Concise Notes in Oncology 2005

Concise Notes in
Oncology for
MRCP and MRCS
Third Edition
Kefah Mokbel MB, BS (Lon), FRCS (Eng), MS (Lon),

FRCS (Gen)
Consultant Surgeon with a Specialist Interest in Breast
and Endocrine Surgery, St George’s Hospital, London
Professor at Brunel Institute of Cancer Genetics and
Pharmacogenomics (UK)
Radcliffe Publishing
Oxford . Seattle
CRC Press
Taylor & Francis Group
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© 2005 by Kefah Mokbel

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Contents
Preface to the third edition vi

About the author vii
List of abbreviations viii
Principles of cancer screening 1

Statistics 3
Drug pharmacology and clinical trials 6
1 Oncogenesis 8
2 Tumour growth and metastases 11
3 Principles of chemotherapy 14
4 Principles of radiotherapy 18
5 Cancer of the lip 20
6 Oral cancer 21
7 Cancer of the salivary glands 24
8 Retinoblastoma 26
9 Laryngeal cancer 28
10 Lung cancer 31
11 Breast cancer 35
12 Oesophageal cancer 44
13 Gastric cancer 48
14 Gastrointestinal lymphoma (GIL) 51
15 Small bowel carcinoma 54
16 Colorectal carcinoma 56
17 Anal cancer 61
18 Gall bladder cancer 63
19 Cholangiocarcinoma 66
20 Hepatocellular carcinoma (HCC) 69
iii
iv Contents
21 Carcinoma of the pancreas 72

22 Multiple endocrine neoplasia (MEN) syndromes 76
23 Insulinoma 77
24 Gastrinoma 79
25 Malignant phaeochromocytoma 80
26 Adrenocortical malignancy 82
27 Carcinoid tumours 84
28 Thyroid cancer 86
29 Parathyroid carcinoma 90
30 Soft tissue sarcoma (STS) 92
31 Kaposi’s sarcoma 96
32 Osteosarcoma 98
33 Cutaneous melanoma 100
34 Non-melanocytic skin cancer 104
35 Ovarian cancer 106
36 Endometrial carcinoma 109
37 Cervical cancer 112
38 Vaginal cancer 116
39 Vulval cancer 119
40 Renal adenocarcinoma 121
41 Wilms’ tumour 123
42 Urothelial carcinoma 125
43 Prostatic adenocarcinoma 128
44 Testicular cancer 131
45 Squamous-cell carcinoma of the penis 134
46 Primary intracranial tumours 136
47 Cerebral metastases 139
48 Spinal metastases 141
49 Acute leukaemia 144
50 Chronic leukaemia 149
51 Hodgkin’s lymphoma 152
52 Non-Hodgkin’s lymphoma (NHL) 156
Contents v
53 Multiple myeloma 159

54 Miscellaneous 162
55 Long-term venous access 167
56 Pain control in advanced cancer 170
57 Symptom control in advanced cancer 172
Preface to the
third edition
This book has two objectives. It is intended to provide an accurate,

concise source of information on medical and surgical oncology
and to serve as a platform on which to build new information
generated by the multitude of scientific and clinical disciplines that
continuously contribute to improving our understanding of cancer
and its management.
Each cancer is presented in an organised format that includes
information about epidemiology, aetiology, pathology, clinical
features, investigations, treatment and prognosis.
However, the approach adopted in this book is limited by the
amount of detail that can be provided, and it makes no allowances
for controversial opinions.
This publication will be valuable to undergraduate medical
students preparing for final examinations, postgraduate doctors
preparing for the MRCP and MRCS examinations, general prac-
titioners, oncology nurses and basic science researchers in the field
of oncology. It will also serve as a quick reference guide for medical
and surgical oncologists.
I have made every effort to ensure that the information contained
in this book is accurate at the time of going to press.
Kefah Mokbel
May 2005
vi
About the author
Professor Kefah Mokbel is Consultant Breast and Endocrine Sur-

geon to St George’s Hospital and a Professor at the Brunel Institute
of Cancer Genetics and Pharmacogenomics. His main clinical inter-
ests include breast cancer surgery, including breast reconstruction
and sentinel node biopsy, cosmetic breast surgery, including breast
enlargement, breast reduction and mastopexy (breast lift). His
main academic interests lie in the field of postgraduate education
and research into molecular biology and the clinical management
of breast cancer. He has had over 120 papers published in the
medical literature and has written 10 books for postgraduate edu-
cation. He is a member of the editorial board of several inter-
national medical journals. He also has an active research and
teaching programme at St George’s Hospital and Medical School,
Brunel University (Institute of Cancer Genetics and Pharmaco-
genomics) and Kingston University (Life Sciences). He also super-
vises undergraduates and postgraduate research degrees. Professor
Mokbel lectures nationally and internationally and teaches tech-
niques of modern breast surgery, including skin-sparing mastec-
tomy and immediate breast reconstruction, mammary ductoscopy
and sentinel node biopsy.
vii
List of
abbreviations
ACTH adrenocorticotrophic hormone

ADH antidiuretic hormone
AFP a-fetoprotein
AIDS acquired immunodeficiency syndrome
ALL acute lymphoblastic leukaemia
AML acute myeloid leukaemia
BCC basal-cell carcinoma
BCS breast-conserving surgery
BMT bone-marrow transplantation
BPH benign prostatic hyperplasia
CBD common bile duct
CEA carcino-embryonic antigen
CIN cervical intra-epithelial neoplasia
CIS carcinoma in situ
CLL chronic lymphocytic leukaemia
CML chronic myelocytic leukaemia
CNS central nervous system
CSF cerebrospinal fluid
CT computed tomography
CXR chest X-ray
DCIS ductal carcinoma in situ
DVT deep vein thrombosis
EBV Epstein–Barr virus
ECM extracellular matrix
EEG electroencephalogram
EGFR epidermal growth factor receptor
ER oestrogen receptor
ERCP endoscopic retrograde cholangiopancreatography
ESR erythrocyte sedimentation rate
EUA examination under anaesthetic
viii
List of abbreviations ix
FBC full blood count/familial breast cancer

FIGO International Federation of Gynaecology and Obstetrics
FISH fluorescent in situ hybridisation
FNAC fine-needle aspiration cytology
5-FU 5-fluorouracil
GI gastrointestinal
Gy gray
HBV hepatitis B virus
HCC hepatocellular carcinoma
HIV human immunodeficiency virus
HPV human papilloma virus
HSV herpes simplex virus
IHC immunohistochemistry
IM intramuscularly
IV intravenously
IVP intravenous pyelography
IVU intravenous urogram
KS Kaposi’s sarcoma
LABC locally advanced breast cancer
LFT liver function test
MBC metastatic breast cancer
MEN multiple endocrine neoplasia
MRI magnetic resonance imaging
MTC medullary thyroid carcinoma
MTH medullary thyroid hyperplasia
NSCLC non-small-cell lung cancer
OCP oral contraceptive pill
PET positron emission tomography
PSA prostate-specific antigen
PTC percutaneous transhepatic cholangiogram
PTH parathyroid hormone
PUVA psoralen with ultraviolet radiation A (long-wave)
RT radiotherapy
SCC squamous-cell carcinoma
SCLC small-cell lung cancer
SNB sentinel-node biopsy
TCC transitional-cell carcinoma
TNM tumour/node/metastasis staging
x List of abbreviations
TSG tumour suppressor gene

TSH thyroid-stimulating hormone
TURP transurethral resection of the prostate
U&Es urea and electrolytes
USS ultrasound scan
UV ultraviolet
VMA vanillyl mandelic acid
WBC white blood count
5-HT 5-hydroxytryptophan
Principles of
cancer screening
Basic principles
. Screening may allow the detection of early disease in the
asymptomatic population.
. The objective of screening, namely to reduce morbidity and
mortality in those screened, must be balanced against the
effectiveness of the programme.
. Screening may be applied to mass populations or to high-risk
groups.
Reliability of a screening test

. Sensitivity of the test is the proportion of individuals with the
cancer who test positive. Sensitivity is a measure of false-
negative results.
. Specificity of the test is the proportion of individuals without
cancer who test negative. Specificity is a measure of false-
positive results.
. Positive predictive value is the proportion of individuals with a
positive test who have a diagnosis of cancer.
. Negative predictive value is the proportion of individuals with
a negative test who do not have cancer.
1
2 Concise notes in oncology for MRCP and MRCS
Biases within a screening programme

. Selection bias occurs when those attending for screening may
have a better prognosis than, and are different from, the normal
general population.
. Lead-time bias occurs when an earlier diagnosis is made by the
screening test but the natural history is unaffected.
. Length bias occurs when patients with cancers are identified
because they have slowly growing cancers leading to better
survival.
Attributes of a screening programme

. Ethically, the benefits of the programme should outweigh the
risks associated with taking part in the programme.
. The cancer under study must have a long pre-clinical phase and
the natural history should be well determined.
. Is there evidence from randomised controlled trials that treat-
ment is effective?
. Does early treatment make a difference to outcome?
. Is the screening test reliable, acceptable to the population and
economically viable?
. Is the morbidity associated with the screening test acceptable?
Statistics
. The median value of a set of data is the central observation after

the values have been ranked in order of size. That is, half of the
data will have a value less than the median, and the other half of
the data will have a value greater than the median. When the
median is used as an indication of the central point of some
data, then the centiles (e.g. quartiles, 95th centile, etc.) should
be used as an indication of the shape or spread of the data.
. The mean is the sum of all the values in the population divided
by the number of values in the population. When the mean is
used as an indication of the central point of some data, then the
standard deviation should be used as an indication of the shape
or spread of the data.
. The null hypothesis (H0) states that there is no difference
between the data sets being compared and any apparent dif-
ference is due to chance.
. The P-value indicates the probability that the null hypothesis is
correct. Therefore if it is a small value (e.g. < 0.05), the null
hypothesis is rejected and the test is considered to be statistic-
ally significant (i.e. any difference that is observed is unlikely to
be due to chance).
. A confidence interval gives an estimated range of values which
is likely to include an unknown population parameter. The
confidence level that is usually chosen for analysis is 95%.
Confidence intervals are more informative than the simple
results of hypothesis tests.
. In a normal distribution (which is symmetrical and bell-shaped),
the mean and median are identical. A similar symmetrical, bell-
shaped distribution is called the t distribution with (n–1)
degrees of freedom. The t distribution also has a mean of 0,
but the tails of the distribution are more spread out. The exact
shape of the t distribution depends on what are called degrees
of freedom (df). The df are equal to the sample size minus 1.
3
Parametric tests such as the two-sample t-test and the paired

t-test can be used with this type of data.
. Analysis of variance (ANOVA) is the term given to the method
of analysing data from two or more groups.
. When the data are clearly not normally distributed, an alterna-
tive method is to use non-parametric techniques. These include
the Mann–Whitney U-test and the Wilcoxon matched pairs
test.
. The chi-squared test is a non-parametric test that is commonly
used to assess frequency data and goodness of fit. It is prefer-
able to use Fisher’s exact test for 2 2 contingency table
analysis instead of the chi-squared test.
. Correlation and regression methods examine the relationship
between two continuous variables. Pearson’s correlation coef-
ficient (r) is a measure of the strength of the linear relationship
between two parametric variables. A major assumption is the
normal distribution of variables. If this is not met, the non-
parametric equivalent, Spearman’s rank correlation, should be
used. The correlation coefficient r can take any value between
–1 and +1.
. The Cox regression method is used for modelling survival
times. It is also called the proportional hazards model because
it estimates the ratio of the risks (hazard ratio). As in any
regression model, there are multiple predictor variables, such
as prognostic parameters, whose individual contribution to the
outcome is being assessed in the presence of the other predictor
variables and the outcome variable. The model assumes that
the underlying hazard rate is a function of the independent
variables and that it is consistent over time.
. The survival curves are calculated using a procedure called the
Kaplan–Meier method. Mathematically removing a patient
from the curve at the end of their follow-up time is called
‘censoring’ the patient. Survival curves often have a tick mark
at each point where a patient was censored. To determine the
significance of the difference between survival times, the log
rank test is used.
. The odds ratio (OR) is the ratio of the odds of the risk factor in a
study group to those in a control group. The OR is used in
retrospective case–control studies, whereas the relative risk
Statistics 5
(RR) is the ratio of proportions in two groups which can be

estimated in a prospective cohort study. These two ratios and
the relative hazard ratio (or hazard ratio) are measures of the
strength/magnitude of an association.
. A meta-analysis integrates the quantitative findings from sep-
arate but similar studies and provides a numerical estimate of
the overall effect of interest.
. Absolute risk refers to the probability of an event occurring
over a period of time. It is expressed as a cumulative incidence.
It indicates the actual likelihood of an event occurring and
provides a more realistic and comprehensible risk than the
relative risk or odds ratio.
. A type I error is the kind of error that occurs if we reject the null
hypothesis when it is true. If the null hypothesis is accepted
when it is in fact wrong, this is a type II error. The statistical
power of a test is equal to 1 minus the type II error. It is desirable
for the power to exceed 80%.
. Survival statistics for cancer are usually expressed as 5-year
survival or 10-year survival. Disease-free survival figures refer
to everyone with that type of cancer who is alive and well
without cancer recurrence.
Drug pharmacology
and clinical trials
Basic principles
. Only 5–10% of all cancers are curable with currently available
therapies – hence the need for drug development.
. Pharmacokinetics refers to drug absorption, distribution,
metabolism and elimination. An understanding of pharmaco-
kinetics may allow optimisation of effective drug delivery and
hence of therapy.
. Pharmacodynamics is the study of the end-organ effects of the
drug, and includes both the toxicity of the drug and its thera-
peutic actions.
. The dose, dose rate and schedule of drug administration all
have a major influence on drug efficacy in oncology.
. A measure of drug exposure that is often used is the area under
the plasma concentration versus time curve (the AUC).
. Relationships between pharmacokinetic (e.g. AUC) and pharma-
codynamic (e.g. percentage change in platelet count) param-
eters have been described (e.g. for carboplatin), and can be used
prospectively to minimise toxicity and potentially maximise
activity.
Clinical trials
. The development of new drugs has been based on pre-clinical
in-vitro and in-vivo studies. This process has been accelerated
by the use of X-ray crystallography and the design of active
compounds based on the crystal structure of the target. Toxi-
cology data from pre-clinical in-vivo studies are used to derive
the starting dose for Phase I studies.
6
Drug pharmacology and clinical trials 7
. Phase I clinical trials focus on drug toxicity and dosing schedules.

