS C VIRUS ..............................................................(HCV) 215
ACUTE HEPATITIS D VIRUS (HDV OR DELTA VIRUS .........................................) 216
ACUTE PANCREATITIS .............................................................................217
ASCITES ............................................................................................220
AUTOIMMUNE HEPATITIS .........................................................................222
BACTERIAL OVERGROWTH ........................................................................224
CHOLESTATIC JAUNDICE .........................................................................225
CHRONIC GASTRITIS ..............................................................................226
CHRONIC HEPATITIS ..............................................................................227
CHRONIC HEPATITIS B INFECTION ..............................................................229
CHRONIC HEPATITIS C INFECTION ..............................................................231
CHRONIC HEPATITIS D INFECTION ..............................................................232
CHRONIC PANCREATITIS .........................................................................233
CIRRHOSIS ........................................................................................235
COELIAC DISEASE .................................................................................238
CONJUGATED CONGENITAL HYPERBILIRUBINAEMIAS ..........................................240
CONSTIPATION ....................................................................................241
DERMATITIS HERPETIFORMIS ....................................................................243
DIARRHOEA .......................................................................................244
DYSPHAGIA ........................................................................................247
FULMINANT HEPATIC FAILURE ...........................................................(FHF) 248
GASTRO-OESOPHAGEAL REFLUX DISEASE ......................................................250
HEPATITIS A VIRUS ......................................................................(HAV) 253
INTESTINAL RESECTION ..........................................................................255
JAUNDICE ..........................................................................................257
MALABSORPTION ..................................................................................261
MALIGNANT LIVER TUMOURS ....................................................................262
PEPTIC ULCER DISEASE ...........................................................................264
PORTAL HYPERTENSION ..........................................................................267
RADIATION ENTERITIS ............................................................................269
TROPICAL SPRUE ..................................................................................270
VOMITING ..........................................................................................271
WHIPPLE’S DISEASE ..............................................................................273
......................................................................GENERAL MEDICINE 274
ACUTE LUMBAR DISC PROLAPSE .................................................................275
ACUTE RENAL FAILURE ...................................................................(ARF) 276
ALCOHOL ABUSE ..................................................................................281
ANAEMIA OF CHRONIC DISEASE .................................................................285
ANXIETY DISORDER ...............................................................................286
CAUSES OF SPINAL PAIN .........................................................................289
CEREBRAL INFARCTION ...........................................................................290
CEREBROVASCULAR DISEASE AND STROKE ....................................................295
CHRONIC RENAL FAILURE ................................................................(CRF) 297
CLUSTER HEADACHE ..............................................................................303
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DELIRIUM ..........................................................................................304
DEMENTIA .........................................................................................306
DEPRESSION ......................................................................................309
FOLATE DEFICIENCY ..............................................................................313
GIANT CELL ARTERITIS ...........................................................................314
HAEMODIALYSIS ..................................................................................317
HAEMOFILTRATION ................................................................................318
HYPERTENSION ....................................................................................319
INTRACEREBRAL HAEMORRHAGE ................................................................323
IRON-DEFICIENCY ANAEMIA .....................................................................324
MENINGITIS .......................................................................................326
METABOLIC NEUROPATHIES ......................................................................328
MIGRAINE ..........................................................................................329
MONONEURITIS MULTIPLEX ......................................................................331
MONONEUROPATHIES .............................................................................332
OSTEOARTHRITIS .................................................................................334
MECHANISMS OF DAMAGE TO PERIPHERAL NERVES ...........................................338
PERIPHERAL OEDEMA .............................................................................339
PERITONEAL DIALYSIS ............................................................................341
POLYNEUROPATHIES ..............................................................................342
RENAL TRANSPLANTATION .......................................................................343
RHEUMATOID ARTHRITIS ..................................................................(RA) 345
SEPTIC ARTHRITIS ................................................................................350
SUBARACHNOID HAEMORRHAGE ........................................................(SAH) 352
TENSION HEADACHE ..............................................................................355
THIAMIN (VITAMIN B1) DEFICIENCY ...........................................................356
TRANSIENT ISCHAEMIC ATTACKS (TIAS .......................................................) 357
CLINICAL PATTERNS OF UMN DISORDERS .....................................................359
VENOUS THROMBOEMBOLIC DISEASE ...........................................................361
VITAMIN B12 DEFICIENCY AND PERNICIOUS ANAEMIA .......................................363
........................................................................GENERAL SURGERY 366
ADULT UMBILICAL HERNIA .......................................................................367
ANTI-EMETIC DRUGS .............................................................................370
PROPHYLACTIC ANTIBIOTICS IN GUT SURGERY ................................................372
BLOOD GROUPS ...................................................................................373
BLOOD, BLOOD COMPONENTS AND BLOOD PRODUCTS ........................................374
COMPLICATIONS OF BLOOD TRANSFUSION .....................................................375
BURNS .............................................................................................377
PRINCIPLES OF FLUID AND ELECTROLYTE BALANCE ............................................379
HERNIA ............................................................................................382
INDICATIONS FOR REFERRAL TO ...........................................................ITU 391
PAIN AND ITS RELIEF .............................................................................392
POSTOPERATIVE CHEST INFECTIONS ............................................................394
POSTOPERATIVE CIRCULATORY COLLAPSE ......................................................396
POSTOPERATIVE MONITORING ...................................................................398
PRESSURE SORES .................................................................................400
PROCEDURE FOR BLOOD TRANSFUSION ........................................................402
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SCROTAL SWELLINGS .............................................................................403
WOUND HEALING .................................................................................409
WOUND MANAGEMENT ...........................................................................411
...................................................................................GI SURGERY 414
ACUTE APPENDICITIS .............................................................................415
ACUTE CHOLANGITIS .............................................................................417
ACUTE CHOLECYSTITIS ...........................................................................419
ACUTE PERITONITIS ..............................................................................421
LARGE BOWEL NEOPLASMS .......................................................................423
BILIARY COLIC ....................................................................................428
CANCER OF THE OESOPHAGUS ...................................................................429
CARCINOMA OF THE PANCREAS ..................................................................432
CARCINOMA OF THE STOMACH ...................................................................436
CHRONIC CHOLECYSTITIS ........................................................................439
COMMON BILE DUCT STONES ....................................................................440
INFLAMMATORY BOWEL DISEASE ................................................................441
DIVERTICULAR DISEASE ..........................................................................448
FAMILIAL ADENOMATOUS POLYPOSIS ...................................................(FAP) 450
GALLSTONE ILEUS ................................................................................451
GALLSTONES ......................................................................................452
INTESTINAL OBSTRUCTION .......................................................................454
OBSTRUCTIVE JAUNDICE .........................................................................456
SMALL BOWEL NEOPLASMS .......................................................................457
UPPER GI BLEEDS ................................................................................459
...............................................................RESPIRATORY MEDICINE 462
ACUTE RESPIRATORY DISTRESS SYNDROME .........................................(ARDS) 463
ASTHMA ............................................................................................466
BRONCHIAL CARCINOMA .........................................................................469
COR PULMONALE ..................................................................................473
CHRONIC OBSTRUCTIVE PULMONARY DISEASE ......................................(COPD) 478
HOW TO USE AN INHALER ........................................................................482
PLEURAL EFFUSION ...............................................................................483
PNEUMONIA .......................................................................................484
PNEUMOTHORAX ..................................................................................487
RESPIRATORY FAILURE ...........................................................................489
SARCOIDOSIS .....................................................................................492
TUBERCULOSIS .............................................................................(TB) 495
......................................................................VASCULAR SURGERY 499
ABDOMINAL AORTIC ANEURYSM ........................................................(AAA) 500
ARTERIOVENOUS MALFORMATION ......................................................(AVM) 502
CAROTID ARTERY DISEASE .......................................................................504
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CRITICAL LIMB ISCHAEMIA ...............................................................(CLI) 506
INTERMITTENT CLAUDICATION .............................................................(IC) 509
RAYNAUD’S PHENOMENON .......................................................................512
THE DIABETIC FOOT ..............................................................................515
TRAUMATIC ARTERIOVENOUS FISTULA ..........................................................516
VARICOSE VEINS ..................................................................................517
VASCULAR TRAUMA ...............................................................................521
VENOUS LEG ULCERATION .......................................................................523
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Anaesthetics
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Acute pain and the anaesthetist
Postoperative pain:
• This is best dealt with by preventing it happening in the first
place
• The patient who wakes up in severe pain following surgery can
be a difficult problem and the mainstay of dealing with this sort
of occurrence is the IV administration of opioid drugs (e.g.