Clinical pharmacokinetics are studied in detail, and pharma-
cokinetic analysis may be non-compartmental or compartmental,
based on mathematical modelling. The primary aim of these
studies is to determine the maximum tolerated dose (MTD) and
the dose recommended for Phase II studies. This is achieved
by means of dose escalations, which are determined through
observed toxicities and pharmacokinetic analysis and pharma-
codynamic studies relating drug toxicity to drug exposure
(AUC). Phase I studies usually involve patients who have failed
on previous treatment regimes, and usually small numbers of
patients are treated at each dose level, the total number of
patients involved in the trial tending to be around 30 on
average. Patients are selected on the basis of strict eligibility
criteria.
. Phase II trials use doses and schedules based on Phase I data.
The aim of these trials is usually to determine efficacy based
on tumour response. The studies select patients with specific
tumour types and each trial assesses response. The study design
may be based on fixed study subjects or on evaluations after
subjects have been entered.
. Phase III trials are full-scale evaluations of the drug, involving
randomisation, control groups, different study populations
and treatment protocols.
. Phase IV involves post-marketing surveillance.
1 Oncogenesis
Basic principles
. Carcinogenesis is a multi-step process.
. Initiation ! promotion ! cancer.
. Initiation is irreversible, whereas promotion is reversible.
. The effects of initiation are inheritable.
. DNA structural changes lead to tumour development.
Host factors in carcinogenesis

. Immune system.
. Endogenous hormones.
. Genetic factors such as oncogenes and tumour suppressor genes.
Environmental factors in carcinogenesis

. Radiation can cause DNA damage. It includes:
– ionising radiation (e.g. X- and U-rays, and a- and b-particles)
– non-ionising radiation (e.g. UV light).
. Chemical carcinogens. These include:
– polycyclic hydrocarbons
– aromatic amines
– alkylating agents
– blue asbestos
– aflatoxins (hepatocellular carcinoma)
– nicotine.
. Viruses. These include:
– Epstein–Barr virus (EBV). This is a DNA oncogenic virus. It
is a member of the herpes virus family. It is associated with
Burkitt’s lymphoma and nasopharyngeal carcinoma
8
Oncogenesis 9
– hepatitis B virus (HBV). The incidence of hepatocellular

carcinoma is increased by 200-fold in chronic carriers of HBV
– human papilloma virus (HPV). This virus is associated with
cervical cancer and epidermodysplasia verruciformis (mul-
tiple squamous-cell carcinomas of the skin)
– human T-cell leukaemia virus (HTLV-1). This is an RNA
virus. It is associated with several malignancies, including
leukaemias and lymphomas.
Mechanisms of cancer pathogenesis

These include the following.
. Oncogenes are cancer-promoting genes which are derived from
normal genes known as proto-oncogenes.
. Tumour suppressor genes restrict or repress cellular prolifer-
ation in normal cells. Their inactivation through somatic
mutation or germ-line incorporation is associated with renal,
colonic, breast, bladder and other cancers.
. DNA repair genes.
. Loss of imprinting.
Oncogenes
. These are genes associated with neoplastic proliferation. The
antecedent genes (known as proto-oncogenes) play an import-
ant physiological role in cellular growth.
. They can be classified into growth factors, growth factor
receptors (e.g. erbB and fms), protein kinases (e.g. abl, src,
mos and raf), signal transduction G proteins (e.g. H-, K- and
N-ras) and nuclear proteins (e.g. c-myc, n-myc, fos, myb and
jun).
. They are implicated in 20% of human tumours.
. Methods of activation include chromosomal rearrangement,
gene amplification, point mutations and viral insertion.
Tumour suppressor genes (TSGs)

. Loss or inactivation of TSGs can lead to neoplastic changes.
. p53 is a tumour suppressor gene located on chromosome
17p13.1. The normal form is known as the wild type. Loss of
heterozygosity can lead to malignancy.
. Other examples of TSG include RB1, BRCA-1, BRCA-2 and
DCC.
DNA repair genes

. There are two major pathways of DNA repair, namely mis-
match repair and nucleotide excision repair.
. Examples include xeroderma pigmentosa and the ataxia tel-
angiectasia gene. Mutation of the latter (ATM) predisposes to
leukaemia, lymphoma, and breast and skin cancers.
Loss of imprinting
. Imprinting refers to the fact that the parental origin of the gene
can affect its expression.
2 Tumour growth
and metastases
Tumour cells can successfully metastasise if they have the ability to:
. regulate the production of proteases (by the tumour cells or
surrounding stroma cells)
. regulate the production of adhesion molecules
. regulate the expression of major histocompatibility complex
(MHC) units and escape immune surveillance, including natu-
ral killer cells
. regulate the process of clotting
. respond to cytokines and growth factors.
The metalloproteinases
. There are at least eight members of this group of lytic enzymes
that are responsible for the degradation of the extracellular
matrix (ECM).
. They are secreted by the stromal elements or the tumour cells.
Cadherins
. These are transmembrane glycoproteins which mediate haemo-
philic adhesions between cells.
. Down-regulation of E-cadherins is associated with dediffer-
entiation and metastasis of cells.
11
Integrins
. These are transmembrane proteins which mediate cell ad-
hesion to the ECM proteins and transmit signals.
The sequential steps of metastasis

These include the following.
. Malignant transformation.
. Cell proliferation resulting in a primary tumour mass.
. Angiogenesis when primary tumour exceeds 2 mm in diameter.
. Detachment of cells from primary tumour in association with
down-regulation of E-cadherins.
. Detached tumour cells interact with ECM by integrins.
. Motility of tumour cells is stimulated by scatter factor secreted
by fibroblasts or by motility factors secreted by the tumour
cells.
. Metalloproteinases secreted by tumour cells or stromal fibro-
blasts degrade ECM and allow invasion of blood vessels and
lymphatics.
. Within blood vessels/lymphatics some tumour cells are at-
tacked by T-cells, while others escape immune surveillance
due to lack of or altered MHC units.
. Tumour cells adhere to endothelial cells via integrins, intra-
cellular adhesion molecules, selectins, CD44 and other ad-
hesion molecules.
. Tumour cell invasion of target tissues is facilitated by metallo-
proteinases which degrade ECM.
TNM classification
. Solid tumours can be staged according to the TNM system.
. The TNM staging system is a systematic method of describing
the size, location and spread of a tumour.
. T describes the primary tumour according to its size and
location (T0, T1, T2, etc.).
Tumour growth and metastases 13
. N indicates whether the cancer has spread to the regional

lymph nodes (i.e. N0 or N1).
. M indicates whether the cancer has spread to distant organs in
the body (M0 or M1).
. X indicates that the status is not known (e.g. MX means that we
do not know whether metastatic disease to other organs is
present).
. Group staging is frequently used to include several TNM stages
in one group (e.g. stage I can include T1N0M0, T2N0M0 and
T1N1M0 tumours).
Gene expression profiling

Gene expression profiling is a new microarray-based technology
that determines the expression of a large number of genes in tissue
specimens simultaneously. This analytical method is currently
being investigated as an emerging diagnostic and prognostic tool
for several human cancers. An important assumption behind this
research is that the constellation of multiple genes will be a more
accurate predictor of clinical outcome than any single gene alone.
These new technologies are more potent when coupled with ad-
vanced bioinformatics analysis.
Proteomics
Proteomics is the analysis of proteins present in the organism in
normal and pathological conditions using microarray-based tech-
nology, mass spectrometry and advanced bioinformatics analysis.
This allows scientists to identify the proteomic biosignatures of
human cancer in both serum and tissue specimens. The potential
clinical applications include diagnosis, tailoring of therapy, pre-
diction of outcome and the identification of new targets for therapy.
3 Principles of
chemotherapy
The cell cycle
G0 G1
Antimetabolites, e.g.
5-FU, methotrexate
M S
Spindle poisons,
e.g. vincristine,
paclitaxel
G2 Bleomycin
Figure 1 The cell cycle. M = mitosis phase, G1 = gap 1, S = synthesis

phase, G2 = gap 2, G0 = resting phase.
. The duration of the cell cycle is approximately 48 hours.

. Stimulatory signals come from cyclins (cyclins D and E in the
G1 phase, cyclin A in the S phase and cyclin B in the G2 and M
phases). Inhibitory signals come from tumour suppressor genes
(e.g. p53 and RB1).
. Cytotoxic drugs kill tumour cells and normal cells, but tumour
cells have a greater sensitivity to these drugs or a reduced ability
to repair cytotoxic damage.
. Chemotherapy agents can be cycle specific (e.g. alkylating and
intercalating) or phase specific (e.g. spindle poisons and
antimetabolites).
14
Principles of chemotherapy 15
Classification of cytotoxic drugs

. Alkylating agents:
– chemically react with the structure forming methyl cross-
bridges between the two strands of DNA base pairs. This
prevents the DNA strands from coming apart during mitosis,
and division therefore fails
– examples include nitrogen mustards, melphalan, chlorambucil,
cyclophosphamide, busulfan, nitrosoureas, platinum and
dacarbazine.
. Antimetabolites:
– inhibit the formation of essential nucleic acids, thus inter-
fering with DNA/RNA synthesis and causing cell death
– examples include methotrexate, 5-fluorouracil (5-FU), cytosine,
arabinoside and purine analogues
– folinic acid can be given to rescue cells from the effect of
methotrexate.
. Anti-tumour antibiotics:
– anthracyclines include doxorubicin, daunorubicin and epi-
rubicin. These drugs intercalate between base pairs of DNA,
causing DNA damage. Mitoxantrone is structurally related
to this group of drugs
– bleomycin – this drug is G2 specific
– mitomycin C – this acts as an alkylating agent and generates
free radicals capable of causing DNA damage
– actinomycin D – this intercalates between guanine and
cytosine, thus inhibiting DNA/RNA synthesis
– platinum analogues (cisplatin and carboplatin).
. Plant-derived cytotoxic drugs:
– vinca alkaloids. Vincristine, vinblastine and vindesine in-
hibit the formation of mitotic spindles by binding to tubulin
– epidophyllotoxins (e.g. etoposide). These drugs interfere with
topoisomerase II enzymes, causing DNA damage during the
S phase
– paclitaxel (Taxol) inhibits mitosis by promoting a disorgan-
ised and stabilised assembly of microtubules. It is a new drug
and is mainly used in the treatment of breast and ovarian
cancers. Docetaxel (Taxotere) is a similar drug.
. Other drugs:
– dacarbazine is an alkylating agent used in the treatment of
melanoma
– procarbazine is used to treat Hodgkin’s lymphoma.
Chemotherapy protocols
. Combinations are usually used.
. Pulsed or intermittent therapy is frequently used in order to
allow a larger dose to be given.
. High-dose chemotherapy can be given with the use of haema-
topoietic growth factors, stem cell support or autologous bone
marrow transplantation in order to counteract myelosuppression.
Mechanisms of drug resistance

. Increased concentrations of target enzymes (e.g. doxorubicin,
epirubicin, paclitaxel, vincristine).
. Reduced uptake by tumour cells (e.g. daunorubicin).
. Increased activity of salvage pathways (e.g. antimetabolites).
. Detoxification.
. Improved DNA repair mechanisms by target cells.
. Impairment of activation or increased inactivation of the drug.
Biological therapy
. Recent advances in molecular biology have led to the develop-
ment of numerous biological therapies.
. Herceptin is a recombinant humanised monoclonal antibody
that binds and blocks the growth receptor HER2. It has been
shown to be effective in patients with metastatic breast cancer
overexpressing HER2. Phase II trials are currently in progress in
patients with ovarian cancer.
. Rituximab is an anti-CD20 monoclonal antibody which seems
to be effective in the treatment of refractory indolent lymphoma
and hairy cell leukaemia.
Principles of chemotherapy 17
. Angiogenesis inhibitors include angiotensin, endostatin and

epidermal growth factor receptor (EGFR) antagonists. These
agents are currently being evaluated.
. Immunotherapy.
4 Principles of
radiotherapy
Basic principles
. X-rays are the commonest type of ionising radiation used in
clinical practice. They are produced artificially by accelerating
electrons (linear accelerators) using microwave energy, result-
ing in the production of therapeutic megavolt beams.
. Gamma rays are similar to X-rays but arise from the decay of
radioactive isotopes.
. Ionising radiation causes irreversible DNA damage either dir-
ectly or indirectly by generating toxic free radicals. The DNA
damage, which is oxygen dependent, is the most important
factor in cell killing.
. Radiotherapy dose is expressed in grays or centigrays (1 Gy =
100 cGy), and describes the energy absorbed per unit mass of
tissue.
. Fractionation allows a higher degree of radiation to be given.
Clinical applications
. Cancer patients are treated either by external beam radiation
(linear accelerator or cobalt machine) or by insertion of a
radioactive material into body tissues (interstitial radiotherapy)
or cavities (intracavity radiotherapy).
. Radiotherapy can be palliative or curative. It can be combined
with other treatment modalities such as surgery and chemo-
therapy. Pre-operative radiotherapy may be given in order to
render a tumour operable. Post-operative radiotherapy is used
mainly to reduce the rate of local recurrence.
18
Principles of radiotherapy 19
. The effects of radiotherapy depend on the dose, the tumour

size, the tumour proliferation rate, hypoxia, tumour radio-
sensitivity, the patient’s performance, the presence of anaemia
and vascular disease.
Side-effects
. Early side-effects include mucositis, alopecia, skin erythema,
nausea, vomiting, enteritis and bone marrow suppression.
These side-effects are reversible and can be managed sympto-
matically.
. Late side-effects include spinal cord myelitis, pneumonitis,
strictures, telangiectasia and secondary cancers. Approximately
3% of patients develop a second cancer 15 years after treat-
ment.
5 Cancer of the lip
Epidemiology
. The incidence is higher among Caucasians (compared with
blacks), smokers and outdoor workers.
. Cancer of the lip accounts for 25% of oral malignancies.
Pathology
. Smoking (especially pipe smoking) and solar radiation are
important aetiological factors.
. Squamous-cell carcinoma (SCC) is the commonest histological
type. Basal-cell carcinoma is occasionally seen.
. Around 92% of lesions occur on the lower lip, 5% occur on the
upper lip and 3% at the angle of the mouth.
. Submandibular nodes are the usual sites for metastases.
Investigation
. Limited surgical biopsy under local anaesthetic.
. Fine-needle aspiration cytology (FNAC) of enlarged lymph nodes.
Treatment
. Surgery and radiotherapy are equally effective.
. Surgical defects following adequate excision can be reconstructed
using local flaps (from the opposite lip) or closed primarily if
small. Local reconstruction aims to maximise the functional
and cosmetic outcomes.
. The cure rate is 90%.
20
6 Oral cancer
Epidemiology
. It accounts for 4% of all cancers (India has the highest incidence).
. Peak incidence is in the age group 50–70 years.
. It is more common in men.
. The tongue is the commonest site.
Pathology
. Squamous-cell carcinoma (SCC) accounts for 90% of all cases.
. Adenocarcinoma accounts for 3% of cases.
. Kaposi’s sarcoma, lymphoma and melanoma are rare.
. The TNM system is used for staging.
Aetiology
Risk factors include:
. smoking and chewing tobacco
. alcohol
. infections (syphilis, candidiasis and herpes virus)
. immunosuppression
. industrial hazards (textile workers, nickel exposure)
. oncogenes (ras, p53, L-myc and C-myc)
. leukoplakia
. erythroplakia.
Clinical presentation
. Ulcerating lesions.
21
. Exophytic lesions.
. Induration.
. Swelling.
. Pain.
. Pathological mandibular fractures.
. Paraesthesia along the inferior alveolar nerve distribution.
. Lymphadenopathy in the head and neck region.
Investigations
. Exfoliative cytology.
. Surgical biopsy including a margin of healthy tissue.
. CT and MRI.
. FNAC of enlarged lymph nodes.
. Plain radiograph of adjacent teeth may be useful.
Treatment
. SCC of the anterior two-thirds of the tongue.
– This can be treated with surgical excision (with a 1 mm
margin) or radiotherapy.
– Large surgical defects can be reconstructed using split-
thickness skin grafts, local skin flaps (forehead or delto-
pectoral), myocutaneous flaps (pectoralis major or trapezius)
or free flaps (microvascular anastomosis).
. SCC in the floor of the mouth.
– If the alveolar process is involved then wide local excision
with reconstruction (local or free flaps) is appropriate.
– If the alveolar process is not involved, then radiotherapy is
the treatment of choice.
. SCC on the mandibular alveolus is treated with surgical ex-
cision and reconstruction using bone grafting or a free flap
utilising the underlying bone (radial forearm flap).
. SCC of the buccal mucosa is treated with surgical resection and
the defect is reconstructed with a local or free flap.
Oral cancer 23
. SCC on the upper jaw is treated with surgical excision and