morphine), larger doses of which may be necessary
Trauma pain:
• Anaesthetists are most likely to encounter a trauma patient in
pain when in the process of resuscitation or in preparation for
theatre
• It is important that analgesia in these circumstances does not
interfere with the resuscitation process or mask important
diagnostic signs in the patient
• For example, the use of IV morphine to treat a man with a
fractured femur, shock and head injury may lower his BP further,
depress his level of consciousness, interfere with neurological
observations and increase the risk of regurgitation and aspiration
of gastric contents
• It is still important to treat pain in these circumstances,
however, and a nerve block with local anaesthetics is often the
technique of choice
Labour pain:
• The pain of childbirth is, at its worst, one of the most severe
pains that can be experienced, and very few mothers are lucky
enough to go through labour without the need for some form of
analgesia
• Several features distinguish the pain of labour from the other
forms of pain:
o It gets worse, not better, with time
o It is non-pathological
o Is associated with a happy outcome
o Its relief must not result in compromise to the baby
o Its relief should not interfere with the ability of the mother
to share in the birth experience
• This means that the ideal pain relief in labour must be very
potent, very safe and not have any depressant effect upon the
CNS
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• This is where regional block, in the form of epidural or spinal
anaesthesia, comes into its own
Simple analgesic drugs:
• E.g. aspirin and paracetamol
• Are of little use when dealing with severe pain
• They are not strong enough and they can usually only be
administered orally, a route which is certainly not practical
following major surgery
• However, it is important not to forget these drugs in the
postoperative period; while recovery from painful surgery, most
patients need a ‘halfway’ drug to tide them over the period
between opioid usage and total freedom from pain
Non-steroidal anti-inflammatory drugs (NSAIDs):
• This wide-ranging group of drugs (used for many years to treat
arthritis and other musculoskeletal disorders) is now finding a
role in the management of postoperative pain
• Recent additions to the range (e.g. diclofenac and ketorolac)
have more powerful analgesic properties than their ancestors
• Can be administered by a variety of routes, including:
o IV
o IM
o Rectal
• Have well recognised side-effects, the most notorious being GI
irritation and haemorrhage
• They also interfere with platelet function and may exacerbate
asthma and renal failure
Opioids:
• Of the drugs available, morphine is the most commonly
prescribed in the UK. It has a duration of action of ~3-4 hours
following a single IM dose
• Diamorphine (heroin) is a powerful analgesic with some
advantages over morphine. However, its association with
addiction and abuse have, probably unfairly, somewhat
restricted its use
• Pethidine, used especially in labour, is slightly shorter-acting and
has atropine-like properties:
o Bronchodilation
o Tachycardia
o Reduction in secretions
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• Pethidine derivatives (e.g. fentanyl and alfentanil) are very
potent, short-acting opioids that tend to be used
intraoperatively, although they can be used postoperatively via
the epidural/spinal route
• Opioid drugs may be administered via a variety of routes:
o IM:
• Painful
• Lag time of ~20 minutes
• Only effective if the muscle is well perfused
o IV:
• No lag time
• Can be painlessly via an indwelling cannula
• The dose can be accurately titrated
• No reliance on adequate tissue perfusion
o Infusions:
• Designed to maintain a constant blood level of
analgesia
o Patient-controlled analgesia (PCA):
• A syringe is filled with a large quantity of morphine
and connected to the patient via an indwelling
cannula
• The patient is given a button which, when pressed,
delivers a fixed small dose of morphine
• The machine ‘locks out’ for a short period of time to
give the dose a chance to achieve its effect (usually
5 minutes), and then the patient may take another
dose if needed
• A typical prescription would allow 1mg of morphine
to be taken every 5 minutes, thus allowing the
patient up to 12mg/hour
o Epidural/spinal:
• R e c e p t o r s f o r o p i o i d s a r e f o u n d i n h i g h
concentrations in the spinal cord, and small doses of
these drugs can have profound analgesic effects
when administered into the epidural or intrathecal
(spinal) regions
• A dose of morphine as small as 0.2mg (1/50th
of the
IM dose) can produce highly effective pain relief for
24 hours following lower abdominal surgery
Side-effects of opioids:
• Sedation
• Respiratory depression
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• Nausea and vomiting
• Itching
• Urinary retention
• Histamine release
• Miosis
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Intermittent positive pressure ventilation (IPPV)
Overview:
• This is achieved by intermittently inflating the lungs with a
positive pressure delivered by a ventilator and applied via an
endotracheal tube or a tracheostomy
• A number of refinements and modifications of IPPV have been
introduced with:
o Positive end-expiratory pressure (PEEP)
o Intermittent mandatory ventilation (IMV)
o High-frequency jet ventilation (HFJV)
• The rational use of IPPV depends on a clear understanding of its
potential beneficial effects as well as its dangers
Beneficial effects of IPPV:
• Improved CO2 elimination
• Relief from exhaustion:
o Artificial ventilation removes the work of breathing and
relieves the extreme exhaustion that may be present in
patients with respiratory failure
• Effects on oxygenation:
o In those with severe pulmonary parenchymal disease, the
lungs may be very stiff and the work of breathing is
therefore greatly increased
o Under these circumstances, the institution of IPPV may
significantly reduce total body O2 consumption
Indications for IPPV:
• Acute respiratory failure
• Acute ventilatory failure
• Other indications:
o Prophylactic postoperative ventilation
o Head injury – to avoid hypoxia and hypercarbia which
increase ICP. Hyperventilation reduces ICP
o Trauma – chest injury and lung contusion
o Severe LVF with pulmonary oedema
o Coma with breathing difficulties (e.g. following drug
overdose)
Institution of IPPV:
• Requires endotracheal intubation
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• Intubating patients in severe respiratory failure is an extremely
hazardous undertaking and should only be performed by
experienced staff
• It extreme emergencies, it may be preferable to ventilate the
patient by hand using and oropharyngeal airway, a face mask
and a self-inflating bag until experienced help arrives
• The patient is usually hypoxic and hypercarbic, with increased
sympathetic activity:
o The stimulus of laryngoscopy and intubation can
precipitate dangerous arrhythmias and even cardiac arrest
o ECG and O2 saturation should be monitored
o Patient should be preoxygenated with 100% O2 before
intubation
o In some deeply comatose patients, no sedation will be
required but in the majority of patients, a short-acting IV
anaesthetic agent followed by muscle relaxation will be
necessary
• Endotracheal tubes can now be left safely in place for several
weeks and tracheostomy is, therefore, less often performed
• Tracheostomy may be required for the long-term control of
excessive bronchial secretions and/or to maintain an airway and
protect the lungs in those with impaired pharyngeal and
laryngeal reflexes
• Tracheostomy can be performed surgically, the trachea being
opened through the second, third and fourth tracheal rings via a
small transverse skin incision, or percutaneously using a
guidewire and a series of dilators
• Tracheostomy has a mortality rate of up to 3%
• A life-threatening obstruction of the upper airway that cannot be
bypassed with an endotracheal tube should have a
cricothyroidotomy
Dangers of IPPV:
• Airway complications
• Disconnection, failure of gas or power supply, mechanical faults
• CVS complications:
o The intermittent application of positive pressure impedes
venous return and distends alveoli, thereby ‘stretching’ the
pulmonary capillaries and causing a rise in pulmonary
vascular resistance
o This produces a fall in cardiac output
• Respiratory complications:
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o V/Q mismatching
o Collapse of peripheral alveoli
o Secondary pulmonary infection
• Barotrauma:
o Pneumothorax
o Pneumomediastinum
o Pneumoperitoneum
o Subcutaneous emphysema
• GI complications:
o Abdominal distension associated with an ileus
o Unknown cause
• Salt and water retention:
o Increases secretion of ADH
o Decreases secretion of ANP
o The fluid retention is often particularly noticeable in the
lungs
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Preoperative grading
A commonly used grading system is that described by the American
Society of Anaesthesiologists (ASA), in which patients are allocated to
one of five categories
The scoring system allows easier communication between
anaesthetists and is a useful research tool
However, it gives only limited prognostic information about the
chances of an individual surviving an operation
Significant factors (including the type of procedure, a history of
difficult intubation and of obesity) are not included in the classification
Preoperative grading system of the ASA:
ASA I Healthy patient
ASA II Mild systemic disease, no functional disability
ASA III Moderate systemic disease, functional disability
ASA IV Severe systemic disease, constantly life-threatening
ASA V Moribund patient, unlikely to survive 24 hours with or
without an operation
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Local and regional anaesthesia
Definitions:
• Local anaesthesia:
o The use of a drug to produce anaesthesia by topical
application, infiltration or ring block
• Regional anaesthesia:
o Is a term reserved to describe major nerve blocks or
spinal/epidural techniques
o However, the terms are often used interchangeably
Regional versus general anaesthesia:
Advantages Disadvantages
Avoids adverse effects of general
anaesthetic agents:
• Respiratory depression
• CVS depression
• Nausea/vomiting
• ‘Hangover’
Toxicity of local anaesthetic drugs
Avoids potential hazards of
unconsciousness:
• Loss of airway
• Aspiration
• Damage to joints through
malpositioning
Often difficult techniques:
• More risk of failure or partial
success
• More discomfort while
performing block
• May take longer to establish
Minimises endocrine stress
response to surgery
Greater co-operation needed from
patient
Decreased postoperative pain Sets time limit for surgery
Earlier discharge from hospital Restricts flexibility of surgeon if
operation needs to be more
extensive
Hazards of local anaesthetic agents:
• Local administration:
o Inadvertent IV injection - rapid onset of toxic effects
o Inadvertent intraneuronal injection - nerve damage
o Incorrect use of adrenaline –containing solution - tissue
necrosis
o Vasodilatation - increased bleeding
o Tachyphylaxis - reduced effectiveness of repeated doses
o Spread of infection - if injected into infected area
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• Regional anaesthesia:
o Marked vasodilatation – fall in BP
o Major nerve compression – haematoma or abscess
formation
o Large doses may be needed – risk of overdosage
• Effects of overdose:
o CVS:
• Bradycardia
• Fall in cardiac contractility – hypotension
• Cardiac arrest
• NB: Cocaine and adrenaline-containing solutions cause
tachycardia and hypertension
o CNS:
• Paraesthesiae (especially around the mouth)
• Anxiety
• Tremors
• Fitting
• Coma
Types of local anaesthesia:
• Topical anaesthesia:
o Throat lozenges
o ENT procedures
• Infiltration:
o A&E
o Minor surgery
• Ring block:
o Is a quick and effective method of anaesthetising an
extremity (typically a finger or toe)
• Nerve blocks
• IV regional anaesthesia (IVRA or Bier’s block):
o Used to anaesthetise the arm (or occasionally the leg),
classically before reduction of a fractured wrist
o Also used for minor surgery (e.g. relief of carpal tunnel
syndrome)
• Spinal and epidural anaesthesia
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Breast Surgery
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Benign breast pain
Benign breast pain is either cyclical or non-cyclical
The first follows the pattern of the menstrual cycle; the second is
random in timing
Cyclical pain:
• Most commonly affects women <35 years of age
• Onset is during the early phase of the cycle; intensity gradually
worsens to reach a peak just before menstruation, easing with
the start of the period
• In mild cases, the pain affects the upper outer quadrants of the
breasts
• In severe cases, the whole breast may feel engorged, tender and
heavy and physical contact can be unbearable
• Post-menopausal women on HRT can get cyclical breast pain
• Examination:
o Tenderness and a firm nodular feel in the upper outer
quadrants of the breast
Investigation of cyclical breast pain:
• In the presence of a typical history of bilateral cyclical pain,
there is often little reason to embark on any investigations
Management of cyclical breast pain:
• The most important aspect is reassurance that the condition is
entirely benign and is not associated with either carcinoma or a
tendency to its development in later life
• Many women are content to live with their discomfort if they can
be reassured on both these counts
• Three drugs are commonly used:
o Gamma-linoleic acid (evening primrose oil):
• 320mg daily po
• An essential fatty acid
• Thought to render breast cells less sensitive to the
effects of sex hormones
• 60% of sufferers experience relief
• Needs to be taken for 3-4 months before relief is
experienced
o Danazol:
• 200-300mg daily po
• Interferes with the action of oestrogen on breast tissue
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o Bromocriptine:
• Gradually increasing doses up to a maximum of 5mg
daily po
• Blocks the pituitary drive to produce FSH and LH
o Bromocriptine and Danazol can cause menopausal-like
symptoms
Non-cyclical pain:
• May be intermittent or constant and is confined to localised
areas of one breast
• It can be caused by conditions both within and without the
breast, including:
o Mammary duct ectasia
o Periductal mastitis
o Trauma
o Tietze’s disorder – characterised by tenderness over
costochondral junctions
• It is often difficult to identify a specific cause of non-cyclical pain
Investigation of non-cyclical breast pain:
• As with cyclical breast pain, investigation in those <35 years of
age is limited to clinical assessment
• In older women, mammography is often a wise precaution,
particularly if the pain is consistently localised to one spot or is
associated with a lump
• 10% of patients with such features have an underlying
carcinoma
Management of non-cyclical breast pain:
• Is much more resistant to treatment than is cyclical pain
• The following may be helpful:
o Simple NSAIDs
o Treatment of inflammatory conditions
o Local lignocaine/steroid injection
• Most patients end up having to live with their pain until it
resolves by itself, which in the great majority it eventually does
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Breast lumpiness and lumps
Lumpiness:
• Can present on its own but is frequently associated with cyclical
breast pain
• It is a manifestation of the cyclical changes that go on in the
female breast during the menstrual years
• A variety of descriptive terms have been applied to it:
o Fibroadenosis
o Cystic mastopathy
o Fibrocystic disease
o Cystic mastitis
• All are merely descriptive of the changes seen to a varying
degree on histological examination and do not give any insight
into cause
Discrete single lump:
• The commonest causes of a lump are:
o Fibroadenoma
o Cyst
o Very localised fibroadenosis
• The fear uniting them all is the well-defined nature of the lump
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Cysts
Epidemiology and aetiology:
• Occurrence is usually after 35 years of age and up to the
menopause
• There has been some suggestion that multiple recurrent cysts
are associated with an increased tendency to breast cancer
Clinical features:
• The history is of a palpable and occasionally tender lump
• Physical findings are of a tense, discrete, mobile lump anywhere
in the breast
Investigation and management:
• Whenever a clinical diagnosis is made of a cyst, needle
aspiration should be done at once:
• It yields straw-coloured fluid and causes collapse of the cyst
• Equally important, it immediately reassures the patient, although
there have to be some exceptions:
o Failure of the lump completely to disappear
o Bloodstained aspirate
• Failure to disappear completely:
o Re-evaluation must take place within a few weeks
o A persistent lump must be evaluated by mammography
and either be subject to FNAC or excised for histological
examination
• Bloodstained aspirate:
o The simple cause is traumatic aspiration
o However, this must be confirmed by cytological
examination of the aspirate and mammography
o Clinical reassessment, re-aspiration if a lump is present or
excision biopsy is then the appropriate course
• Multiple cysts:
o Some patients have multiple cysts identified at
mammography or which present clinically as a lumpy
breast
o Danazol can be helpful in reducing the incidence of clinical
recurrence
o Given the possible risk of carcinoma, follow-up with
mammography is necessary
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Duct papilloma
This is a relatively uncommon lesion
Clinical features:
• There is a serous or bloodstained discharge from a single aspect
of the nipple, although the patient may not realise that the
discharge is localised
• Other symptoms are rarely present
• The breast is normal, but there is either the spontaneous
appearance of discharge from one aspect of the nipple or
‘milking’ of a segment produces nipple discharge from the duct
draining that segment
Investigations:
• The main concern, particularly if the discharge is bloodstained, is
that occasionally there is an underlying malignancy, although
duct papilloma is benign
• Investigations are the same as for mammary duct ectasia
• In spite of negative cytological findings, it is nearly always
necessary (in a bloodstained single duct discharge) to excise the
involved system to establish that a papilloma is present
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Fibroadenoma
These tend to affect younger women and are infrequent after about
35-40 years of age
Pathological features:
• Many remain static
• A small proportion either regress or increase in size
• In developing countries, they may reach a mass larger than the
breast in which the growth occurs
Clinical features:
• Generally the patient discovers a painless lump
• Well-defined lump
• Consistency is rubbery to firm or hard
• There is much mobility (it may be difficult to find) – hence the
nickname ‘breast mouse’
• As with any lump, they should be subjected to triple
assessment:
o Clinical examination
o Imaging
o Cytology
• Provided all these support a diagnosis of fibroadenoma, small
lesions can be left alone
• Larger lesions (>4cm) or those in older women may be better
removed
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Fibroadenosis
History:
• Usually, the upper outer quadrants are affected but, as with
pain, one side alone may be involved
• Young
• Often in the early years after the menarche
Physical findings:
• May be single or multiple lumps in one or both breasts
• May be acutely tender (particularly premenstrually)
Investigations:
• Mammography:
o Is indicated in those >40 years of age
o In a lumpy breast, the appearances are those of dense
fibrosis with micro- or macrocystic change
• Ultrasound:
o Indicated in those <40 years of age
o May show cystic changes
• Fine needle aspiration cytology (FNAC):
o Suspicious areas are aspirated under image control
o Typical findings are of benign cells
Management:
• Reassurance that the changes are part of the normal spectrum
of the breast’s response to female sex hormones
• If there is associated pain in a large breast, firm support may
help
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Galactorrhoea
This is a rare cause of bilateral milky discharge
It follows lactation and is caused by a persistent elevation of prolactin
Management:
• Bromocriptine is used until the discharge subsides
• Prolactinomas should be considered in long persistent discharge,
but are rare