reconstruction using a prosthetic appliance lined with skin
graft if necessary.
. Supraomohyoid or modified radical neck dissection may be
necessary, depending on lymph node involvement.
. Post-operative adjuvant radiotherapy or chemotherapy may be
necessary.
Prognosis
. The overall 5-year survival rate of patients with carcinoma of
the tongue is approximately 40%. Posterior location and ad-
vanced stage are adverse prognostic parameters.
7 Cancer of the
salivary glands
Epidemiology
. The incidence is 1.5 per 100 000 per year.
. Around 70% of the lesions occur in the parotid gland (20% are
malignant).
Aetiology
. Malignant transformation of a pleomorphic adenoma.
. Radiation.
. Association with breast cancer.
Pathology
. The grade (high grade or low grade) is more important than the
histological type (acinic cell, mucoepidermoid or carcinoma) in
predicting behaviour and prognosis.
. Swelling (rate of growth depends upon grade of tumour).
. Facial nerve palsy (parotid tumours).
. Sensory loss in anterior two-thirds of the tongue (subman-
dibular tumours).
. Trismus and pain along the trigeminal nerve distribution.
. Lymphadenopathy (25% of cases).
24
Cancer of the salivary glands 25
Investigations
. Core biopsy or FNAC.
. Open biopsy.
. CT or MRI.
. Staging investigations include CXR, thoracic CT and bone
scan.
Management
. Surgical excision for low-grade tumours.
. Surgical excision followed by radiotherapy for high-grade
tumours.
. The facial nerve may be sacrificed in some cases.
. Neck dissection is indicated in the presence of lymph node
metastases (confirmed by FNAC).
. Pre-operative radiotherapy followed by surgery for locally
advanced tumours.
. Radiotherapy alone has a local control rate of 30% in patients
with locally advanced tumours.
. Plastic reconstruction may be performed using pectoralis
major, trapezius and latissimus dorsi myocutaneous flaps or
a radial forearm free flap.
Prognosis
. For low-grade tumours the 10-year survival rate is 90%.
. For high-grade tumours the 10-year survival rate is 25%.
. In addition to grade, histopathological subtype, tumour stage
and margin status significantly influence the prognosis.
8 Retinoblastoma
Epidemiology
. The incidence is 1 per 15 000 live births.
. It accounts for 3% of all childhood malignancies.
. The incidence is increasing. It has doubled in the last 40 years.
Aetiology
. Most cases are sporadic.
. Some cases are inherited in an autosomal dominant fashion.
Sporadic bilateral retinoblastoma and familial retinoblastoma
are inheritable.
. The retinoblastoma (Rb) gene is a growth suppressor gene. Its
product has a general suppressive function in the cell cycle.
Pathology
. The tumour usually consists of undifferentiated and small cells
with deeply staining nuclei and scanty cytoplasm.
. The tumour is usually multifocal.
. The commonest mode of metastasis is via the bloodstream to
bone marrow, liver, lungs and lymph nodes.
. The tumour is classified according to the Reese–Ellsworth
system into five groups (I–V).
Clinical features
. The tumour usually presents before the age of 2 years.
. ‘White pupil’ is the commonest presentation.
26
Retinoblastoma 27
. Other features include strabismus, glaucoma, defect in visual

fixation and inflammatory changes within the eye.
. Ophthalmological assessment is required in such cases. Sur-
gical biopsy is not recommended.
Investigations
. Full blood count (FBC), bone scan and CXR.
. Orbital CT or MRI.
. Analysis of CSF if intracranial spread is suspected.
Management
. Cryosurgery or photocoagulation for very small lesions.
. Brachytherapy (for lesions measuring 3–10 mm) using radio-
active cobalt.
. External beam radiation (35–40 Gy over 4 weeks) for large
lesions and for lesions near the optic disc and macula.
. Eye enucleation for tumours that are unresponsive to conser-
vative management and for tumour that is occupying most of
the eye and infiltrating the optic nerve. Post-operative radio-
therapy may be given in such cases.
. Chemotherapy may be used for extra-ocular disease and to
reduce the bulk of primary disease in order to allow conserva-
tive treatment (chemoreductive neoadjuvant therapy). Effec-
tive agents include vincristine, actinomycin D, doxorubicin,
methotrexate and cyclophosphamide.
. An orbital integrated implant can be placed after enucleation,
and provides acceptable prosthesis motility and appearance.
. Genetic counselling is an important part of management.
Prognosis
. The cure rate for stages I and II is 100%.
. The cure rate for stages IV and V is 75%.
. The overall mortality is 10%.
9 Laryngeal cancer
Epidemiology
. Laryngeal cancer accounts for 2–3% of all malignant disease.
. The male:female ratio is 10:1.
. The disease occurs exclusively in smokers.
. The peak age of onset is 60 years.
Pathology
. Squamous-cell carcinoma accounts for most cases.
. Adenoid cystic carcinoma and sarcoma are rare.
. Laryngeal cancer can be classified into four types according to
site of origin:
– glottic (60%)
– supraglottic (30%)
– subglottic (5%)
– marginal (5%).
. The disease spread is local initially.
. Lymphatic spread is to deep cervical lymph nodes.
. Pulmonary metastases are occasionally seen.
Clinical features
. Hoarseness is the main symptom of the disease.
. Other symptoms include:
– dysphagia
– earache
– dyspnoea
– haemoptysis.
28
Laryngeal cancer 29
Investigations
. Microlaryngoscopy and biopsy.
. CXR.
. CT to define the extent of the disease.
Treatment
. Glottic tumours.
– Carcinoma in situ can be treated by local excision of the
involved mucosa. This can be performed endoscopically.
– T1 and T2 lesions can be effectively treated with radio-
therapy. The resulting voice quality is better than after partial
(vertical) laryngectomy. Salvage surgery in the form of par-
tial or total laryngectomy is performed in cases where failure
occurs with radiotherapy treatment.
– Tumours involving the contralateral cord can be treated by
total laryngectomy. Post-operative radiotherapy may be given.
. Early supraglottic tumours are treated by pre-operative radio-
therapy and subsequent total laryngectomy.
. Advanced supraglottic, subglottic and glottic tumours are treated
by means of radiotherapy, chemotherapy and/or surgery.
. Lymph node dissection is indicated if there is evidence of nodal
spread (e.g. positive cytology).
. Following total laryngectomy, 60% of patients develop reason-
able oesophageal speech. Many patients are now provided with
a valve fitted to a tracheopharyngeal fistula. Phonation is pro-
duced by occluding the tracheostomy with a finger.
. Tracheostomy care training, speech therapy and social support
are important aspects of management.
. Recent evidence indicates that induction chemotherapy can
achieve an excellent response and increased rates of larynx
preservation in patients with locally advanced disease.
Prognosis
. The cure rates for T1 and T2 lesions are 90% and 65%,
respectively.
. The 5-year survival rate for T3 tumours is 25%.
10 Lung cancer
Epidemiology
. This is the commonest form of cancer in Western countries.
Aetiology
. Prolonged exposure to cigarette smoke is the most important
aetiological factor. This increases the risk by 53-fold.
. Asbestos exposure.
. Industrial pollution (e.g. coal and tar fumes, diesel exhausts,
nickel, zinc, beryllium, radon).
. Occupational exposure to nickel, chromium, iron oxide or
arsenicals.
. Pre-existing lung disease such as old TB and fibrosis (scar
carcinomas).
Pathology
. Squamous-cell carcinoma (which accounts for 40% of cases)
tends to arise proximally in large bronchi. It is associated with
loss of heterozygosity of the p53 gene.
. In small-cell lung cancer (20% of cases) neurosecretory gran-
ules are often present and produce various hormones (e.g.
calcitonin, ADH, ACTH, PTH). It is associated with over-
expression of C-myc and loss of heterozygosity of the p53 gene.
. Adenocarcinoma (15–50% of cases) tends to arise in scars
and peripheral sites. It is more common in women. It may be
bronchoalveolar or bronchoacinar. It is less strongly associated
with smoking than the other types.
31
. Large-cell carcinoma (10% of cases).

. Mixed histologies (15% of cases).
. Carcinoid tumours (< 1% of cases).
. Sarcoma (< 1% of cases).
Carcinoma of the bronchus spreads by local invasion and by
lymphatic and haematogenous routes.
Clinical features
. The commonest symptoms are haemoptysis, cough, dyspnoea
and chest pain.
. Other features include:
– hoarseness
– pleural effusion
– phrenic nerve palsy
– pneumonia
– pulmonary collapse
– dysphagia
– stridor
– superior vena cava obstruction (SVCO)
– Pancoast’s tumour
– mass in the neck
– bone metastases
– anorexia
– weight loss
– hypercalcaemia
– SIADH (syndrome of inappropriate ADH secretion)
– Cushing’s syndrome
– features of metastases to brain and intraperitoneal cavity.
Investigations
. CXR.
. Exfoliative sputum cytology (four specimens).
. Bronchoscopy and biopsy.
Lung cancer 33
. CT scanning to guide thoracic needle biopsy and to define

tumour extent.
. MRI to assess spread to cardiovascular organs.
. Mediastinoscopy to assess extent of disease.
. Other investigations include:
– FBC
– serum biochemistry
– bone scan
– liver USS
– brain CT
– lymph node biopsy
– pleural fluid cytology, etc.
Staging (TNM system)

. Stage I:
– T1,2N0M0
– T1N1M0.
. Stage II:
– T2N1M0.
. Stage III:
– any T3
– any N2
– any M1.
Treatment and prognosis

. Non-small-cell lung cancer (NSCLC).
– Less than 50% of cases are resectable at the time of diag-
nosis.
– Operable cases may be treated by wedge excision (for
localised peripheral tumours), lobectomy (for more centrally
located tumours) or pneumectomy (for tumours of the main
bronchus where more than one lobe is involved or the hilum
is involved).
– The 5-year survival rate for resectable tumours is 55% for

stage I, 30% for stage II and 18% for stage III. T1 squamous-
cell tumours have the best survival rate (80%).
– Radical radiotherapy (60 Gy over 6 weeks) is indicated in
patients who have resectable tumours but who are unfit for
or refuse surgery. The 5-year survival rate is 10%.
– Palliative radiotherapy to relieve troublesome symptoms in
patients with inoperable disease.
– Chemotherapy has a limited role in localised NSCLC. The
benefit is estimated to be 5%. Drugs used include taxanes,
mitomycin, cisplatin, cyclophosphamide, doxorubicin, etc.
The drugs may be given in combination before or after
radiotherapy or surgery.
. Small-cell lung cancer (SCLC).
– The majority of patients present with extensive disease.
– Radiotherapy is the mainstay of treatment for loco-regional
disease and metastases. The primary tumour response rate is
80% with 50 Gy over 5 weeks.
– Combination chemotherapy (doxorubicin, etoposide and
cyclophosphamide) is indicated in fit patients.
– The 2-year survival rate for limited disease is 15%.
Biological therapy
. Recent clinical trials have failed to demonstrate any superiority
for Iressa (an EGFR antagonist) compared with placebo in
patients with locally advanced or metastatic NSCLC that is
refractory to chemotherapy.
. Introduction of the wild-type p53 plus a viral vector (e.g. an
adenovirus) into advanced pulmonary tumours is currently
being investigated. The initial results are encouraging.
11 Breast cancer
Epidemiology
. Breast cancer is the leading cause of death among women.
. The lifetime risk is approximately 10%.
. The average incidence is 65 per 100 000 individuals per year.
Aetiology
. Risk factors include:
– early menarche (the relative risk is 1.5)
– late menopause (early menopause is protective)
– obesity after the menopause (pre-menopausal obesity is
protective)
– nulliparity (increases risk by 30%)
– late pregnancy (e.g. after the age of 35 years)
– benign breast disease, especially atypical epithelial hyper-
plasia
– oral contraceptives
– hormone replacement therapy (seems to increase the risk by
35% after use for 5 years)
– family history of breast cancer. The risk is particularly high
in the first-degree relatives of patients with early onset of
breast cancer (age < 45 years) and/or bilateral breast cancer
– alcohol consumption is associated with increased risk
– ionising radiation. The risk increases with radiation dose.
Exposure during the second decade has a maximal risk. The
latency period is 15–20 years
– elevated serum insulin-like growth factor type 1 (IGF-1).
35
Screening
. Screening mammography is recommended for:
– all women aged 50–69 years (every 2 years)
– all women aged 40–49 years (every 12–18 months)
– all women with a previous history of breast cancer or a
significant family history of breast cancer (annual mam-
mography).
. Screening mammography has been shown to reduce breast
cancer mortality by 30% in women aged over 50 years.
. There is increasing evidence that MRI is effective in screening
high-risk young women with dense breasts.
Pathology
. Ductal carcinoma in situ (DCIS) is confined to the duct-lobular
units without breaching the basement membrane. It is
subclassified into:
– low nuclear grade, with or without necrosis
– intermediate nuclear grade, with or without necrosis
– high nuclear grade, with or without necrosis.
The risk of developing into invasive cancer is greatest for high-
grade DCIS associated with necrosis.
. Lobular carcinoma in situ (LCIS). This is a marker of increased
risk of developing breast cancer. The risk of developing invas-
ive cancer is approximately 25% after 20 years. The invasive
lesion may be ductal.
. Infiltrating ductal carcinoma. This is the commonest type.
. Infiltrating lobular carcinoma. This type is associated with a
higher incidence of bilateral breast cancer, and its extent is
frequently underestimated by breast imaging.
. Colloid carcinoma:
– accounts for 5% of breast cancers
– has a good prognosis.
. Tubular carcinoma has an excellent prognosis.
. Cribriform carcinoma is rare and has a good prognosis.
Breast cancer 37
. Papillary carcinoma is rare and has a good prognosis.