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Infection of the breast
There are 2 common causes of infection:
• Lactational breast abscess
• Periductal mastitis
Lactational breast abscess:
• Is a complication of lactation and breast-feeding
• The organism involved is nearly always Staphylococcus aureus
• It is believed that the bacteria get into the breast tissue through
cracks in the nipple during feeding
• The abscess may break through into neighbouring segments and
thus become multilocular
Clinical features of a lactational breast abscess:
• History:
o The baby may be anything from a few days to some
months old
o The mother may have noticed an obvious crack in the
nipple (although this is unusual)
o Segmental pain in the affected breast rapidly becomes
severe and sleep is often lost
• Physical findings:
o A tender red segment in the breast is seen
o May be evidence of nipple damage (i.e. a crack in its
surface)
o Fluctuation is not a feature unless the abscess is advanced
and beginning to point towards the skin, which may
ultimately show evidence of necrosis
Management of a lactational breast abscess:
• If detected and treated early, acute mastitis can resolve
• Anti-staphylococcal antibiotics are prescribed in full dose
• If the nipple is obviously damaged, feeding on this side is
stopped and the milk expressed from the healthy segments
• Continued pain and loss of sleep suggest that there is an abscess
which, in its early stages, can be aspirated with a wide-bore
needle under LA
• Ultrasound is a useful means of determining whether there is
any pus to drain
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Periductal mastitis:
• This condition affects young women in their 30s and is
associated with smoking
• Is characterised histologically by a low-grade inflammatory
response around the ducts adjacent to the nipple
• The bacteria involved are nearly always anaerobes
Clinical features of periductal mastitis:
• Tenderness develops on one aspect of the areola
• There is rarely any systemic disturbance
• Recurrent bouts may occur before the patient seeks medical
attention
• A tender swelling at the edge of the areolar is seen, which may
progress to abscess formation with a periareolar sinus and
discharge
Investigation and management of periductal mastitis:
• Because there may be a discrete mass with only a few, if any,
characteristics of inflammation, FNAC and mammography may
be necessary to exclude an underlying carcinoma
• Inflammatory swellings may respond to antibiotics
• Once an abscess has formed – drainage is required
• A complication of abscess is the formation of a mammary duct
fistula:
o Discharges intermittently
o May be associated with recurrent abscess formation
o The duct segment must then be excised because, in the
presence of a duct abnormality, attempts to eradicate
sepsis with antibiotics are usually futile
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Mammary duct ectasia
Aetiology and pathological features:
• The cause, as with many breast disorders, is an exaggeration of
the normal cyclical changes – a wear and tear process
• The ducts adjacent to the nipple become dilated and engorged
with breast secretions
• Secondary infection and a retroareolar abscess may form, but
even if this does not happen, fibrosis can cause nipple retraction
History:
• The discharge can range from milky to dirty green
• Is often (but not always) bilateral
• Occasionally it is associated with pain, usually cyclical
• Acute infection causes pain and swelling
Physical findings:
• The breast may have features of lumpiness
• Nipple retraction:
o Caused by the chronic inflammation often associated with
this condition
o Slit-like appearance
o May be confused with carcinoma
• In acute inflammation, an abscess forms which, if not treated at
am early stage, discharges at the areolar margin:
o A small sinus (mammary fistula) then results which can be
the focus of further attacks of inflammation
• If qualified by age, patients should have a mammogram to
establish the general state of the breast
• Discharge is sent for cytological assessment
• Provided both the above investigations are normal, nothing
further needs to be done other than to reassure the patient
• If a discharge is very troublesome, excision of the duct system
(Hadfield’s operation) provides symptomatic relief
Abscess:
• An abscess in this condition is followed by a mammary fistula
• In consequence, after drainage there is not only often a
persistent discharge but also the risk of recurrence
• The involved duct and its drainage area should be excised
electively
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Nipple discharge
There are 3 common causes:
• Mammary duct ectasia
• Duct Papilloma
• Galactorrhoea
An important point to establish is whether the discharge is from a
single or multiple ducts
That from a single duct, particularly if bloodstained, is more likely to
be associated with a Papilloma
Discharges are commoner in women over 35 years of age
In younger women, they may be associated with the OCP
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Trauma to the breast
Overview:
• Trauma to the breast is relatively rare, although sexual
encounters and love bites may be responsible for local injury
• A blunt impact can interfere with local blood supply and,
together with a haematoma, cause fat necrosis
• Another cause is the use of therapeutic anticoagulants in
patients with very large and pendulous breasts in which very
minor trauma may precipitate extensive haemorrhage which
may go on to necrosis
Clinical features:
• Fat necrosis causes a hard, painful lump, usually following a
story of minor local trauma
• A hard lump is often found, with some irregularity and
occasionally tethering to the overlying skin
• The appearances are suggestive of a carcinoma but the condition
can usually be distinguished because of the history of trauma,
associated bruising and resolution of the lump with observation
• Investigation is the same as for any discrete lump
• The condition resolves with time and specific treatment is not
required
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Cancer Medicine
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Acute leukaemias
Clinical features:
• The symptoms of acute leukaemia are a consequence of bone
marrow failure:
o Symptoms of anaemia:
• Tiredness
• Weakness
• Exertional dyspnoea
o Repeated infections
• There may be few or no abnormal physical signs; but patients
often have:
o Signs of anaemia
o Bruises, petechial haemorrhages, purpura, fundal
haemorrhages
o Signs of infection
o Occasionally, lymph node enlargement and/or
hepatosplenomegaly
Investigations:
• FBC:
o Low Hb
o WCC (may be raised, normal or low)
o Thrombocytopenia
• Peripheral blood film:
o Shows characteristic leukaemic blast cells
• Bone marrow aspirate:
o Shows increased cellularity with abnormal lymphoid or
myeloid blast cells
General principles of management:
• Before starting treatment, the following points must be
considered:
o Correction of anaemia and thrombocytopenia with the
administration of blood and platelets
o Infection should be treated with IV antibiotics
o Leukaemic blast cells can infiltrate the brain and lungs –
resulting in coma and respiratory failure respectively
o If the blast cell count in the peripheral blood is very high
(>100x109
/L) the patient may need leucophoresis:
• Blood is collected from a vein and centrifuged so as to
remove leukaemic cells, and the RBCs and plasma are
then returned to the patient via another vein
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• Leucophoresis can be life-saving
o In certain types of leukaemia, where the rate of cell
division is very fast (e.g. B-cell and T-cell ALL), patients
may develop a ‘tumour lysis’ syndrome when
chemotherapy is given:
• Hypercalcaemia
• Hyperphosphataemia
• Hyperkalaemia
• All resulting from a high rate of cellular breakdown
• Is potentially life-threatening and difficult to treat
once it has occurred
Classification:
• Leukaemia can be divided on the basis of the speed of evolution
of the disease into acute or chronic
• Each of these is then further subdivided into myeloid or
lymphoid, according to the cell type involved. Hence the terms:
o Acute myelogenous leukaemia (AML)
o Acute lymphoblastic leukaemia (ALL)
o Chronic myeloid leukaemia (CML)
o Chronic lymphocytic leukaemia (CLL)
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Acute lymphoblastic leukaemia (ALL)
Overview:
• Predominantly a disease of children
• Is potentially curable
• 90% of children respond to treatment and 50-60% are cured
• The cure rate in adults is only about 30%
Treatment:
• The principles of initial treatment are the same as those for AML
• Cyclical chemotherapy comprising:
o Vincristine
o Prednisolone
o L-asparaginase
o Doxorubicin
• The sequence of treatment, however, is different to AML because
ALL has a propensity for involvement of the CNS, thus treatment
includes prophylactic intrathecal drugs (e.g. methotrexate)
• Most patients receive oral maintenance therapy for 2-3 years
Treatment at recurrence:
• A proportion of patients are cured with the initial therapy
• In the rest, the disease recurs and ultimately proves fatal unless
a second remission can be achieved (high-dose treatment and
some form of transplant procedure)
• With such treatment, a further 20-30% of patients will survive
long-term
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Acute myelogenous leukaemia (AML)
Overview:
• AML is a potentially curable disease
• More common in older adults
• Is classified on the basis of the morphological appearance of the
bone marrow into 7 subtypes (M1-M7), which differ by virtue of
the predominant cell type involved
Treatment:
Treatment has traditionally been divided as being in 2 parts –
remission induction (complete remission, CR) and post-remission/
consolidation therapy
• The reason for the continuation of therapy post-remission is as
follows:
o At the point of CR (when there is no morphologically
detectable leukaemia) there are still 108
or109
leukaemic
blast cells present.
o It is, therefore, not surprising that if no post-remission
therapy is given, the majority of patients develop recurrent
leukaemia
• Induction of remission is via chemotherapy:
o An anthracycline drug (e.g. doxorubicin) in conjunction
with cytarabine, with or without another drug (e.g.
etoposide)
o Patient needs to stay in hospital for 4 weeks in the first
instance owing to the risk of infection and bleeding
consequent upon neutropenia and thrombocytopenia
o Subsequent cycles of treatment are given on an outpatient
basis
• Options for post-remission therapy include:
o Further cycles of the same chemotherapy used to induce
remission
o Chemotherapy different from that given to induce
remission
o Myeloablative therapy with allogeneic/autologous bone
marrow transplantation (BMT)
Prognosis:
• Approx. 70% of patients <60 years of age will return to normal
health
• However, within 1-3 years the disease will recur in at least 60%
(the remainder almost certainly having been cured
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• In younger patients with a recurrence, cure is still possible for a
proportion, using myeloablative therapy with allogeneic/
autologous haemopoietic progenitor cell support (HPCS)
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Acute promyelocytic leukaemia (APML)
Is a subtype of AML (M3 subtype)
Clinical features:
• Has a specific association with disseminated intravascular
coagulation (DIC)
• Patients may present with severe bleeding which worsens when
treatment is started as the leukaemic blast cells break down,
leading to further consumption of clotting factors and platelets
Treatment:
• Regular, twice daily platelet transfusion and maintenance of the
fibrinogen level with FFP as the chemotherapy is given
• Provided that remission can be achieved, patients with APML
have a better overall prognosis than patients with other subtypes
of AML
• Oral ATRA (all-trans-retinoic acid) can lead to achievement of CR
in most patients with APML
• Unfortunately, these remissions are not durable and, therefore,
they must be consolidated with conventional chemotherapy
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Breast cancer
Epidemiology:
• Most commonest form of cancer to affect women in the Western
world
• Directly responsible for 19% of all female cancer-related deaths
• Incidence of 30 per 100,000 population
• It is estimated that 1 in 9 women will develop the disease
Aetiology:
• The risk factors include:
o Age:
• Rare <35 years of age
• Incidence increases with age
o Country of birth:
• High risk = northern Europe and north America
o Genetic factors:
• Hereditary and familial breast cancer can be
described using the Lynch system of classification
(see below)
o Early menarche/late menopause
o Nulliparity/late childbirth
o Obesity
o Exogenous hormones:
• High-dose OCP
• HRT
o Previous cancer
o Irradiation
o Previous benign disease (see below)
The lynch classification of inherited susceptibility to breast cancer:
• Hereditary breast cancer:
o A family history of breast cancer and, sometimes, related
cancers (colonic, endometrial) forming part of the Lynch
syndrome type II
o This involves an autosomal dominant, highly penetrant
cancer susceptibility factor
o These patients tend to be younger than average, have
multiple primaries and may also have other tumours
• Familial breast cancer:
o A family history of breast cancer including one or more
first or second degree relative with breast cancer that does
not fit the hereditary breast cancer definition
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o Relative risk of developing breast cancer in relation to
previous benign beast disease:
• No risk:
• Apocrine change
• Ductal ectasia
• Mild hyperplasia (no atypia)
• Slight risk:
• Moderate or florid hyperplasia (no atypia)
• Sclerosing adenosis
• Papilloma
• Moderate risk:
• Atypical ductal or lobular hyperplasia
TNM classification of breast cancer:
Tis Carcinoma in situ (pre-invasive)
T0 No clinical evidence of primary tumour
T1 Tumour <2cm
T2 Tumours 2-5cm
T3 Tumour >5cm
T4 Tumour of any size but with direct extension to chest wall or
skin:
o (a) Fixation to chest wall
o (b) Oedema, lymphocytic infiltration or ulceration
of skin
o (c) Both (a) and (b)
N0 No palpable ipsilateral axillary lymph nodes
N1 Palpable nodes not fixed:
o inflammatory only
o containing tumour
N2 Fixed ipsilateral lymph nodes
N3 Ipsilateral supraclavicular/infraclavicular nodes or oedema of the
arm
M0 No evidence of distant metastasis
M1 Evidence of distant metastasis
Histology:
• Are usually adenocarcinomas and are divided into 2
types:
o Ductal
o Lobular
• There are 3 degrees of differentiation:
o Grade I – well differentiated
o Grade II – moderately differentiated
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o Grade III – poorly differentiated
Carcinoma in situ:
This term refers to the period during which normal epithelial cells
undergo apparent malignant transformation but do not invade through
the basement membrane
• There are 2 forms:
o Lobular (LCIS)
o Ductal (DCIS). DCIS represents all types of in situ
carcinoma that are not identified as lobular. It can be
further subdivided into:
• Comedo (a particularly menacing type of Tis)
• Solid
• Cribiform
• Micropapillary
• The ratio of DCIS to LCIS is approximately 3:1 with 10-37% of
those with LCIS and 30-50% of those with DCIS going on to
develop invasive carcinoma
Types of invasive breast carcinoma:
Ductal 80%
Lobular/ductal combined 5%
Medullary 6%
Colloid 2%
Other 2%
Symptoms:
Lump 76%
Pain 5%
Nipple retraction 4%
Nipple discharge 2%
Skin retraction 1%
Axillary mass 1%
Paget’s disease:
• This condition presents clinically as a chronic, eczematoid
eruption of the nipple
• The diagnosis may be confused with eczema
• It constitutes ~2% of the histological types
• Is almost always associated with an underlying intraductal or
invasive carcinoma
Comparison of Paget’s disease and eczema of the nipple:
Paget’s disease Eczema
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Unilateral Bilateral
Progressive/continuous Intermittent/variable
Moist or dry Moist
Irregular/discrete Indistinct
Nipple always involved Nipple sparing
Pruritus absent Pruritus present
Inflammatory breast carcinoma:
• Comprises ~1% of breast carcinomas
• Is rapidly progressive
• Characterised by:
o Erythema
o Peau d’orange
o Skin ridging
o May/may not be a palpable mass
• The commonest presenting feature is pain (unlike other breast
cancers)
• The characteristic appearance of a diffusely enlarged breast is
consequent upon the dissemination of tumour cells through the
lymphatics of the dermis
Establishing the diagnosis of breast cancer:
• Any palpable breast abnormality should be assessed by the
process of triple assessment:
o Clinical evaluation
o Radiological evaluation
o Cytological/histological evaluation
• During the consultation with the patient, it is important to
convey that only 20% who consult have a breast carcinoma
Physical examination:
• The patient must be undressed to the waist and should sit facing
the examiner
• The breast is initially examined from the front with the arms first
at the side, then raised above the head and finally placed on the
hips
• The patient is asked to point out the supposed area of
abnormality and this is examined first
• The following must always be assessed:
o Asymmetry
o Visible lumps
o Erythema
o Peau d’orange (cutaneous oedema)
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o Contour flattening
o Skin tethering (as identified by puckering, particularly
when the arms are raised)
o Abnormal fixation
o Retraction and altered axis of the nipples
• After this, the patient is asked to lean forward, once again
looking for skin retraction
• The supraclavicular, infraclavicular and axillary lymph nodes
should be examined
• Further palpation of the breast is best performed in the supine
position
• Should a mass be felt, one must assess its:
o Size
o Shape
o Location
o Fixation
o Consistency
Mammography:
• Mammography is not useful in women <35 years of age:
o Dense breasts which may mask an underlying tumour
o Interpretation very difficult
o However, should be done if there is clinical suspicion of a
malignancy
• Mammographic abnormalities that warrant further investigation
include:
o Radiological masses undetected on clinical examination
o Microcalcifications
o Stellate densities
o Architectural distortion
o Change from a previous mammogram
• Mammography has a false-negative rate of 10-15%
Ultrasound:
• Very good at discriminating between solid and cystic masses
• Useful for guiding biopsy
• In younger women, ultrasound may reveal more information
than mammography and most surgeons would perform this test
first in women <35 years of age
• Masses in fatty breasts are difficult to assess
Aspiration cytology:
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• Needle aspiration of a breast lump is dine with a 21-gauge
needle
• The contents of the needle are expressed on to a slide, smeared
and fixed (often in both air and alcohol) for cytological
examination
• Is a false-negative rate of 1%
Wide-bore core needle biopsy:
• This method provides a sample of tissue for histological, rather
than cytological examination
• Because the results are more reliable, this procedure is rapidly
superseding aspiration cytology
Open biopsy – requires a general anaesthetic:
• Excision biopsy:
o Refers to the removal of all gross evidence of disease with
a small rim of normal breast tissue
• Incision biopsy:
o Similar to excision biopsy, except that only a part of the
lump is removed
o It is generally felt that this is not good surgical practice
and is, therefore, restricted to larger tumours
o Has largely been superseded by wide-bore core needle
biopsy
Nipple biopsy:
• Conditions affecting the nipple (especially an eczema-like
appearance) often warrant biopsy
• A wedge of nipple-areolar complex can be excised under local
anaesthetic with minimal cosmetic disruption to confirm or refute
a diagnosis such as that if Paget’s disease
Management of carcinoma in situ:
• DCIS is usually unilateral and is often treated by surgical
excision and postoperative radiotherapy
• LCIS is a marker for a disease that is often bilateral and only
sometimes progresses to invasive ductal carcinoma. Therefore,
the patient can elect to be observed closely or undergo a
curative bilateral mastectomy
• Less than 1% of axillary lymph nodes will be affected and
clearance is not required
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Management of invasive carcinoma:
• This varies widely and is largely dependent on the size of the
tumour and whether or not there is regional lymph node
involvement
• Generally:
o Wide local excision of tumour, either a:
• Lumpectomy
• Quadrantectomy (removal of the involved breast
quadrant)
o Local radiotherapy
o Possible axillary lymph node clearance
o Possible adjuvant chemotherapy
• For more advanced disease:
o Radical mastectomy with axillary node clearance
o Radiotherapy
o Adjuvant chemotherapy
Complications of surgery:
• Haemorrhage/haematoma formation
• Infection
Complications of radiotherapy:
• Cutaneous inflammation
• Photosensitisation
• Fibrosis and distortion of breast shape
• Shoulder stiffness
• Brachial plexus damage
• Lymphoedema of the arm
Adjuvant therapy:
• This encompasses both cytotoxic and hormonal therapy
• Cytotoxic therapy:
o Are 2 main regimens:
• CMF (cyclophosphamide, methotrexate and 5-
fluorouracil)
• CAF (cyclophosphamide, adriamycin and 5-
fluorouracil)
o Chemotherapy is given to all patients at a high risk of
recurrence
• Hormonal therapy:
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o ~30% of all breast tumours respond to an anti-oestrogen