. Medullary carcinoma has a good prognosis and is associated
with a family history of breast cancer.
. Paget’s disease of the breast, in which there is skin infiltration
by large pale-staining malignant cells.
. Inflammatory carcinoma accounts for 2% of all cases. There is
erythema, tenderness and invasion of the dermal lymphatics by
tumour cells. It has a poor prognosis.
. Squamous-cell carcinoma:
– is a rare tumour and usually lacks hormone receptors
– the prognosis is similar to that of infiltrating ductal cell
carcinoma
– a primary extra-mammary lesion should be excluded.
Clinical features
. Symptoms include:
– breast lump (85% of cases)
– pain (5%)
– nipple retraction (5%)
– nipple discharge (2%)
– Paget’s disease (5%)
– axillary mass (1%)
– skin changes (1%)
– distant metastases.
. Clinical examination usually reveals a solid mass which may be
ill-defined and fixed to overlying/underlying structures.
. The loco-regional lymph nodes, thoracic spine and abdomen
should be examined in the search for metastases.
. Breast cancer may present as an impalpable mammographic
abnormality during screening. DCIS accounts for 20% of
screen-detected cancers and usually presents as pleomorphic
microcalcifications.
Investigations
. FNAC:
– has a high specificity (> 98%) in the hands of experienced
cytologists
– cannot distinguish between infiltrating and in-situ lesions
– can be performed stereotactically and can be ultrasound
guided.
. Core biopsy:
– specificity approaches 100%
– is indicated if neoadjuvant chemotherapy is considered, if
mastectomy is planned, for impalpable microcalcification
(under stereotactic guidance) and if FNAC is equivocal.
. Mammography:
– signs of malignancy, including spiculated masses, circum-
scribed masses, microcalcifications, stellate lesions, paren-
chymal distortions, skin tethering and retraction and nipple
inversion.
. Ultrasound examination (with or without Doppler).
. Cytological analysis of scrape smear (of nipple) and nipple
discharge.
. MRI of the breast is useful for estimating the extent of disease
and assessing response to neoadjuvant therapy.
. Investigations for suspected metastatic disease include:
– FBC, serum biochemistry and CXR (all patients)
– liver USS and bone scan for patients with symptoms/signs
suggestive of metastatic disease, abnormal serum biochem-
istry or grossly involved axillary nodes
– bone MRI if bone scan is equivocal
– computed tomography (CT) and/or positron emission tom-
ography (PET) for suspected lung metastases.
Management
. Localised invasive breast cancer.
– Breast-conserving surgery (BCS) entails wide local excision
of the tumour and axillary dissection. The sentinel-node
Breast cancer 39
biopsy (SNB) using the dual localisation technique should be

considered in all patients with clinically node-negative early
breast cancer, and if the SNB is positive for malignancy on
intra-operative frozen section, complete axillary clearance is
performed.
– Mastectomy is indicated for central tumours, multi-centric
disease, Paget’s disease of the breast, large tumours (> 4 cm in
diameter), or if the patient requests mastectomy. Immediate
breast reconstruction should be offered to fit patients who
are undergoing mastectomy.
– Adjuvant radiotherapy (RT) is indicated after BCS (all cases).
Post-mastectomy RT is indicated if the tumour is node-positive
(four or more positive nodes) or incompletely excised.
– Adjuvant tamoxifen is indicated if the tumour is ER and/or
progesterone receptor (PgR) positive.
– Adjuvant cytotoxic chemotherapy (anthracycline based) is
indicated for fit patients with node-positive disease or with
high-risk (e.g. ER-negative, grade III and/or large size) node-
negative disease.
. DCIS.
– Wide local excision with adequate margins is the mainstay of
management.
– Adjuvant RT is indicated after BCS, especially if the tumour
is large in size, of high grade or close to the excision margins.
– Mastectomy is indicated for multi-centric disease, large
lesions, Paget’s disease or if the patient requests mastectomy.
No adjuvant RT is required after mastectomy. Immediate
breast reconstruction should be offered.
– Tamoxifen is not currently indicated for DCIS. It may be
considered if DCIS is of high grade, large size and close to or
involving the excision margins, especially in women younger
than 50 years (when no further surgery is possible).
– Formal axillary-node dissection is not indicated for DCIS.
The sentinel-node biopsy may be considered for high-risk
DCIS treated by mastectomy.
. Locally advanced breast cancer (LABC).
– Initial treatment consists of systemic therapy (endocrine or
cytotoxic) and/or RT. Subsequent treatment includes BCS or
total mastectomy.
– Post-menopausal women with ER- and/or PgR-positive LABC

can be treated with an aromatase inhibitor (e.g. letrozole or
anastrozole).
– Pre-menopausal women with ER- and/or PgR-positive LABC
can be treated with goserelin.
– ER- and PgR-negative LABC is treated by cytotoxic therapy
(e.g. taxanes and anthracyclines).
– USS, MRI and/or Ki-67 expression can be used to monitor
response.
. Metastatic breast cancer (MBC).
– ER and/or PgR positive MBC is treated with an aromatase
inhibitor (anastrozole, letrozole or exemestane) in post-
menopausal patients, and with goserelin (plus tamoxifen
or an aromatase inhibitor) in pre-menopausal patients.
– Cytotoxic therapy (taxanes and anthracyclines) is indicated
for ER- and PgR-negative disease. Xeloda is an oral therapy
that seems to improve survival when added to Taxotere.
– Herceptin, either as monotherapy or in combination with
Taxol, is indicated for HER2-positive (immunohistochemistry
(IHC) score of 3 or more or FISH positive) disease.
– Bisphosphonates are indicated for multiple bone metastases.
– RT is indicated for painful localised bone or brain metastases.
– Palliative measures include analgesia, thoracostomy tubes
and pleurodesis, and drainage of ascites.
. Breast care counsellors play an important part in the manage-
ment of patients, and provide psychological support and in-
formation.
. All patients who are undergoing mastectomy should be offered
immediate breast reconstruction (IBR). If IBR is considered,
then skin-sparing mastectomy combined with a mammary
implant and/or a myocutaneous flap achieves an excellent
cosmetic result without compromising oncological safety. The
flap can be either a latissimus dorsi (LD) or a transverse rectus
abdominus myocutaneous (TRAM) flap. TRAM flaps can be
either conventional or free transfer, and do not usually require
a prosthesis. Muscle-sparing free-transfer flaps based on the
deep inferior epigastric perforator (DIEP) are increasing in
popularity. The latter technique should be delayed if possible in
cases where post-mastectomy RT is indicated.
Breast cancer 41
Prognosis
. Axillary-node status is the best single predictor of prognosis.
. Other prognostic parameters include tumour size, tumour
grade, ER status, lymphovascular invasion, expression of
p53, Ki-67 and HER2, microvessel density and bone-marrow
micrometastases.
. The 5-year disease-free survival rate is 95% for stage 0 (DCIS),
85% for stage I, 70% for stage II, 50% for stage III and 15% for
stage IV.
. Around 98% of DCIS lesions are cured by mastectomy.
Follow-up
. Six-monthly review for 2 years and then annual review for
3 years.
. Annual mammography.
Familial breast cancer (FBC)

. This accounts for 5% of all breast cancers.
. Genes responsible include the BRCA-1 gene (also responsible
for ovarian cancer) on 17q21, the BRCA-2 gene on 13q12–13,
the p53 gene on 17p13, the ataxia telangiectasia gene on 11q23
and the androgen-receptor gene on the X-chromosome.
. FBC can be treated with breast-conserving surgery plus RT.
. Prophylactic bilateral mastectomy can reduce the risk by 90%
in patients carrying BRCA genes. Tamoxifen and ovarian
ablation are also likely to reduce the risk.
Recent advances and future

prospects
. Third-generation aromatase inhibitors (letrozole, anastrozole
and exemestane) are becoming the drugs of choice for the
treatment of advanced post-menopausal breast cancer which is
ER- and/or PgR-positive as first-line and second-line agents.
. The ATAC trial has recently reported its preliminary results
after a median follow-up of 47 months. It has demonstrated
that adjuvant anastrozole is superior to tamoxifen in reducing
the risk of local recurrence and preventing contralateral breast
cancer in post-menopausal women with hormone-sensitive
disease. Although further follow-up is required, anastrozole
can be used as an adjuvant therapy if tamoxifen is contra-
indicated (e.g. if there is a history of deep vein thrombosis and
endometrial hyperplasia/cancer) or cannot be tolerated. Bisphos-
phonates, vitamin D and calcium can be added to anastrozole
in women who are at risk of osteoporosis.
. Faslodex (250 mg IM once monthly) is a selective oestrogen-
receptor down-regulator. Recent phase III clinical trials have
demonstrated that it is at least as effective as anastrozole in
post-menopausal patients with advanced disease who relapsed
or progressed on prior endocrine therapy. In the first-line
setting it is equivalent to tamoxifen, except in patients with
tumours that are ER- and PgR-positive, where Faslodex seems
to be superior.
. Letrozole (an aromatase inhibitor) has recently been shown to
be an effective neoadjuvant agent in post-menopausal women
with ER- and/or PgR-positive tumours. The drug was found to
be superior in efficacy to tamoxifen, and increased the rate of
BCS in a phase III study. It is significantly more effective than
tamoxifen in patients with HER2 disease.
. Microarray gene profiling, which allows the identification of
thousands of genes, is likely to enter clinical practice within the
next five years. This new technology may improve the prog-
nosis prediction and guide therapy.
Breast cancer 43
. Digital mammography seems to achieve better-quality images

than conventional mammography. This new technology also
facilitates image storage and transmission, and allows the use
of computer-aided detection.
. Fibre-optic ductoscopy seems to be an effective diagnostic tool
in patients with pathological nipple discharge. It may have a
role in guiding breast cancer surgery and cancer detection.
. There is increasing evidence that cyclo-oxygenase type 2
(COX-2) plays an important role in mammary carcinogenesis
and angiogenesis. Selective COX-2 inhibitors may therefore
prove to be effective in the treatment and prevention of breast
cancer. Clinical trials are currently in progress.
. Aromatase inhibitors (e.g. letrozole) have a potential role in
extended adjuvant therapy after 5 years of tamoxifen treat-
ment and in sequential therapy after 2–3 years of tamoxifen
treatment.
. Proteomics is likely to have a role in breast cancer detection.
. Electrical impedance and conductance and thermovascular
measurements may have a role in cancer detection.
. Localised radiotherapy may prove as effective as and even
replace whole breast irradiation.
12 Oesophageal
cancer
Epidemiology
. The incidence ranges from 3 to 180 per 100 000 per year,
depending upon geographical location.
. There is a geographical clustering in certain parts of Asia and
Africa.
. The incidence of adenocarcinoma (mostly located distally) has
been increasing.
Aetiology
Risk factors include:
. Barrett’s oesophagus (13% risk). High-grade dysplasia is asso-
ciated with the highest risk
. achalasia
. corrosive strictures
. diverticular disease of the oesophagus
. Plummer–Vinson syndrome
. smoking, alcohol consumption, the rubber industry, vitamin C
deficiency, human papilloma virus (a minor role), zinc defi-
ciency and tylosis.
44
Oesophageal cancer 45
Pathology
. In Asia, 80% of carcinomas are of the squamous-cell type and
15% are adenocarcinomas. The middle third is the commonest
location.
. In Western countries, 45% of carcinomas are adenocarcinomas
and 50% are squamous-cell carcinomas. Lesions of the lower
oesophagus and cardia are more common in these countries.
. Dysphagia (95% of cases).
. Regurgitation (45%).
. Weight loss (40%).
. Cough (25%).
. Pain (20%).
. Hoarse voice (20%).
. Dyspnoea (5%).
. Haemoptysis (5%).
. Haematemesis (5%).
. Neck mass (5%).
. Anaemia.
Physical examination
. Search for metastases in the neck (Virchow’s node), abdomen
and pelvis.
Investigations
. Double-contrast barium swallow.
. Upper GI endoscopy (biopsy or brush cytology).
. Endoscopic ultrasound (most precise staging investigation of
tumour’s depth, but not for nodal status).
. CT or MRI of thorax and abdomen.
. Preliminary studies have suggested that fluoro-2-deoxy-D-

glucose positron emission tomography (FDG-PET) can detect
otherwise radiographically occult distant metastatic disease.
– FBC
– liver function tests (LFTs)
– CXR
– bronchoscopy
– abdominal USS.
Treatment
. Oesophageal resection:
– is indicated for operable tumours (40% of all cases)
– requires peri-operative intensive-care facilities and careful
patient selection
– pre-operative chemotherapy and radiation may be required
to downstage advanced tumours to render them operable
– a proximal margin of 10 cm is preferable
– should be combined with removal of regional lymph nodes in
juxtaposition
– the Ivor–Lewis operation is suitable for tumours of the
middle and lower thirds. The operation usually requires a
laparotomy and a thoracotomy. The stomach is pulled through
for anastomosis with the proximal oesophagus and a pyloro-
plasty is performed
– for tumours of the upper third, McKeown’s procedure (lap-
arotomy, right thoracotomy and left neck incision) or a
sternotomy approach is used. A stomach pull-through or
a jejunal Roux-en-Y can be performed. In some cases,
laryngectomy, tracheostomy, pharyngectomy and/or total
oesophagectomy may be required
– thoracoscopic dissection of the oesophagus has recently been
developed
– surgery also has a palliative role (surgical bypass).
. Radiotherapy:
– response rate is 35%
Oesophageal cancer 47
– complete eradication rate is 5%

– side-effects include strictures, cardiac and pulmonary dam-
age, bleeding and malignant oesophago-tracheo-bronchial
fistula formation.
. Intubation:
– is indicated for advanced and non-resectable tumours and
for unfit patients
– pulsion or traction technique may be used
– the funnel of the tube sits proximal to the tumour
– self-expanding metal stents have been used recently with
good results
– the risk of perforation is 10%
– intubation is contraindicated in cervical lesions.
. Laser therapy:
– Nd:YAG laser therapy provides temporary palliation.
. Chemotherapy:
– there is increasing evidence that chemotherapy (e.g. 5-FU
and cisplatin) is effective in oesophageal cancer. Tumour
regression occurs in 60% of cases.
Prognosis
. The 5-year survival rate is 18% for surgical resection.
. Survival rates have been improving due to increased surgical
expertise, careful patient selection, use of a multi-modality
approach, and earlier detection.
13 Gastric cancer
Epidemiology
. The incidence is 23 per 100 000 per year (declining worldwide).
. It accounts for 6% of all cancer deaths.
. The peak incidence is in the age range 50–70 years.
. The highest incidence is in Japan.
. Pre-malignant changes include chronic atrophic gastritis, in-
testinal metaplasia and dysplasia.
. Risk factors include Helicobacter pylori infection, blood group
A, high intake of salt and salt-cured meats, vitamin deficiency
(vitamins A, C and E), high intake of nitrates and selenium
deficiency.
. Various genetic alterations have been linked to gastric cancer
(e.g. p53, C-myc and C-erb B2).
Pathology
. The lesion may be polypoid, ulcerative, diffuse or ulcerative/
diffuse.
. Around 35% of lesions arise in the proximal third.
Staging
. TNM system (1997 edition).
. The regional lymph nodes include the perigastric nodes, the
nodes along the left gastric common hepatic, splenic and coel-
iac arteries, and the nodes in the hepatoduodenal ligaments.
. N0: no regional node involvement.
48
Gastric cancer 49
. N1: metastasis in 1–6 regional nodes.