such as tamoxifen 20mg od, this rises to 60% of
oestrogen-receptor positive tumours
o Some tumours are resistant to tamoxifen and even
respond unfavourably, therefore, alternative hormonal
therapies are available:
• Aromatase inhibitors (prevent the conversion of
androgens to oestrogen) such as formestane and
Anastrozole
• Surgical oophorectomy
• Chemical oophorectomy (using Gn-RH agonists)
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Cancer genetics
Overview:
• The development of cancer is associated with a fundamental
genetic change with the cell
• Evidence for the genetic origin of cancer is based on the
following:
o Some cancers show a familial predisposition
o Most known carcinogens induce mutations
o Susceptibility to some carcinogens depends on the ability
of cellular enzymes to convert them to a mutagenic form
o Genetically determined traits associated with a deficiency
in the enzymes required for DNA repair are associated with
an increased risk of cancer
o Some cancers are associated with chromosome ‘instability’
o Malignant tumours represent clonal proliferations of
neoplastic cells
o Some tumours contain mutated oncogenes
• Mutations may occur in the germline and can, therefore, be
present in every single cell in the body, or they may occur in a
single somatic cell and be present only in the tumour following
clonal proliferation
Cytogenetic (chromosome) abnormalities:
• Chromosome changes are often reciprocal translocations
• A non-reciprocal change results in deletion or addition of part of
a chromosome
• Examples of specific chromosome changes associated with
malignancy are:
o Chronic myeloid leukaemia (CML):
• 95% of patients have a reciprocal translocation
between chromosome 22 and chromosome 9
o Acute promyelocytic leukaemia (APML):
• Almost all patients have the chromosome translocation
t(15;17)
o Burkitt’s lymphoma:
• The most frequent change is a reciprocal translocation
between chromosomes 8 and 14
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DNA repair:
• Some autosomal recessive diseases associated with
abnormalities of DNA repair predispose to the development of
cancer:
o Xeroderma pigmentosa (XP):
• Inability to repair DNA damaged by UV light and some
chemicals, therefore leading to a high incidence of skin
cancer
o Ataxia telangectasia (AT):
• These patients have a high sensitivity to ionising
radiation and have an increased incidence of lymphoid
tumours
o Bloom’s syndrome (BS):
• Increased incidence of lymphoid tumours
o Fanconi’s anaemia (FA):
• Increased incidence of lymphoid tumours
Inherited cancers:
• The following are examples of cancer syndromes that exert
dominant inheritance:
o Retinoblastoma:
• An eye tumour found in young children
• May be inherited (40%) or acquired (60%)
• Those with the inherited form have a germline mutation
of the long arm of chromosome 13
o Breast and ovarian cancer:
• 2 genes have been identified – BRCA1 and BRCA2
• These mutations account for most cases of familial
breast cancer and 50% of ovarian cancers
o Wilm’s tumour
o Familial adenomatous polyposis (FAP)
o Neurofibromatosis
o Multiple-endocrine-adenomatosis syndromes (MENS)
Oncogenes:
• Normal cells contain genes known as proto-oncogenes,
activation of which (for example by a mutation or carcinogen to
produce an oncogene) would result in malignant transformation
• It has been demonstrated that specific proto-oncogenes are
associated with specific cancers
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Palliative care in cancer patients
GI symptoms:
• The most frequent symptoms are:
o Anorexia
o Malaise
o Weakness
• Current research suggests that endogenously produced
cytokines (e.g. TNF and ILs) are mediators of the anorexia/
cachexia syndrome
• Nausea and vomiting:
o Occurs in up to 2/3 of cancer patients in the last 6 weeks
of life
o In order to ensure adequate absorption of the antiemetic,
parenteral administration (preferably SC) may be helpful
for the first 24-48 hours
• Antiemetics are classified according to their affinities for NT
receptor sites:
o A prokinetic DA antagonist (e.g. metoclopramide 10mg
tds) would be helpful in vomiting due to upper GI stasis or
liver metastases
o Prokinetics should be avoided in cases of intestinal
obstruction, as they increase peristalsis in the upper bowel
o Centrally acting anticholinergics (e.g. cyclizine 50mg tds)
or centrally acting DA antagonists (e.g. haloperidol 1.5mg
tds) are the drugs of choice in vomiting caused by drugs or
metabolic disturbance
o As with the prescription of analgesics, antiemetics will be
most effective if prescribed on a regular, rather than ‘as
required’ basis
Bowel obstruction:
• May present acutely or in a more chronic manner
• The cause is often multifactorial
• A small number of patients may benefit from surgical
intervention
• Most patients will not be suitable for surgery and can be
managed medically
• The active medical management of malignant bowel obstruction
includes:
o The relief of intestinal colic using an antispasmodic (e.g.
hyoscine butylbromide 60-80mg daily)
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o Treating continuous pain with adequate analgesia (e.g.
diamorphine)
o Treating vomiting if nausea is a problem with a centrally
acting antiemetic (e.g. cyclizine 150mg daily or haloperidol
5-10mg daily)
• It will be necessary to administer all of the above medications
parenterally (the SC route is most appropriate)
• Patients may be allowed to drink and eat low-residue diets which
are mostly absorbed in the proximal GI tract
Respiratory symptoms:
• In particular, dyspnoea
• Management is based on accurate diagnosis of the cause and
active treatment of all potentially reversible situations:
o Treat infections
o Drain pleural/pericardial effusions
o Transfuse symptomatic anaemia patients
• The sensation of dyspnoea and a cycle of respiratory panic may
be partially relieved by the prescription of regular
benzodiazepines
• Regular doses of short-acting opioids (5-20mg qqh) are also
helpful
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Carcinoma of the bronchus
Aetiology:
• Tobacco:
o Latent period of 10-30 years
o The primary determinants are:
• Number of cigarettes consumed
• Age of onset of smoking (those under 16 years of
age at start have irreversible damage to their
bronchial genetic makeup
• Length of time of smoking
• Type of tobacco (cigarettes or pipe, filter or non-
filter)
• Passive exposure to tobacco smoke
o Asbestos exposure
o Irradiation
o Toxic metals
o Certain chemicals
Types of bronchial carcinoma:
• Squamous cell carcinoma (SCC)
• Adenocarcinoma
• Small cell carcinoma (oat cell carcinoma)
• Alveolar cell or bronchoalveolar carcinoma
Squamous cell carcinoma:
• 60% of all lung tumours
• Associated with smoking and is rare in non-smokers
• Squamous metaplasia -> carcinoma in situ -> invasive
carcinoma
Adenocarcinoma:
• 15% of lung tumours
• Has a tendency to be more peripheral, arising in the small
bronchial glands
• Most common in women
• Is the type seen in non-smokers
Small cell (oat cell) carcinoma:
• Arises from the Kulchitsky chromaffin cells
• Highly malignant
• Hormone production by the tumour is common
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• A benign form of a small cell carcinoma is a carcinoid tumour
Alveolar cell carcinoma:
• Arises in the distal airways
• Often diffuse, multifocal and bilateral
• Resistant to radio-/chemotherapy
• Very poor prognosis
Symptoms:
• Cough (50%)
• Haemoptysis (on at least one occasion is frequent but rarely
persistent)
• Chest pain (usually a diffuse chest wall heaviness)
• Upper limb pain/numbness (brachial plexus invasion)
• SOB (is the consequence of loss of lung volume from
consolidation distal to an occluded bronchus)
• Hoarseness (involvement of a recurrent laryngeal nerve)
• Dysphagia (oesophageal involvement)
• General features of malignancy:
o Weight loss
o Malaise
o Fatigue
Signs:
• General:
o Clubbing (30%)
o Hypertrophic pulmonary osteoarthropathy (3%) – with
painful swelling of the wrists and ankles
o Raised JVP and distended veins over the upper arms and
chest (with SVC obstruction)
• Signs of metastases are:
o Tender areas in bones
o Palpable supraclavicular lymph nodes
o An enlarged, irregular liver
o Anaemia
Investigations:
• CXR:
o Defines the lobar position of any mass
o May show:
• Pleural effusions
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• Elevation of the hemidiaphragm (indication of
phrenic nerve involvement)
• Rib erosion
• Thoracic CT or MRI:
o Excellent for accurate localisation
o In particular, CT defines:
• Additional small lung lesions
• Involvement of the pericardium, diaphragm, chest
wall and oesophagus (all of which may indicate
inoperability)
• Enlarged mediastinal glands (suggests malignant
involvement if >1cm)
• The anatomy of the liver and adrenals (both are
frequent sites of secondary spread)
• Mediastinoscopy:
o The aim is to obtain tissue from the mediastinal lymph
nodes around the lower trachea
o Is the most important staging procedure for inoperability
(N2 disease)
• Bone scan:
o Ca bronchus frequently metastasizes to bone
o Should be carried out if there is any clinical suggestion of
bone involvement:
• Bone pain
• Tenderness over the spine and other bony areas
• Raised ALP or serum calcium
o Multiple bone secondaries are an absolute contraindication
to surgery
• Liver ultrasound
• Brian isotope scan:
o Is indicated if neurological abnormalities are found:
• Severe persistent headache
• Syncope
• Ataxia or falls
• Stroke
• Behavioural change
Factors associated with inoperability:
• Oat cell carcinoma
• Poor respiratory function
• Evidence of lymphatic spread
• Presence of malignant cells in pleural effusion or heavy blood-
stained effusions
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• Evidence of distant spread:
o Bone
o Brain
o Liver
o Adrenals
Surgery:
• Thoracotomy and lung resection are performed whenever the
tumour is assessed as operable
• Early ligation of the pulmonary vein may help to prevent
metastatic spread from tumour manipulation
• Surgical mortality depends on patient-related risk factors and
the extent of the resection; with pneumonectomy average
mortality is 6-12% and for lobectomy 3-6%
• Specific risk factors are:
o Age
o Extent of resection
o Chronic lung disease
o Coronary artery disease/previous MI
o Concomitant disease of the:
• Liver
• Kidney
• Diabetes
Prognosis – squamous cell carcinoma:
• 5 year survival of primary lung cancers treated by surgical
resection is ~45%
• Survival depends on:
o Histological type; squamous cell tumours do better than:
• Adenocarcinoma
• Undifferentiated tumours
• Small cell tumours
o Tumour size (stages T1-T4)
o Lymph node spread (stages N0-N3)
Simplified TNM classification 5 year survival is shown below:
• T1 & N0 50-60%
• T2 & N1 30-55%
• T3 & N2 10-25%
• T4 & N3 0-2%
Prognosis – small cell (oat cell) carcinoma:
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• The outcome is particularly poor with resection alone (<5%
survival at 5 years)
• Chemotherapy is now the preferred method of treatment and
trials have shown an improved life expectancy, although still
very poor
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Carcinoma of the prostate
Prostatic carcinoma is a disease of ageing. It is rarely discovered under
the age of 50 and has a peak incidence in the 70s. It is rapidly
becoming the most common malignancy to affect men.
Pathological features:
• The tumour is an adenocarcinoma usually arising in the
periphery of the prostate and confined within the Prostatic
capsule
• Its spread is:
o Local in the periprostatic and perirectal soft tissues and
upwards into the pelvis
o Lymphatic to the iliac and para-aortic nodes
o Blood-borne, principally to bone
Symptoms:
• Bladder outflow obstruction
• Metastatic disease:
o Bone pain
o Leg swelling form lymphatic obstruction
• Renal failure from bilateral ureteric obstruction
Signs:
• A nodule in a palpably benign gland
• Hard, irregular prostate in rectal examination sometimes with
perirectal and periprostatic thickening
• Ankle/leg oedema
• Other signs of metastases
Investigation:
• A histological/cytological diagnosis must be made and can be
achieved by:
o Transrectal or transperineal biopsy, preferably US guided
o Aspiration cytology
o Transurethral resection
• Serum prostate-specific antigen (PSA):
o PSA is secreted in the serum by both benign and malignant
prostatic tissue
o Its level correlates with the volume of prostatic tissue
o Not useful for screening but is useful for monitoring the
progression of the disease and response to treatment
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• Abdominal ultrasonography:
o May identify unilateral or bilateral hydronephrosis because
of ureteric involvement
• Renal function tests
• Serum ALP:
o Will be elevated in patients with bony metastases
• Bone scanning:
o Radioisotope bone scans can detect areas of increased
bone activity, irrespective of their cause
Staging:
T1a Incidental finding of tumour with low biological potential for
aggressive behaviour in a prostate removed for clinically benign
disease
T1b Incidental finding of tumour with potentially biological aggressive
behaviour in a prostate removed for clinically benign disease
T1c Tumour identified because of elevated serum PSA
T2a Tumour involving half a lobe or less
T2b More than half a lobe but not both
T2c Both lobes
T3 Tumour extends through capsule and may involve seminal
vesicle
T4 Tumour fixed to invasive adjacent structures other than seminal
vesicle
Management options:
• No treatment with assessment of progress
• Endocrine therapy
• Radiotherapy
• Surgery
Endocrine therapy:
• Most of the proliferating cells of the prostate are dependent on
testosterone
• 60-80% of patients with symptomatic prostate cancer respond to
androgen suppression or ablation therapy
• The mean duration of response is 2 years
• Once the tumour is no longer hormone-sensitive, the mean
survival is 6 months
• Androgen suppression:
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o LHRH analogues initially stimulate the pituitary but after
~7 days the pituitary receptors become blocked and down-
regulation occurs
o Serum testosterone levels fall to castrate levels
o These drugs are long-acting and are administered sc every
1 or 3 months
o Due to the initial stimulation of the pituitary, an anti-
androgen should be given for 7-14 days before the LHRH
analogue is given to prevent disease progression
• Androgen ablation:
o Is by bilateral subcapsular orchidectomy, which can be
done under local anaesthesia as an outpatient
o There is no difference in response between orchidectomy
and LHRH analogue therapy and the choice of treatment
should lie with the patient
Radiotherapy:
• Is effective in controlling the pain of bony metastases
• It is also useful for the treatment of the primary if it is thought
that the tumour is confined to the prostate
Surgical treatment:
• Transurethral resection:
o Is used in patients who present with symptoms of outflow
obstruction or acute retention
• Radical prostatectomy:
o Controversial
o Only useful if the tumour is entirely confined to the
prostate
o Mortality of ~1%
• Morbidity includes:
o Incontinence
o Erectile dysfunction
o Anastomotic strictures
Prognosis:
• In men with prostate cancer confined within the capsule who
undergo radical prostatectomy, approximately 55% survive 10
years
• In comparison with those who have metastatic disease at
presentation, of whom only 25% can be expected to survive 5
years
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Chemotherapy
Overview:
• IV administration of anticancer agents enables therapy to
potentially reach metastatic disease in any part of the body
• However, the toxicity of chemotherapy determines that the
drugs can only be given intermittently and that time has to be
allowed for normal tissues to recover between each
administration of new cytotoxic drugs
• It is also known that tumours rapidly develop resistance to single
agents given on their own
• For this reason, the principle of intermittent combination
chemotherapy has developed:
o Several drugs are combined together
o Chosen on the basis of their differing mechanisms of action
and non-overlapping toxicities
• It has become apparent that normal tissue repairs much more
rapidly than cancerous tissue. This makes it possible to
continually deplete the tumour whilst allowing the restoration of
normal tissues between chemotherapy cycles
Side-effects of chemotherapeutic drugs:
• Nausea and vomiting
• Hair loss
• Bone marrow suppression
• Cardiotoxicity
• Neurotoxicity
• Nephrotoxicity
• Sterility
• Secondary malignancies
Drug resistance:
• This is one of the major obstacles to curing cancer with
chemotherapy
• Some tumours have an intolerably low-level of resistance to
currently available treatment and are often cured:
o Testicular teratomas
o HD
o Childhood acute leukaemia
• Solid tumours (such as small-cell lung cancer) initially appear to
be chemosensitive, with the majority of patients responding, but
most patients eventually relapse with resistant disease
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• In other tumours (e.g. melanoma) the disease is largely
chemoresistant from the start
Adjuvant therapy:
• When a patient first presents with a tumour, it is possible that
small amounts of tumour tissue have already spread to the
lungs, liver, bone marrow and other sites
• This micrometastatic disease consists of relatively few cells with
a good blood supply and might be particularly amenable to the
action of anticancer drugs
• Therefore, if the primary tumour is removed and the tumour has
a great likelihood of relapse, chemotherapy can be given to
destroy the residual micrometastatic disease
• Adjuvant therapy is very useful in childhood cancers
• In adults, adjuvant therapy has been shown to be of use in
breast and colon cancer
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Chronic lymphocytic leukaemia (CLL)
Overview:
• Is an incurable disease of older people
• Is characterised by an uncontrolled proliferation and
accumulation of mature B-cells (although T-cell CLL does occur)
• A proportion of patients remain asymptomatic, dying of an
unrelated cause
• In the remainder, the disease can usually be kept under control
for 9-10 years, infection being the predominant cause of death
Clinical features:
In asymptomatic patients, the diagnosis is often a chance finding on
the basis of a blood count done for a quite different reason
• Symptoms:
o Recurrent infections (resulting from neutropenia and
reduced Ig levels)
o Symptoms of anaemia:
• May develop rapidly in the context of haemolysis
(usually precipitated by infection)
o Painless lymph node enlargement
• Signs:
o Signs of anaemia
o Lymph node enlargement
o Enlarged liver and/or spleen
Investigations:
• FBC:
o Hb low or normal
o Raised WCC (of which at least 40% are lymphocytes)
o Platelets low or normal
• Serum Igs:
o Low or normal
• Coomb’s test:
o Positive if haemolysis is occurring
Treatment:
• The disease may remain stable for several years
• There is no advantage in starting treatment before there is a
clinical indication:
o Anaemia
o Recurrent infections
o Bleeding
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o ‘Bulky’ lymphadenopathy
o Increasing Splenomegaly
• Chlorambucil is most often used, with or without Prednisolone
• Treatment is given intermittently, as and when necessary
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Chronic myeloid leukaemia (CML)
Overview:
• The majority of patients with this disease are older and die
within 5 years of diagnosis
• Has a chronic phase (of 3-4 years duration) and an acute (or
blastic) phase
• The blastic phase of CML is characterised by the development of
acute leukaemia which may be:
o Myeloid (60%)
o Lymphoid (30%)
o Erythroid (10%), in origin
• The blastic phase is generally refractory to treatment, the
median survival being <6 months
Clinical features:
• Symptoms:
o Anaemia
o Night sweats
o Fever
o Weight loss
o Abdominal discomfort owing to splenic enlargement
• Signs:
o Those of anaemia
o Splenomegaly
Investigations:
• FBC:
o Hb normal or low
o Raised WCC (characteristically with the whole spectrum of
myeloid precursors)
o Platelets normal, low or raised
o Shows a hypercellular marrow with an increase in myeloid
precursors
o The Philadelphia (Ph) chromosome is present in most
patients
Treatment:
• Interferon (IFN) therapy:
o Induces haematological remission in most patients
o Induces cytogenetic remission in ~10% of patients
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o Problems:
• Has to be given subcutaneously
• Side-effects can be intolerable (mainly fatigue)
• Myeloablative therapy supported by allogeneic BMT:
o May be curative
o Limited by donor availability and the morbidity/mortality
associated with the treatment itself
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Hairy cell leukaemia (HCL)
Overview:
• HCL is a clonal proliferation of abnormal B (or very rarely T) cells
which, as in CLL, accumulate in the bone marrow and spleen
• Is a rare disease of late middle age
• The bizarre name relates to the appearance of the cells on a
blood film:
o They have an irregular outline owing to the presence of
filament-like cytoplasmic projections
Clinical features:
• Symptoms:
o Those of anaemia
o Recurrent infections
o Abdominal discomfort owing to splenic enlargement
• Signs:
o Those of anaemia
o A palpable spleen
Investigations:
• FBC:
o Pancytopenia
o Shows increased cellularity with characteristic infiltration