. N2: metastasis in 7–15 regional nodes.
. N3: metastasis in more than 15 regional nodes.
Clinical features
. Dysphagia.
. Vomiting.
. Abdominal pain (50% of cases).
. Epigastric mass (20%).
. Microcytic anaemia.
. Weight loss and cachexia.
. Other features include:
– Krukenberg’s tumour
– venous thrombosis
– left supraclavicular lymphadenopathy.
Investigations
. FBC, serum biochemistry.
. Upper GI endoscopy (and biopsy) and barium meal.
. CT or MRI and/or USS for staging.
Treatment
. Gastrectomy.
– This is possible in 65% of cases.
– Access is through a transverse subcostal incision, vertical
midline incision or Ivor–Lewis approach.
– It entails sufficient resection margins, omentectomy and
lymphadenectomy.
– D1 resection is indicated for pT1 tumours and D2 (extended
lymph-node dissection) resection for tumours with serosal
involvement. The pancreas and spleen should be preserved if
possible.
– There is no evidence that D2 resection improves survival in

early gastric cancer, but it may have benefit in tumours > T3.
– For proximal tumours, oesophageal resection may be required
in order to achieve a 10 cm proximal margin.
– Billroth II reconstruction is indicated for distal tumours.
– Radical total gastrectomy and oesophago-jejunostomy
(Roux-en-Y) are indicated for extensive tumours.
– Gastrectomy for early disease can be performed laparo-
scopically. Randomised controlled trials comparing laparo-
scopic gastrectomy with the open approach are required.
. Adjuvant chemotherapy (5-FU plus leucovorin) is considered if
more than three nodes are involved.
. Post-operative chemoradiation seems to improve the survival
of patients with chemosensitive locally advanced disease.
. Radiotherapy may be given pre-, intra- or post-operatively.
Some tumours are rendered operable by neoadjuvant chemo-
therapy.
. Chemotherapy (5-FU, mitomycin C and adriamycin) may be
given in cases of advanced disease.
. Palliative procedures include gastroenterostomy (ante-colic),
intubation, dilatation and laser treatment.
Prognosis
. The 5-year survival rate is 80% for stage IA (T1N0M0) and
10% for stage IV (T4N1–3M0T1–3N3M0 and TanyNanyM1).
14
Gastrointestinal
lymphoma (GIL)
Epidemiology
. This represents 5% of all GI malignancies and 10% of extra-
nodal non-Hodgkin’s lymphoma.
. It is essential to distinguish between primary GIL and second-
ary involvement of the GI tract.
. The peak incidence occurs in the age range 50–70 years.
. The incidence of anorectal lymphoma is rising.
. The stomach is the commonest site for GIL (35–79% of cases).
Aetiology
. Malignant transformation of mucosa-associated lymphatic
tissue (MALT) seems to be important in pathogenesis.
. Predisposing factors include:
– atrophic gastritis (Helicobacter pylori)
– a-chain disease
– coeliac disease
– dermatitis herpetiformis
– Crohn’s disease
– autoimmune disorders
– immunodeficiency syndromes, including AIDS.
51
Pathology
. Stage I: tumour confined to GI organs.
. Stage II: tumour with intra-abdominal lymph node involve-
ment.
. Stage III: extra-abdominal nodes or other organs involved.
. Stage IV: disseminated disease.
There are three main types:
. western lymphoma (non-Hodgkin’s B-cell lymphoma)
. primary lymphoma associated with coeliac disease (T-cell
lymphoma)
. Mediterranean lymphoma associated with a-chain disease.
Clinical features
. Symptoms include:
– abdominal pain
– nausea
– vomiting
– weight loss
– fatigue.
. Physical examination may reveal an abdominal mass (35% of
cases) and anaemia.
. Symptoms and signs of obstruction, perforation or haemorrhage.
Investigations
. FBC, serum U&Es and LFTs.
. CXR (with thoracic CT).
. Abdominal ultrasonography.
. Abdomino-pelvic CT.
. Gastrointestinal endoscopy (with biopsy).
. Endosonography.
. Barium studies of the GI tract.
. Faecal occult blood testing.
Gastrointestinal lymphoma (GIL) 53
. Southern blot DNA hybridisation of fresh biopsy specimens.

. Laparotomy/laparoscopy.
Management
. Treatment depends upon the site, stage and histological
subtype.
– Stage I and II disease is treated by resection of the involved
segment (e.g. subtotal gastrectomy, right hemicolectomy,
etc.) with the regional lymph nodes. Post-operative radio-
therapy (25 Gy to the whole abdomen with a boost of 15 Gy
to the tumour region) and adjuvant chemotherapy with
cyclophosphamide, doxorubicin, vincristine and prednisolone
(CHOP) are recommended if the lesion is high grade and/or
the margins of the resection specimens are involved in the
disease.
– Stage III and IV disease is treated by chemotherapy
(cyclophosphamide, doxorubicin hydrochloride, oncovin
and prednisolone (CHOP)) and radiotherapy, with a 50%
response rate. Surgical intervention is reserved for compli-
cations such as obstruction, haemorrhage and perforation.
Prognosis
. The 5-year survival rate for stages I and II is 70% for com-
pletely resected tumours and 40% for incompletely resected
lesions.
. The 5-year survival rate for stages III and IV is 20%.
15 Small bowel
carcinoma
Epidemiology
. This accounts for 40% of all small bowel malignancies. The
latter account for 5% of all GI malignancies.
. The average age at presentation is 50 years.
. The duodenum and proximal jejunum are the commonest sites.
Aetiology
. Predisposing factors include Crohn’s disease, coeliac disease,
Peutz–Jegher’s syndrome, adenomatous polyps and polyposis
syndromes.
Clinical features
. Symptoms include:
– diarrhoea
– anaemia
– abdominal pain
– nausea
– vomiting
– haemorrhage
– perforation
– intermittent jaundice (duodenal lesions)
– anorexia
– weight loss.
54
Small bowel carcinoma 55
. Signs include:
– anaemia
– abdominal mass
– jaundice
– signs of obstruction or perforation.
Investigations
. FBC, serum U&Es, LFTs, faecal occult blood testing.
. Barium meal and follow-through series reveal tumour in 50%
of cases.
. GI endoscopy and biopsy.
. CXR.
. Abdominal USS and/or CT.
. Laparoscopy/laparotomy.
Management
. Wide surgical resection including the regional lymph nodes is
the mainstay of management.
. Whipple’s operation may be necessary for duodenal lesions.
. Surgical palliation may involve intestinal resection or bypass.
. Radiotherapy and chemotherapy play little role in treatment.
. The role of nitrosoureas and 5-FU is currently being investigated.
Prognosis
. The lesions are usually advanced at the time of diagnosis.
. The incidence of metastases is approximately 70% at the time
of laparotomy.
. The 5-year survival rate is 35% for duodenal lesions and 20%
for lesions elsewhere.
Note: Other primary malignancies of the small bowel include:
. carcinoids (30%)
. lymphoma (18%)
. sarcoma (15%).
16 Colorectal
carcinoma
Epidemiology
. The incidence ranges from 0.4 per 100 000 per year (in Nigeria)
to 32.3 per 100 000 per year (in the USA).
Aetiology
– familial polyposis coli (FPC)
– Lynch syndrome I and II
– high intake of dietary fat
– low intake of dietary fibre
– obesity
– high alcohol intake
– bile acids
– tobacco smoking
– asbestos
– ulcerative colitis
– Crohn’s disease
– family history of colorectal cancer
– previous history of colorectal polyps or cancer
– ureterosigmoidostomy.
. The adenoma–carcinoma sequence is important in colorectal
carcinogenesis.
. Genetic alterations in growth suppressor genes (p53 and
BRCA-1) and oncogenes (K-ras) cause tissue change from
normal epithelium to adenoma and then carcinoma.
. COX-2 inhibitors seem to reduce the risk.
56
Colorectal carcinoma 57
Screening
. Patients with colorectal cancer, polyps, ulcerative colitis and a
family history of polyposis syndromes should be screened with
colonoscopy.
. Other screening methods include barium enema, flexible sig-
moidoscopy and faecal occult blood (FOB) testing.
Pathology
. Around 98% of cancers are adenocarcinomas. The tumour is
confined to the mucosal and sub-mucosal layers in Dukes’ A,
has penetrated the bowel wall (muscularis mucosa) in Dukes’
B, and there is regional lymph node involvement in Dukes’ C.
There are distant metastases in Dukes’ D.
. The incidence of lymph node metastasis depends upon the
tumour grade and the presence of p53 oncogenes.
Clinical features
. Large bowel obstruction (more likely with left-sided lesions).
. Perforation and peritonitis.
. Altered bowel habits.
. Rectal bleeding.
. Microcytic anaemia (more likely with right-sided lesions).
. Small bowel obstruction (e.g. caecal carcinoma).
. Abdominal mass.
. Symptoms and signs of metastasis (e.g. hepatomegaly and
ascites).
Investigations
. Proctosigmoidoscopy.
. FBC.
. LFTs.
. Serum carcino-embryonic antigen (CEA).

. Barium enema.
. Colonoscopy.
. Abdominal ultrasonography (including liver).
. Endoscopic biopsy.
. Abdomino-pelvic CT.
– IVU for suspected ureter involvement
– bone scan
– CXR and brain CT for suspected metastases.
Treatment
. Surgical excision is the main treatment. Right hemicolectomy,
transverse colectomy, left hemicolectomy, sigmoid colectomy,
anterior and abdominoperineal excision of the rectum may be
performed.
– The amount of large bowel removed depends upon the
aetiology, arterial blood supply, grade of differentiation,
quality of the anal sphincters and the patient’s age and
fitness.
– A permanent stoma is necessary if the tumour invades the
anal sphincters, if the tumour is located within 5 cm of the
dentate line and is poorly differentiated or if the anal sphinc-
ters are weak and uncontrollable and incontinence is likely.
– The distal clearance margin should be 2 cm for well-
differentiated tumours and 5 cm for poorly differentiated
tumours.
– Total excision of the mesorectum reduces the incidence of
local recurrence of rectal cancer and prolongs survival.
– Radiotherapy administered pre-operatively or post-operatively
improves disease-free survival in patients with rectal carci-
noma.
– A loop ileostomy may be performed to protect a low anas-
tomosis.
– Subtotal colectomy and ileo-rectal anastomosis is indicated
in cases of FPC, Lynch syndrome and younger patients with
left-sided obstruction.
Colorectal carcinoma 59
– A colonic pouch–anal anastomosis may be performed for

very low rectal tumours.
– The role of laparoscopic surgery and sentinel-node biopsy in
the surgical treatment of colorectal cancer is currently under
investigation.
. Adjuvant chemotherapy (5-FU plus folinic acid infusion) for
6 months is indicated for stage II rectal cancer and stage III
colonic and rectal carcinoma.
. The addition of oxaliplatin or capecitabine to 5-FU and folinic
acid infusion seems to improve survival in patients with meta-
static disease.
. Biological therapy with monoclonal antibodies against vascu-
lar endothelial growth factor (bevacizumab) or epidermal growth
factor (cetuximab) seems to be effective in the treatment of
metastatic disease.
. Radiotherapy is indicated in rectal cancer (Dukes’ B and C).
It may be given post-operatively or pre-operatively. It is also
useful for inoperable or recurrent cancers.
. Management of locally advanced disease.
– En bloc surgical excision is the mainstay of management.
– Ureter involvement can be managed with ureteroureter-
ostomy, Boari flap reconstruction, ileal conduit, ureterostomy,
spout colostomy diversion or nephrostomy.
– For rectal cancer, radiotherapy (with or without chemo-
therapy) may be given pre-operatively to shrink tumours or
post-operatively for involved margins.
– Chemotherapy in the form of systemic 5-FU/folinic acid
infusion should be given to fit patients. Recent evidence
suggests that regimens containing irinotecan, oxaliplatin
and/or bevacizumab (monoclonal antibody directed against
vascular endothelial growth factor) are more effective than
standard 5-FU plus folinic acid infusion in patients with
advanced colorectal cancer.
. Management of liver metastases.
– Hepatic resection is possible in 25% of cases, and the 5-year
survival rate is 20% after surgery. Post-operative regional
(intra-arterial/portal) chemotherapy reduces the relapse rate.
– Systemic 5-FU and folinic acid may be given for inoperable

liver metastases, with a 30% response rate. Raltitrexed is
effective in the palliation of metastatic disease.
. Management of other metastases.
– Radiotherapy is indicated for bony metastases.
– Radiotherapy and corticosteroids are indicated for brain
metastases.
. Management of local recurrence.
– Clinical local recurrence occurs in around 10% of cases.
– Around 70% of patients with local recurrence have distant
metastases.
– Treatment modalities include surgical excision, endoluminal
excision (using diathermy or laser) and/or radiotherapy.
Prognosis
. The 5-year survival rate is 90% for Dukes’ A, 55% for Dukes’
B, 30% for Dukes’ C and 15% for Dukes’ D.
Follow-up
. History and examination (including rigid sigmoidoscopy) are
performed every 3 months for the first 3 years and then every
6 months thereafter.
. Serum CEA may be measured regularly.
. Colonoscopic surveillance should be undertaken every 4 years
for patients presenting with a single cancer and every 2 years
for those presenting with multiple cancers.
17 Anal cancer
Epidemiology
. The incidence ranges from 0.2 per 100 000 per year (in the
Philippines) to 3.6 per 100 000 per year (in Switzerland).
. The incidence is increasing worldwide.
Aetiology
– receptive anal intercourse
– human papilloma virus (HPV) types 16, 18, 31 and 33
– herpes simplex virus type II
– Chlamydia and HIV infection.
Pathology
. Around 80% of lesions are epidermoid, and the remainder
consist of melanoma and adenocarcinoma.
. Local spread tends to occur in the cephalad direction.
. Nodal spread to perirectal, inguinal and lateral pelvic nodes
may occur.
Clinical features
. Pain and bleeding in 50% of cases.
. Anal mass/ulcer, faecal incontinence and/or ano-vaginal fistula.
. Inguinal lymphadenopathy in 30% of cases (metastases are
confirmed in only 50% of such cases).
. Hepatomegaly (uncommon).
61
Investigations
. Proctoscopy and biopsy.
. Examination under anaesthetic (EUA) and biopsy.
. Endo-anal USS.
. CT or MRI.
Treatment
. Combined radiotherapy (50 Gy) and chemotherapy (5-FU and
mitomycin C) is the mainstay of management (Nigro’s regimen).
. Surgical treatment is indicated for failure of primary non-
surgical therapy (residual tumour, radionecrosis, fistulae and
local recurrence), for small lesions at the anal margin and for
inguinal recurrence after radiotherapy.
. Surgical procedures include abdominoperineal resection, de-
functioning colostomy, excision of peri-anal lesions and inguinal
node dissection.
. Adenocarcinoma is usually treated with abdominoperineal
resection, and melanoma is treated with more conservative
surgery due to the poor prognosis.
Prognosis
. The overall 5-year survival rate for epidermoid carcinoma is
58%. The local control rate with radiotherapy and chemo-
therapy is 90%.
18 Gall bladder
cancer
Epidemiology
. Gall bladder cancer is found incidentally in 2% of all gall
bladders excised for gallstones.
Aetiology
. It is associated with gallstones in 75% of cases.
. Carcinogens, including nitrosamines and methylcholanthrene.
. A higher incidence is reported among those working in the
rubber industry and typhoid carriers.
Pathology
. The histological subtypes include adenocarcinoma (85%),
squamous-cell carcinoma (3%) and undifferentiated (7%).
. The tumour tends to invade locally.
. Spread may occur via the intraductal lymphatic or vascular
routes.
. The lesion appears macroscopically as a nodule, polypoid mass
or focal/diffuse thickening.
63
Clinical features
. Incidental finding in a cholecystectomy specimen.
. Pain (80% of cases), nausea and vomiting (50%), weight loss
(40%), jaundice (40%), abdominal distension (30%), pruritus
(15%) and melaena (3%).
. Hepatomegaly (40%), mass in the right hypochondrium (40%)
and upper abdominal tenderness (40%).
Investigations
. FBC and LFTs.
. Ultrasound, CT and/or MRI.
. Cholangiography (ERCP/PTC).
Nevin’s staging
. Stage I: mucosa only.
. Stage II: mucosa and muscularis.
. Stage III: transmural.
. Stage IV: transmural and cystic lymph node.
. Stage V: liver invasion/distant metastases.
Treatment
. Simple open cholecystectomy for stages I and II.
. Radical cholecystectomy, including adjacent liver resection
and regional lymph node dissection, for stages III and IV.
Pancreaticoduodenectomy is performed in selected cases. Rad-
ical surgery may be performed for stage V in fit patients.
. Palliative procedures include stenting (endoscopic or percu-
taneous) and surgical bypass (Roux-en-Y hepatico-jejunostomy).
. Intra-operative radiotherapy for stages III, IV and V.
Gall bladder cancer 65
Prognosis
. The 5-year survival rate is 60% for stage I, 40% for stage II,
10% for stage III, 7% for stage IV and 1% for stage V.
19
Cholangiocarcinoma
Epidemiology
. This accounts for 1.5% of all cancers.
. It is more common in the sixth and seventh decades and among
males.
Aetiology
– gallstones (found in 30% of cases)
– choledochal cysts
– Caroli’s disease
– sclerosing cholangitis
– ulcerative colitis
– Clonorchis sinesis infestation (liver fluke)
– Opsithorchis viverrini infestation
– thorium dioxide and drugs (OCP and methyldopa).
Pathology
. The common bile duct (CBD) is the commonest location (40%
of cases), followed by the common hepatic duct (32%), hepatic
duct bifurcation (20%) and cystic duct (5%).
. Adenocarcinoma is the commonest type (97%).
. The tumour may be peripheral (type I), hilar (type II), middle
third extrahepatic (type III) or distal extrahepatic (type IV).
66
Cholangiocarcinoma 67
Clinical features
. Jaundice is the commonest presentation (95%).
. Abdominal pain.
. Hepatomegaly.
. Pruritus.
. Abdominal tenderness.
. Ascites.
. Abnormal LFTs.
Investigations
. LFTs.
. Ultrasound, CT and/or MRI scan.
. Cholangiography (ERCP and/or PTC).
. Angiography or Doppler study to assess resectability.