by ‘hairy’ cells
Treatment:
• 2-chloroadenosine (2-CDA) has been shown to have specific
activity in this illness, complete remission often being achieved
with just 1 cycle of treatment
• The remissions sometimes last for several years and patients can
be re-treated
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Hodgkin’s disease (HD)
Overview:
• Is one of 2 groups of lymphoma (HD and non-Hodgkin’s
lymphoma)
• Represents abnormal proliferation of B or T cells
• Is now curable in the majority of patients
• All stages are subclassified as A (asymptomatic) or B
Clinical features:
• Symptoms:
o Lymph node enlargement (most often of the cervical
nodes)
o ‘B’ symptoms:
• Fever
• Drenching night sweats
• Weight loss of >10% of bodyweight
o Other constitutional symptoms:
• Pruritus
• Fatigue
• Anorexia
• Alcohol-induced pain at the site of enlarged lymph
nodes
• Symptoms due to involvement of other organs (e.g. bone, lungs,
liver)
• Signs:
o Peripheral lymph node enlargement
o Hepatosplenomegaly
Differential diagnosis of cervical lymph node enlargement:
• Acute infections
• Chronic infections:
o TB
o Sarcoidosis
o Syphilis
o HIV
• Connective tissue disorders:
o RA
• Drugs:
o Phenytoin
• Primary lymph node malignancies:
o HD
o NHL
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o CLL
o ALL
• Secondary malignancies:
o Nasopharyngeal
o Thyroid
o Lung
o Breast
o Stomach
Investigations:
• FBC:
o May be a normocytic normochromic anaemia
• ESR:
o Usually raised
• LFTs:
o Abnormal if the liver is involved
• CXR:
o May show mediastinal widening, with or without lung
involvement
• CT scans:
o May show involvement of intrathoracic, abdominal or pelvic
lymph nodes
o May show involvement in patients with advanced disease
• Lymph node biopsy:
o Is required for definitive diagnosis
o Classically, Sternberg-Reed cells are present
Treatment:
• Treatment is nearly always given with curative intent
• Consists of chemotherapy, radiotherapy or both
• Treatment for HD can usually be given on an outpatient basis
and most people are able to lead a reasonably normal life whilst
having treatment
Prognosis at recurrence:
• Failure to achieve an initial or almost complete response, and
recurrence within 1 year, are both associated with a very poor
prognosis
• Similarly, patients who develop recurrent HD more than once will
almost certainly die of HD
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Myeloablative therapy with haemopoietic progenitor cell
support (HPCS)
Overview:
• High-doses of chemotherapy and radiotherapy kill dividing cells
indiscriminately, so that both normal and malignant cells are
killed
• Since the bone marrow is a highly dividing tissue,
myelosuppression is the main dose-limiting toxicity
• Thus, without a ‘transplant’ as a source of haemopoietic
progenitor cells, the person would die of bone marrow failure
• High-dose treatment may be given using one of the following as
a source of haemopoietic progenitor cells:
o Allogeneic bone marrow transplantation (BMT)/peripheral
blood progenitor cells (PBPCs)
o Autologous BMT/PBPCs
High-dose treatment with allogeneic BMT/PBPCs:
• The recipient patient first undergoes a ‘conditioning’ regimen of
myeloablative therapy over several days, comprising:
o Drugs
o Drugs + total body irradiation (TBI)
• The donor (usually an HLA-identical sibling) has ~1L of bone
marrow aspirated from the posterior iliac crests
• The BM is given IV to the recipient on completion of the
myeloablative therapy
• Immunosuppressive drugs (usually methotrexate and
cyclosporine A) are used to prevent both:
o Rejection
o Graft-versus-host disease (GVHD)
• The patient’ s blood count usually recovers within 3-4 weeks
• Can be very effective but has a 20-30% mortality
• The main causes of death are:
o Infection (bacterial, viral and fungal)
o GVHD
Graft-versus-host disease (GVHD):
• Is a syndrome in which mature T-cells in the donor BM infiltrate
the skin, gut and liver
• Acute GVHD occurs in the first 3 months, but it may also run a
chronic course
• When fatal, patients usually die of liver failure
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• Patients who develop GVHD have a lower incidence of recurrent
leukaemia than those who do not
• Thus, not only does the myeloablative chemoradiotherapy have
an anti-leukaemic effect, but the T-cells within the donor BM
appear to exert an immunologically-mediated ‘graft-versus-
leukaemia’ effect
• The use of allogeneic BMT is primarily limited by donor
availability
• Allogeneic PBPCs are currently being evaluated:
o Granulocyte-colony stimulating factor (G-CSF) is given to
the donor and haemopoietic progenitor cells are collected
from a vein
o Large volumes of blood are phoresed (centrifuged)
o The PBPCs are separated and collected and the RBCs,
granulocytes, platelets and plasma are then returned to
the donor through another vein
• Advantages include:
o Donor does not require a GA
o Donor does not have the discomfort associated with
collecting BM from the pelvic bones
o Incidence and severity of GVHD seems to be lower
High-dose treatment with Autologous BMT:
• Remission is first induced with chemotherapy
• 1L of BM is then aspirated from the patient’s posterior iliac crests
under GA and cryopreserved in liquid nitrogen
• The myeloablative therapy is then given and then thawed BM is
reinfused IV
• Advantages:
o Mortality is less than for allografts (5-10% compared with
20-30%)
• Disadvantages:
o The time to blood count recovery after an autograft is
usually longer than after an allograft
o Risk of reinfusing malignant cells (risk can be reduced
using in vitro techniques)
High-does treatment with autologous PBPCs:
• PBPCs have virtually replaced autologous BMT as support for
myeloablative therapy
• Chemotherapy followed by the growth factor G-CSF alone are
administered to stimulate haemopoietic progenitor cells in the
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BM to proliferate, so that they can be collected from the
peripheral blood
• Because PBPCs are more differentiated than those collected
directly form the BM, the time to blood count recovery is faster
(only 2-3 weeks)
• As the duration of neutropenia is shorter, the treatment is also
safer
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Myeloma
Overview:
• Is part of a spectrum of diseases
• Characterised by the presence of a paraprotein in the serum:
o Is produced by abnormal, proliferating plasma cells that
produce (most often) IgG or IgA (and rarely IgD)
• The paraproteinaemia may be associated with the excretion of
light chains in the urine (known as Bence-Jones protein)
Clinical features:
• Is a disease of the elderly (median age at presentation being 60
years)
• It is a complex illness which represents the inter-relationship
between:
o Bone destruction:
• Vertebral collapse (which can cause spinal cord
compression)
• Fractures
• Hypercalcaemia
o Bone marrow infiltration:
• Pancytopenia
• Production of paraprotein which may (rarely) result
in symptoms of hyperviscosity
o Renal impairment owing to a combination of:
• Deposition of light chains
• Hypercalcaemia
• Hyperuricaemia
Symptoms:
• Bone pain
• Symptoms of anaemia
• Recurrent infections
• Symptoms of renal failure (e.g. pruritus, anorexia, lethargy)
• Symptoms of hypercalcaemia
Investigations:
• FBC:
o All values are normal or low
• ESR:
o Raised
• Blood film:
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o May be rouleaux formation as a consequence of the
paraprotein
• U&Es:
o May be evidence of renal failure
• Serum Ca2+
:
o Normal or raised
• Serum ALP:
o Usually normal
• Total protein:
o Normal or raised
• Serum albumin:
o Normal or low
• Protein electrophoresis:
o Characteristically shows a monoclonal band (paraprotein)
• Uric acid:
o Normal or raised
• Skeletal survey:
o May show characteristic lytic lesions, most easily seen in
the skull
• Skeletal survey:
o To assess light-chain excretion
o Shows characteristic infiltration by plasma cells
General treatment:
• Anaemia corrected
• Infection treated
• Bone pain can be helped most quickly by radiotherapy
• Pathological fractures can be prevented by prompt orthopaedic
surgery with pinning of lytic bone lesions seen on the skeletal
survey
• Renal failure needs to be assessed and may need long-term
dialysis
• Patients with spinal cord compression due to Myeloma are
treated with dexamethasone, followed by radiotherapy to the
lesion delineated by an MRI scan
Specific treatment:
• The use of alkylating agents (e.g. melphalan, cyclophosphamide)
in conjunction with prednisolone has improved the median
survival from 7 months to 2 years
Prognosis:
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• Patients presenting with anaemia and renal failure have a very
poor prognosis, with 50% dying within 9 months
• Patients without these 2 features at presentation survive for
about 2 years
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Non-Hodgkin’s lymphoma (NHL)
Classification:
• The Kiel classification (reflects the rate at which the cells are
dividing):
o High-grade
o Low-grade
• Ironically, high-grade lymphomas are potentially curable,
whereas low-grade lymphomas are generally considered to be
incurable with conventional therapy
• A further subdivision is made in the basis of B- or T-cell origin:
o Most NHLs are of B-cell phenotype (although T-cell
tumours are increasingly being recognised)
Clinical features:
• Peripheral lymph node enlargement
• With or without systemic symptoms
Low-grade High-grade
Middle-aged/older people Any age group
Bone marrow infiltration common Bone marrow
infiltration unusual
Incurable with conventional therapy Potentially curable
Investigations:
• FBC:
o Pancytopenia (suggests bone marrow infiltration)
• U&Es:
o Patients may have renal impairment as a consequence of
ureteric obstruction secondary to intra-abdominal or pelvic
lymph node enlargement
• CXR
• LFTs
• CT scans
• Bone marrow aspirate
• Lymph node biopsy
Low-grade lymphomas:
• Are 4 subtypes:
o Follicular lymphoma (median survival is 9 years)
o Lymphoplasmacytoid (LPC) lymphoma (median survival is
5 years)
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