. Resectable tumours of the distal third of the CBD are treated
with radical pancreaticoduodenectomy (Whipple’s procedure).
The 5-year survival rate is 50%.
. The resectable tumours of the middle third are treated with
excision (1 cm clear margin) and biliary–intestinal anastomosis
(hepatico-jejunostomy). The 5-year survival rate is 50%.
. For proximal hilar tumours, ‘attempt-at-cure’ surgery has been
proposed. The surgery involves local excision alone for type I,
local excision and partial hepatectomy for types II and III, or
orthoptic liver transplantation (OLT) for type IV. The 3-year
survival rate is 30%. The resectability rate is 20% (compared
with 65% for tumours of the middle and distal thirds of the
CBD).
. Partial hepatectomy or OLT is indicated for peripheral
cholangiocarcinoma. The 3-year survival rate is 50%.
. Palliative procedures for unresectable tumours or unfit patients

include stent placement (endoscopic or percutaneous trans-
hepatic) and surgical biliary–intestinal anastomosis. Self-
expandable stainless steel endoprostheses are preferable for
palliation. The median survival is 8 months.
. With regard to adjuvant therapy, chemotherapy and radio-
therapy have no established role in management as yet.
20 Hepatocellular
carcinoma (HCC)
Epidemiology
. This is the commonest primary cancer of the liver.
Aetiology
– aflatoxin and algal toxins
– hepatic cirrhosis
– viral hepatitis (B and C)
– haemochromatosis
– a1-antitrypsin deficiency
– tobacco smoking
– oestrogenic steroids
– autoimmune chronic hepatitis
– primary biliary cirrhosis
– Wilson’s disease.
Pathology
. The tumour type may be:
– diffuse
– single
– encapsulated
– fibrolamellar.
69
Clinical features
. Pain:
– epigastric
– right hypochondrium
– back.
. Anorexia.
. Dyspnoea (lung metastases/pleural effusion).
. Ascites.
. Hepatomegaly.
. Bleeding.
. Oesophageal varices.
. Obstructive jaundice.
. Bony metastases.
. Arterial murmur over the tumour.
. Paraneoplastic symptoms include:
– fever
– hypoglycaemia
– hypercalcaemia
– polycythaemia.
Investigations
. FBC, serum biochemistry and clotting screen.
. Serum a-fetoprotein (AFP) is a useful marker.
. Hepatitis screen (for hepatitis B and C).
. Abdominal (sunburst calcification) and chest X-ray.
. CT scan and ultrasound scan, angiography, Doppler flow
studies and/or portal venography.
. FNAC or core biopsy under radiological guidance. Biopsy should
be avoided in patients coming for resection or transplantation,
in order to prevent tumour spread along the needle track.
Treatment
. Peripheral wedge resection of small superficial carcinomas.
Hepatocellular carcinoma (HCC) 71
. Hepatic segmental resection is the mainstay of curative treat-

ment. Patients with multi-centric tumours, severe liver impair-
ment, ascites and distant metastases are excluded.
. Orthoptic liver transplantation should be offered to carefully
selected patients without dissemination who are not suitable
for segmental resection.
. Intra-arterial chemotherapy. The results of systemic chemo-
therapy remain disappointing.
. Interferon-a is effective, especially in reducing the recurrence
rate.
. Arterial embolisation is particularly effective in the manage-
ment of ruptured HCC.
– It is performed percutaneously using Gelfoam, Ivalon, steel
coils or starch microspheres.
– Post-embolisation syndrome consists of pyrexia, pain, nausea
and worsening LFTs.
– Arterial embolisation is contraindicated in the presence of
portal vein thrombosis.
. Percutaneous ethanol injection causes complete necrosis in
more than 90% of small tumours (< 3 cm in diameter).
. Radiotherapy may be given in the form of external beam
radiation, percutaneous injection of radioactive material or
transcatheter injection of [131I]-lipiodol.
. The role of tamoxifen is questionable.
Prognosis
. The 3-year survival rate for resection is 40%.
. The 3-year survival rate for transplantation is 25%.
. The 1-year survival rate for untreated patients is 20%.
21 Carcinoma of
the pancreas
Epidemiology
. The incidence ranges from 2 to 15 per 100 000 per year
depending upon geographical location. The incidence is in-
creasing.
. The female:male ratio is 3:1.
. The peak incidence is in the age range 60–80 years.
Aetiology
. Pancreatic cancer is associated with:
– cigarette smoking (2.5-fold increase in risk)
– high intake of animal fats and coffee
– pancreatitis (hereditary or chronic)
– ataxia telangiectasia.
Pathology
. The tumour type may be:
– ductal (82%)
– giant cell (6%)
– adenosquamous (4%)
– mucinous adenocarcinoma (2%)
– mucinous cystadenocarcinoma (1%)
– acinar-cell carcinoma (1%).
72
Carcinoma of the pancreas 73
Clinical features
. Jaundice (pancreatic head tumours).
. Pain.
. Weight loss.
. Pancreatitis.
. Upper GI haemorrhage.
. Thromboembolic disease.
. Cholangitis.
. Psychiatric disturbance.
. Thrombophlebitis.
. Migraine.
. Upper abdominal mass.
. Constipation.
. Bloating.
. Diarrhoea.
. Fatigue.
. Palpable gall bladder.
. Splenomegaly.
. Hepatomegaly.
. Diabetes mellitus.
Investigations
. FBC, serum U&Es, LFTs, clotting screen, ultrasonography,
ERCP and CT scanning.
. Brush cytology, FNAC or core biopsy under radiological guid-
ance.
. The staging investigations include:
– colour flow Doppler ultrasonography
– spiral CT scanning
– angiography
– laparoscopy
– endoscopic ultrasonography
– laparotomy.
Treatment
. Correction of clotting and electrolyte abnormalities.
. Surgical resection.
– This is indicated for small tumours (< 3 cm in diameter) and
favourable histological types in the absence of distant meta-
stases.
– It is possible in 8–25% of patients.
– Whipple’s operation is indicated for tumours of the head,
and distal pancreatectomy for tumours of the body and tail.
More radical resection does not improve survival.
– Whipple’s operation entails proximal pancreatectomy, gastro-
duodenal resection, cholecystectomy, pancreatico-jejunostomy,
choledochojejunostomy and gastrojejunostomy.
– The post-operative mortality rate should be less than 5%.
– The post-operative morbidity rate remains high (30–50%).
. Palliative surgery.
– Choledochoduodenostomy and retrocolic gastrojejunostomy.
– Endoscopic stent placement (self-expanding metal-mesh stents
are preferable).
– There is no difference in survival between surgical bypass
and stenting.
. Radiotherapy.
– This may be given adjuvantly after resection.
– Radiotherapy and 5-FU increase the survival rate in non-
resectable tumours.
. Chemotherapy.
– 5-FU and mitomycin seem to be effective agents. The objec-
tive response rate is 20%.
. Coeliac plexus block can be used for pain palliation.
. Biological therapy (e.g. angiogenesis inhibitors and immuno-
therapy) is likely to play a part in the treatment of this disease.
Carcinoma of the pancreas 75
Prognosis
. The median survival after surgical resection is 18 months (it is
longer for mucinous adenocarcinoma).
. The average survival after palliation is 5.4 months.
. The average 5-year survival rate is 2–5%.
22 Multiple
endocrine
neoplasia (MEN)
syndromes
. MEN I:
– autosomal dominant inheritance
– involves pituitary, islet cells of pancreas and parathyroid
glands
– thyroid adenomas, carcinoids, adrenal adenomas, thymomas
and ovarian tumours are associated with MEN I.
. MEN IIa:
– autosomal dominant inheritance
– includes medullary thyroid carcinoma (MTC), phaeo-
chromocytoma and parathyroid adenoma or hyperplasia.
. MEN IIb:
– autosomal dominant or sporadic
– includes phaeochromocytoma, MTC, submucosal neuromas,
ganglioneuromas and marfanoid habitus.
76
23 Insulinoma
Pathology
. Originates in the b-cells of the pancreatic islets.
. Around 90% of insulinomas are small single adenomas.
. Insulinomas associated with MEN I are multiple in 75% of
cases.
. Around 10% of insulinomas are malignant.
Clinical features
. The clinical picture is defined by Whipple’s triad:
– symptoms and signs of hypoglycaemia occurring during
fasting or exercise
– at the time of symptoms, the blood glucose level is below
60 mg/dl
– the symptoms are reversed by glucose administration.
Investigations
. Serum insulin:glucose ratio, which usually exceeds 1 in insulin-
oma patients.
. Localisation using selective venous sampling, angiography, CT
and/or MRI.
. Intra-operative USS.
. Provocative tests.
77
Treatment
. Small benign lesions can be enucleated.
. Malignant lesions are treated by pancreatic resection (distal
pancreatectomy or Whipple’s operation). Stropozotocin is an
effective chemotherapeutic agent.
Prognosis
. The median survival for malignant tumours is 5 years after
curative resection.
. The median disease-free survival falls to 4 years after palliative
resection.
24 Gastrinoma
Pathology
. A non-b-islet-cell tumour of the pancreas is the commonest
cause.
. Around 60% of tumours are malignant.
. Around 65% of cases occur in the pancreas and 35% in the
duodenum.
. Gastrinoma is associated with MEN I.
Clinical features
. Causes hypergastrinaemia and hypersecretion of gastric acid
(atypical peptic ulceration, Zollinger–Ellison syndrome).
Investigations
. Serum gastrin and gastric acid output.
. Secretin test.
. Localisation with arteriography, upper gastrointestinal series,
CT, selective venous sampling and/or MRI.
Treatment
. Surgical resection of well-localised tumours. Only 20% of
tumours are resectable.
. Medical treatment with omeprazole, lansoprazole, somatostatin
analogues and/or streptozotocin.
. Total gastrectomy is a recognised treatment modality.
79
25 Malignant
phaeochromocytoma
Pathology
. Arises from the neural crest-derived chromaffin tissue.
. Accounts for approximately 7% of phaeochromocytomas.
. Around 90% of tumours are found in the adrenal medulla.
. Secretes excess amounts of adrenaline and noradrenaline.
Clinical features
. Usually presents with general symptoms such as hypertension,
palpitations, headache, anxiety, nausea and vomiting, and local
symptoms depending upon location.
Investigations
. Diagnosis is based on elevated serum and urinary catecholamines
(VMA, adrenaline and noradrenaline).
. Neuron-specific enolase is a useful marker.
. Localisation using [131I]-MIBG (metiodobenzylguanidine) scan
(95% accuracy), CT and/or MRI.
. Vena cava sampling is occasionally performed.
80
Malignant phaeochromocytoma 81
Treatment
. Pre-operative preparation includes a-blockade (3 weeks of
phenoxybenzamine), b1-blockade and correction of vascular
volume.
. Surgical removal of tumour.
. Embolisation.
. a- and b-blockers for symptom control.
. [131I]-MIBG scan and chemotherapy (cyclophosphamide,
vincristine and dacarbazine).
Prognosis
. The 5-year survival rate is 40%.
26 Adrenocortical
malignancy
Epidemiology
. Women are more commonly affected.
. The peak incidence occurs during the fourth decade.
Pathology
. Tumours may be non-functioning (compressing and invading
surrounding structures) or functioning, causing Cushing’s syn-
drome (50%), virilisation (30%), feminisation (12%) or Conn’s
syndrome (very rare).
. Around 40% of patients have metastases at presentation.
Investigations
. Biochemical measurement (serum cortisol, ACTH, steroid
suppression tests, etc.).
. CT, USS, MRI, IVU, angiography and/or selective venous
sampling.
. CT-guided biopsy.
Treatment
. Adrenalectomy (lateral or anterior approach).
82
Adrenocortical malignancy 83
. Chemotherapy (mitotane, streptozotocin, 5-FU, doxorubicin

and/or cisplatin).
Prognosis
27 Carcinoid
tumours
Epidemiology
. Carcinoid tumours arise from amine precursor uptake
decarboxylase (APUD) cells and secrete serotonin.
Pathology
. Around 75% of the tumours occur in the mid-gut with 45% in
the appendix.
Clinical features
. Carcinoids present with local symptoms (appendicitis or bowel
obstruction) or symptoms of the carcinoid syndrome (found in
9% of cases).
. Right cardiac complications occur in 50% of cases.
Investigations
. The investigation of choice is 24-hourly urinary 5-hydroxyindole
acetic acid (5-HIAA) measurement.
. Barium studies, colonoscopy, CT, MRI, USS and/or laparoscopy.
84
Carcinoid tumours 85
Management
. Surgery.
– For non-metastatic primary tumours or obstructive intestinal
lesions.
– Appendix: appendicectomy for lesions < 2 cm in diameter
and right hemicolectomy for lesions > 2 cm in diameter.
– Stomach and duodenum: local excision for tumours < 1 cm
in diameter.
– Small bowel: small bowel resection with mesentery.
– Rectum: local excision if lesion is < 2 cm in diameter and
excision of rectum if lesion is > 2 cm in diameter.
– Solitary metastasis in liver can be treated by hepatic resection.
. Somatostatin analogs such as octreotide and lanreotide for the
carcinoid syndrome.
. Chemotherapy.
– The role is not clearly defined.
– It may be given for metastatic disease or as an adjuvant to
surgery and/or radiotherapy.
– The response rate is 33%. No survival benefit has been
demonstrated.
– 5-FU, streptozotocin, doxorubicin and cyclophosphamide
are usually used.
. Embolisation for hepatic metastases.
. Interferons.
. Other drugs include histamine antagonists and 5-HT antagonists.
. Other treatments:
– brachytherapy
– photodynamic therapy
– endoscopic mucosectomy
– surgical bypass (Kirschner operation)
– electrocoagulation
– ethanol injection
– radionuclide ablation.
Prognosis
28 Thyroid cancer
Epidemiology
. The female:male ratio is 2.5:1.
Aetiology
. Radiation (accounts for 10% of cases).
. Genetic factors (medullary thyroid carcinoma, MTC).
. Pre-existing benign conditions (e.g. Hashimoto’s thyroiditis,
multinodular and endemic goitres).
Pathology
. Papillary tumours:
– account for 70% of cases
– are usually low grade
– the incidence of multifocal and bilateral disease is 80%
– the regional lymph nodes are involved in 50% of cases.
. Follicular tumours:
– lymph-node metastases occur in 5% of cases
– vascular invasion is a poor prognostic indicator
– Hürthle-cell carcinoma is a cytological variant of follicular
carcinoma.
. Medullary tumours:
– arise in parafollicular C-cells
– there is an association with MEN syndrome (type IIa)
86
Thyroid cancer 87
– calcitonin is a useful serum marker

– the tumours may secrete ACTH and prostaglandins.
. Anaplastic carcinoma:
– accounts for 7% of cases
– occurs predominantly in the elderly and carries a poor
prognosis.
. Lymphoma:
– accounts for 1% of thyroid tumours
– is usually of the non-Hodgkin’s type
– poor prognostic indicators include spread beyond the cervi-
cal nodes, necrosis and vascular invasion.
. Incidental pathological findings in a thyroidectomy specimen
excised for benign disease.
. Discrete thyroid nodule. Around 5% of all solitary nodules are
malignant.
. Recently enlarging, multinodular goitre.
. Cervical lymphadenopathy.
. Neck mass with pressure symptoms.
. Voice change.
. Distant metastases.
Investigations
. Fine-needle aspiration cytology. This is the most useful inves-
tigation.
. Thyroid function tests.
. Ultrasonography.
. Core biopsy may be considered in some cases.
. CXR.
. CT and MRI may be useful for assessing the extent of disease.
. Radioactive iodine scan following total thyroidectomy.
. Serum calcitonin for medullary tumours.
. Serum thyroglobulin and its antibodies to screen for recurrence
after complete thyroidectomy.
Management
. Total thyroidectomy and removal of involved lymph nodes.
The recurrent laryngeal nerve should be identified and pre-
served. Attempts should also be made to preserve the para-
thyroids. Unilateral lobectomy is adequate for solitary tumours
less than 1 cm in diameter. The sentinel-node biopsy may be
used to assess the nodal status.
. Thyroxine is used to suppress thyroid-stimulating hormone
(TSH) activity.
. Radioactive iodine ( [131I] ) is used for follicular carcinoma,
advanced papillary carcinoma (stages II to IV) and metastatic
disease.
. External beam radiation is used for inadequately excised pap-
illary, follicular, medullary and Hürthle-cell carcinomas.
. External radiation and chemotherapy are used to control ana-
plastic carcinoma.
. Lymphoma is treated by radiotherapy. Chemotherapy is
indicated if there is retrosternal or distant spread.
Follow-up
. Physical examination.
. Thyroid function tests.
. Serum thyroglobulin and its antibody.
. Radioactive iodine ([131I]) scan.
. Serum calcitonin (medullary carcinoma).
Prognosis
Prognostic factors include the histological type, the tumour’s size
and degree of differentiation, nodal spread, distant metastases,
multifocality, the patient’s age (age above 45 years is a poor prog-
nostic factor) and whether the tumour is genetically determined.
Thyroid cancer 89
. Papillary carcinoma:
– low-risk category tumours have a 10-year survival rate of
97%
– high-risk category tumours have a 10-year survival rate of
85%.
. Follicular carcinoma:
– low-risk category tumours have a 10-year survival rate of
89%
– high-risk category tumours have a 10-year survival rate of
73%.
. Medullary carcinoma:
– the 5- and 10-year survival rates are 69% and 65%, respect-
ively
– hereditary cases are associated with a worse clinical outcome
than sporadic cases.
. Anaplastic carcinoma:
– the 3-year survival rate is 3%.
Screening for MTC

. The gene responsible for MTC and MEN II (the RET proto-
oncogene) has been localised to chromosome 10q11.2.
. First-degree relatives of patients with MTC should be screened
for MTC and other endocrine neoplasms such as parathyroid
adenoma and phaeochromocytoma.
. Screening for MTC includes physical examination, serum
calcitonin, PTH, VMA, cytogenetics and biopsy.
. Medullary thyroid hyperplasia is a pre-malignant condition
and is a recognised indication for prophylactic total thyroid-
ectomy.
29 Parathyroid
carcinoma
Epidemiology
. This accounts for 1% of all cases of primary hyperthyroidism.
. It is equally common in men and women.
. It is a rare tumour.
Pathology
. Histological diagnosis is often difficult.
. Chief cells predominate.
. Flow cytometric analysis of DNA aids the diagnosis.
Presentation
. Symptoms of hypercalcaemia, including renal stones (56% of
cases) and bone involvement (90%).
. Acute pancreatitis (12%).
. Neck mass (45%).
Investigations
. Serum calcium and parathyroid hormone (levels are higher
than in benign disease).
. FNAC.
. Localisation with CT, MRI or thallium–technetium scanning.
90
Parathyroid carcinoma 91
Treatment
. Treatment of hypercalcaemia (with rehydration and bisphos-
phonates).
. Removal of the tumour en masse with the thyroid lobe, lymph
nodes and ipsilateral isthmus.
. The nerve may be sacrificed if it is involved.
. Most patients require oral calcium and vitamin D.
Prognosis
. Frequent measurement of serum calcium and PTH levels is
required during follow-up.
. The 5-year local recurrence rate is 45%.
30 Soft tissue
sarcoma (STS)
Epidemiology
. This accounts for 1% of adult cancers and 15% of paediatric
cancers.
. The sex distribution is approximately equal.
. Around 43% of cases arise in the lower extremity, 16% in the
upper extremity, 13% in the visceral organs, 12% in the
retroperitoneum, 10% in the trunk, 5% in the head and neck
and 3% in the chest.
Aetiology
. The aetiology is unknown in most cases.
. The risk factors include genetic disorders (Li-Fraumeni syndrome,
hereditary retinoblastoma, neurofibromatosis and Gardner’s
syndrome), radiation, lymphoedema, thorium oxide (angio-
sarcoma) and vinyl chloride.
Pathology
. The likelihood of metastasising is greater than 50% for high-
grade sarcomas, compared with less than 15% for low-grade
sarcomas.
. Immunohistochemical analysis (utilising a panel of antibodies)
is used to specify sarcoma type.
. Lymph-node metastases occur in less than 35% of cases.
92
Soft tissue sarcoma (STS) 93
Clinical features
. Extremity sarcomas present as a painless mass. The presence of
pain indicates a poor prognosis. In general, soft tissue masses
which are large in size (> 5 cm in diameter), painful, located
deep to superficial fascia and/or increasing rapidly in size
should raise the suspicion of sarcoma.
. Retroperitoneal sarcoma patients present with abdominal
mass, abdominal pain, neurological symptoms or bowel ob-
struction.
. Other symptoms include abnormal uterine bleeding (uterine
sarcoma), haematuria (bladder sarcoma) and nasal bleeding/
obstruction (nasal and paranasal sarcomas).
Diagnosis
. Core biopsy is more informative than FNAC.
. CT and/or MRI to assess the extent of disease.
. CXR.
Treatment
. Extremity and trunk. Limb-sparing surgery is an important
principle of treatment.
– Low-grade tumours of the extremity and trunk are treated by
wide local resection. External radiotherapy is indicated for
large (> 5 cm in diameter) or incompletely excised tumours.
– High-grade tumours are treated by wide local resection
followed by adjuvant radiotherapy (brachytherapy/external
radiotherapy). Chemotherapy may be considered for large
high-grade sarcomas (> 10 cm in diameter). Lung metastases
should be excluded prior to treatment.
. Retroperitoneal and visceral sarcomas are treated by surgical
resection. Incompletely excised tumours and large (> 10 cm in
diameter) high-grade tumours should be considered for radio-
therapy and chemotherapy.
. Gastrointestinal sarcomas may cause bleeding, perforation,

ulceration and/or obstruction. These complications require
appropriate surgical treatment.
. A minimal 2 cm margin of normal tissue is required for
adequate excision.
Investigations
. Excisional biopsy for superficial tumours < 3 cm in diameter.
. Incisional biopsy or core biopsy (which has limitations) for
large and deeply seated tumours.
. LFTs, serum U&Es and FBC.
. MRI scan (superior to CT).
. CXR.
. Thoracic CT if CXR suggests the presence of metastases.
. USS or CT of liver.
Notes
. Pulmonary metastases can be excised surgically so long as there
is good local control of the primary tumour and there is no
evidence of extrapulmonary metastases. The 5-year survival
rate is 26% following resection.
. Metastatic sarcoma can be treated by chemotherapy (e.g.
doxorubicin and ifosfamide), with response rates approaching
35%.
. Local recurrence is treated by surgical excision and radio-
therapy.
Follow-up
. Patients with high-grade tumours of the extremity and trunk
should be examined and have a CXR every 3 months for the
first 3 years, twice a year for the next 2 years and annually
thereafter. A thoracic CT may be performed.
Soft tissue sarcoma (STS) 95
. Patients with visceral and retroperitoneal sarcomas should also

have an abdominal CT during follow-up.
Prognosis
. Depends upon the size, grade and site of the tumour, the
adequacy of excision and the histopathological type.
. The 5-year survival rate is 25% for retroperitoneal sarcoma
and 80% for extremity sarcoma.
31 Kaposi’s
sarcoma
Epidemiology
. Kaposi’s sarcoma (KS) is relatively common among elderly
men (over 50 years) of Mediterranean origin, Ashkenasi Jews
and individuals infected with herpes simplex virus (HSV).
. It is the commonest tumour associated with AIDS.
Aetiology
– HSV infection
– cytomegalovirus infection
– immunosuppression.
Pathology
. The tumour is derived from vascular or lymphatic endothelium.
Clinical features
. Pigmented, non-blanching skin lesions. The lesions are initially
red/blue and flat, and later become purple, raised and coalesc-
ent. There may be associated bruising and/or lymphoedema.
. Mucocutaneous lesions. Intra-oral lesions account for 15% of
clinical presentations.
96
Kaposi’s sarcoma 97
. Gastrointestinal KS may cause GI bleeding, perforation, intus-

susception and/or obstruction.
. Pulmonary KS may cause dyspnoea, haemoptysis and/or cough.
Investigations
. Surgical biopsy.
. HIV testing.
. CD4 count.
Treatment
. Radiotherapy for lesions on the face, trunk, limbs and penis.
The response rate is 60%.
. Intralesional vinblastine is a recognised treatment modality.
. Camouflaging cream.
. Systemic bleomycin, vincristine and steroids for aggressive skin
lesions and symptomatic visceral and pulmonary lesions.
. Zidovudine for HIV-infected individuals.
. Surgery for the complications of visceral lesions.
Prognosis
. This depends on the CD4 count, performance status and the
presence of multiple lesions.
. The median survival is 1.5 years from the time of diagnosis.
32 Osteosarcoma
Epidemiology
. This accounts for 3.5% of childhood malignancies.
. It is the commonest primary malignancy of bone.
. The peak incidence occurs in the second decade.
. The male:female ratio is 1.5:1.
Aetiology
. Ionising radiation.
. Li-Fraumeni syndrome.
. Paget’s disease of bone.
. Tumour suppressor genes (e.g. p53) and oncogenes (c-erb B-2,
c-fos, MDM2, SAS and CDK4).
Pathology
. The tumour usually arises in the epiphysis around the knee
(lower femur and upper tibia).
Clinical features
. Pain and swelling around the knee. The swelling is usually
tender and warm. There may be limitation of limb movement.
. The plain radiograph usually shows a destructive lesion in the
metaphyseal region with new bone formation. There may be
elevation of the periosteum (Codman’s triangle).
98
Osteosarcoma 99
Investigations
. CT or MRI of the tumour.
. CXR, serum alkaline phosphatase (reflects disease activity),
CT of thorax and radioisotope bone scan.
Management
. This is based on a multi-disciplinary approach involving sur-
gery and chemotherapy.
– Chemotherapy can be given pre-operatively (neoadjuvant)
and/or post-operatively (adjuvant), and has been shown to
improve survival.
– Chemotherapeutic agents used include high-dose metho-
trexate, cisplatin, doxorubicin, etoposide and ifosfamide.
– Conservative limb-sparing surgery.
– Limb-salvage procedures include allograft replacement and
endoprosthetic reconstruction.
Prognosis
. The overall cure rate is 60%.
. Favourable prognostic factors include older age (> 15 years),
smaller tumour volume, low histological grade, tibial origin,
histological response to chemotherapy and the absence of
distant metastases.
. Pulmonary metastases can be resected surgically, with a 3-year
survival rate approaching 50%.
33 Cutaneous
melanoma
Epidemiology
. The incidence ranges from 0.7 per 100 000 (in black Americans)
to 40 per 100 000 (in white Australians) per annum.
. Malignant melanoma accounts for 2.5% of all newly diag-
nosed cancers.
. The incidence is rising (there has been a 50% rise in the last
decade).
. The peak incidence occurs during the fifth decade.
Aetiology
– family history of melanoma
– history of multiple atypical naevi
– the presence of atypical or numerous naevi
– inability to tan (fair skin)
– excessive exposure to ultraviolet radiation
– immunosuppression
– genetic factors such as p53 and CDKN2A gene mutations.
Classification
. Superficial spreading melanoma accounts for 70% of cases.
. Nodular melanoma accounts for 15% of cases.
. Lentigo maligna is uncommon and carries an excellent prog-
nosis.
100
Cutaneous melanoma 101
. Acral lentiginous melanoma represents 10% of all melanomas.

. Amelanotic melanoma. This subtype is difficult to diagnose
clinically due to the lack of visual pigmentation. Dermatoscopy
may aid the diagnosis.
Clinical staging system

. Stage 0: Tis, N0, M0
The melanoma is in situ, meaning that it involves the epidermis
but has not spread to the dermis (lower layer). This is also
called Clark level I.
. Stage IA: T1a, N0, M0
The melanoma is less than 1.0 mm in thickness and Clark level
II or III. It is not ulcerated, appears to be localised in the skin,
and has not been found in lymph nodes or distant organs.
. Stage IB: T1b or T2a, N0, M0
The melanoma is less than 1.0 mm in thickness and is ulcerated
or Clark level IV or V, or it is between 1.01 and 2.0 mm and is
not ulcerated. It appears to be localised in the skin and has not
been found in lymph nodes or distant organs.
. Stage IIA: T2b or T3a, N0, M0
The melanoma is between 1.01 and 2.0 mm in thickness and is
ulcerated, or it is between 2.01 and 4.0 mm and is not ulcerated.
It appears to be localised in the skin and has not been found in
lymph nodes or distant organs.
. Stage IIB: T3b or T4a, N0, M0
The melanoma is between 2.01 and 4.0 mm in thickness and is
ulcerated, or it is thicker than 4.0 mm and is not ulcerated. It
appears to be localised in the skin and has not been found in
lymph nodes or distant organs.
. Stage IIC: T4b, N0, M0
The melanoma is thicker than 4.0 mm and is ulcerated. It appears
to be localised in the skin and has not been found in lymph
nodes or distant organs.
. Stage III: Any T, N1–3, M0
The melanoma has spread to lymph nodes near the affected skin
area. There is no distant spread. The thickness of the melanoma is
not a factor, although it is usually thick in people with stage III

melanoma.
. Stage IV: Any T, Any N, Any M1
The melanoma has spread beyond the original area of skin and
nearby lymph nodes to other organs, such as the lung, liver or
brain, or to distant areas of the skin or lymph nodes. Neither
the lymph node status nor thickness is considered, but in
general, the melanoma is thick and has spread to lymph nodes.
Investigations
. Incisional or excisional biopsy. The latter is preferable if possible.
. FNAC of masses suggestive of metastases (e.g. regional lymph
nodes).
. Staging investigations include CXR, liver USS, CT, bone scan
and serum lactate dehydrogenase (LDH).
Treatment
. Primary melanoma is treated by adequate local excision. The
defect is closed primarily or using skin grafts and local flaps.
The clear margins should be 1 cm for melanoma thickness of
< 2 mm and 2–3 cm for melanoma thickness of > 2 mm.
. Lymph nodes.
– Elective lymph node dissection is performed if the primary
melanoma is > 1.5 mm thick and/or there is lymph node
involvement.
– Alternatively, a regional lymph node dissection is performed
if the sentinel node is positive for metastatic disease. The
sentinel node can be accurately identified (95%) using radio-
active isotopes and vital blue dye, and provides an accurate
assessment of the regional lymph nodes.
. High-dose interferon-a seems to improve survival in patients
with high-risk melanoma.
. Locally advanced/recurrent melanoma is treated by hyper-
thermic isolated limb perfusion (e.g. with melphalan), with a
remission rate of 40%.
Cutaneous melanoma 103
. Distant metastases.
– Systemic chemotherapy using dacarbazine (20–25% response
rate).
– Solitary or limited numbers of metastases in the brain, intestine
or lungs can be resected with prolongation of survival.
– Immunotherapy (e.g. with interferon-a) has a 15–20% re-
sponse rate. Vaccination, anti-tumour vaccines, monoclonal
antibodies and high-dose interleukin-2 (IL-2) are still under
investigation.
– Radiotherapy for palliation of inoperable brain, lymph node
and bone metastases.
Follow-up
. Stage IA patients should be reviewed 6-monthly for 2 years,
and then yearly.
. Stage IB and IIA patients should be reviewed 4-monthly for
3 years, and then yearly.
. Stage IIB and III patients should be reviewed 4-monthly for
5 years, and then yearly.
. Patients should be educated in self-examination.
Prognosis
. This depends upon tumour stage, thickness and the presence of
ulceration, the patient’s age and sex, the primary lesion site and
the growth pattern.
. The 5-year survival rate is 90–95% for stage I; 85% for stage
IIA; 73% for stage IIB; 53% for stage IIC; 45% for stage III;
10% for stage IV.
34 Non-
melanocytic skin
cancer
Epidemiology
. This is the commonest cancer among Caucasians in the UK and
the USA.
. Its incidence is increasing.
. The incidence is slightly higher in men (especially above the age
of 70 years).
Aetiology
. Actinic radiation.
. Chronic skin ulcers and sinuses.
. Immunosuppression.
. Genetic predisposition, including xeroderma pigmentosum,
multiple familial self-healing squamous-cell carcinoma and
Gorlin–Goltz syndrome (basal-cell carcinoma).
. Bowen’s disease predisposes to squamous-cell carcinoma.
Pathology
. Basal-cell carcinoma (BCC) usually invades locally. Regional
lymph node involvement is extremely rare.
. Squamous-cell carcinoma (SCC) systemic spread occurs in 2%
of cases.
104
Non-melanocytic skin cancer 105
Clinical features
. A skin ulcer. The ulcer margins may be rolled (in SCC) or pearly
and everted (in BCC). Surface telangiectasia may be present (in
BCC).
. A skin nodule or cystic lesion.
. The skin lesion is occasionally pigmented.
. Regional lymphadenopathy (in SCC).
Investigations
. Excisional biopsy.
. Incisional biopsy.
. Shaving biopsy.
Treatment
. Adequate surgical excision with a minimal margin of 4 mm for
BCC and 1 cm for SCC. The surgical defect can be closed
primarily or using a skin graft, a local flap or a myocutaneous
flap (conventional or free transfer).
. Radiotherapy is an effective treatment modality.
. Regional lymph node dissection or radiotherapy is used for
involved nodes.
. Other treatment modalities include cryosurgery, laser therapy,
curettage or electro-desiccation.
Prognosis
. The 5-year survival rate is 98% for SCC and 100% for BCC.
. Death from BCC is extremely rare.
. The 5-year incidence of further BCC lesions is 40%.
35 Ovarian cancer
Epidemiology
. This accounts for 25% of all gynaecological malignancies.
. The incidence is 22.8 per 100 000 per annum in the UK.
Aetiology
– late menopause
– family history of ovarian, endometrial, breast or bowel
cancer
– nulliparity
– late first pregnancy
– use of peritoneal talc
– BRCA-1 gene.
Pathology
. Epithelial carcinoma accounts for 90% of cases.
. Exfoliation through the peritoneal cavity and lymphatic spread
are the commonest modes of dissemination.
Clinical features
. Irregular periods.
. Abnormal vaginal bleeding.
. Abdominal pain (50% of cases).
106
Ovarian cancer 107
. Urinary or bowel symptoms.

. Ascites.
. Abdominal distension.
. Dyspareunia and anorexia.
. Pelvic mass.
. Constitutional symptoms (50% of cases).
Investigations
. Abdomino-pelvic US, CT or MRI scan.
. Serum CA125, a-fetoprotein (AFP) and human chorionic gon-
adotrophin (HCG).
. CXR, IVU and barium enema.
. Laparoscopy.
. Laparotomy/biopsies.
Treatment
. Early-stage disease confined to the ovary can be treated by total
abdominal hysterectomy and bilateral salpingo-oophorectomy
(BSO), infracolic omentectomy and surgical staging. Systemic
chemotherapy is required for poorly-differentiated (grade 3)
tumours.
. Advanced-stage disease is treated by debulking surgery that
aims to reduce the disease to < 1.5 cm tumour followed by
chemotherapy (cisplatinum and paclitaxel for 6 cycles).
. Recurrent disease is treated by chemotherapy (e.g. with
liposomal doxorubicin or topotecan) and/or radiotherapy.
. Germ-cell tumours in the young are treated by chemotherapy
following surgical staging.
Prognosis
. The 5-year survival rate is 88% for stage I lesions (lesions
confined to the ovary), 70% for stage II lesions (lesions
extending to the pelvis only) and 20% for advanced disease.
Future directions
. The role of angiogenesis inhibitors (angiostatin, endostatin,
thalidomide and EGFR antagonists), COX-2 inhibitors,
Herceptin in patients with HER2-positive tumours (10%),
photodynamic therapy and immune modulation is currently
being evaluated in patients with advanced and recurrent dis-
ease.
. Serum proteomics using mass spectrometry seems to be prom-
ising in the early detection of ovarian cancer.
36 Endometrial
carcinoma
Epidemiology
. Endometrial carcinoma is one of the commonest gynaecolog-
ical malignancy.
. Its incidence has been increasing.
. The median age of onset is 60 years.
. Around 20% of cases occur before the menopause.
. The incidence is low in Nigeria (0.6 per 100 000 women) and
high in the UK (18.7 per 100 000 women).
Aetiology
– obesity
– late menopause
– diabetes mellitus
– nulliparity
– unopposed oestrogen exposure
– tamoxifen therapy.
Pathology
. Adenocarcinoma is the commonest type (90% of cases).
. Other histopathological types include adenoacanthoma, adeno-
squamous and leiomyosarcoma.
. Direct extension is the commonest mode of spread.
109
Clinical features
. Abnormal vaginal bleeding (90% of cases).
. Abnormal cervical smear cytology.
. Symptoms and signs of metastases.
Investigations
. Cervical smear cytology and endocervical curettage.
. Endometrial biopsy.
. Dilatation and curettage.
. Hysteroscopy.
. Staging investigations include FBC, LFTs, U&Es, CXR, IVP,
abdomino-pelvic CT or MRI and/or bone scan (if indicated).
Staging (FIGO)
. Stage I:
– IA – tumour limited to the endometrium
– IB – invasion of < 50% of myometrium
– IC – invasion of > 50% of myometrium.
. Stage II:
– IIA – endocervical glandular involvement only
– IIB – cervical stromal invasion.
. Stage III:
– IIIA – tumour invades serosa/positive peritoneal washings
– IIIB – vaginal metastases
– IIIC – metastases to pelvic/aortic lymph nodes.
. Stage IV:
– IVA – invasion of bowel/bladder mucosa
– IVB – distant metastases.
Endometrial carcinoma 111
Treatment
. Stage I and II disease is treated by total abdominal hyster-
ectomy and bilateral salpingo-oophorectomy (BSO). Pelvic
and para-aortic lymph nodes are sampled. Radiotherapy is
indicated for poorly differentiated carcinoma (grade III).
. Stage IC, IIA and IIB lesions. Large stage I lesions may be treated
by pre-operative radiotherapy followed by hysterectomy and
BSO 6 weeks later.
. Advanced and recurrent lesions are treated by a combination of
surgery, radiotherapy, chemotherapy (doxorubicin) and hor-
monal manipulation.
. Hormonal manipulation includes megestrol acetate (80 mg
twice a day), medroxyprogesterone acetate (50 mg three times
a day) and anti-oestrogens.
Prognosis
30% for stage III and 10% for stage IV.
37 Cervical
cancer
Epidemiology
. Cervical cancer is the second cause of female malignancy
worldwide.
. A total of 13 500 new cases are diagnosed in the USA every year.
. The average age of onset is 45 years.
. The incidence is declining.
Aetiology
. Risk factors include cervical intra-epithelial neoplasia (CIN),
young age at first intercourse, high parity, low socio-economic
status, human papilloma virus (HPV) infection (types 16, 18,
31, 33 and 35), smoking, venereal infections and multiple
sexual partners.
Pathology
. Squamous-cell carcinoma (SCC) accounts for 80% of cases.
. Adenocarcinoma and adenosquamous lesions account for
20% of cases.
Clinical features
. Vaginal discharge.
112
Cervical cancer 113
. Abnormal vaginal bleeding (post-coital, post-menopausal or

irregular) is present in 85% of cases.
. Abnormal routine cervical smear.
. The cervical tumour may be ulcerative, necrotic, exophytic or
granular in appearance.
. Pelvic mass.
. Ureteric obstruction in advanced disease.
. Signs and symptoms of metastases (e.g. ascites and inguinal
lymphadenopathy).
Investigations
. Cervical cytology (Pap smear).
. Colposcopy plus biopsy or endocervical curettage or conisation.
. Cystoscopy and IVP.
. Sigmoidoscopy/barium enema.
. CXR (lung metastases are present in 5% of cases).
. Abdomino-pelvic CT or MRI scan.
. Bone scan.
. Combined vaginal and rectal examination under anaesthesia.
. FBC, serum U&Es and LFTs.
Staging (FIGO)
. Stage 0: carcinoma in situ.
. Stage I: carcinoma is confined to the cervix.
. Stage II: carcinoma extends beyond the cervix, but has not
extended to the pelvic wall or the lower third of the vagina.
. Stage III: carcinoma has extended to the pelvic wall or the
lower third of the vagina.
. Stage IVA: carcinoma has extended beyond the pelvic wall or
has involved the rectal/vesical mucosa clinically.
. Stage IVB: carcinoma is palliated by radiotherapy and chemo-
therapy.
Treatment
. CIN is managed by colposcopy and cryosurgery, CO2 laser,
electrocoagulation, loop electrodiathermy or cervical conisation.
CIN stage II may be cured by hysterectomy in patients who
have completed childbearing.
. Microinvasive disease (stage IA) can be treated by a cone biopsy
(with clear margins) or extrafascial abdominal hysterectomy.
. Stage IB and IIA tumours are treated by radical hysterectomy
with excision of parametrial tissue, vaginal cuff, lympha-
denectomy and sampling of the para-aortic nodes and/or radio-
therapy (external beam followed by intracavity radiation).
Surgery is superior to radiotherapy for adenocarcinoma.
. Stage IB, IIA and IIB lesions are treated by radiotherapy (external
beam followed by intracavity radiotherapy).
. Stage IVA carcinoma is treated by pelvic radiotherapy. Salvage
pelvic extenteration is reserved for partially responding tu-
mours.
. Recurrent disease is treated by chemotherapy (mitomycin C,
methotrexate, cyclophosphamide, bleomycin and cis-platinum),
pelvic extenteration and/or radiotherapy.
Prognosis
30% for stage III and 7% for stage IV lesions.
Screening
. All women, once they have become sexually active, should
undergo an annual physical examination and Papanicolaou
smear of the cervix.
. The false-negative rate for cervical cytology is 15% and the
false-positive rate is less than 1%.
Cervical cancer 115
Future prospects
ising in the early detection of cervical cancer.
. Cervical cancer vaccines based on HPV are likely to be avail-
able for clinical use within the next 5 years.
38 Vaginal cancer
Epidemiology
. Primary vaginal cancer accounts for 1.5% of all gynaecological
malignancies.
. The highest incidence occurs in the age range 50–70 years.
. Most lesions occur in the upper third of the vagina.
Aetiology
. Maternal ingestion of diethylstilboestrol during pregnancy
increases the incidence of vaginal clear-cell carcinoma in
daughters.
. Vaginal intra-epithelial neoplasia has a pre-malignant potential.
. Other risk factors include:
– vaginal pessaries
– venereal disease
– human papilloma virus (HPV) infection
– procidentia
– ulceration
– cervical cancer.
Pathology
. Squamous-cell carcinoma (SCC) accounts for 93% of cases and
adenocarcinoma accounts for 5% of cases.
. Embryonal rhabdomyosarcomas are seen in children.
116
Vaginal cancer 117
Clinical features
. Vaginal bleeding/discharge.
. Ulcerative/exophytic vaginal lesions.
. Urinary and gastrointestinal symptoms are occasionally seen.
. Regional lymphadenopathy (inguinal, femoral and obturator).
. Abnormal cervical smear.
Investigations
. Punch biopsy.
. Colposcopy and endometrial curettage.
. CXR.
. Cystoscopy and IVP.
. Abdomino-pelvic CT or MRI scanning.
. Sigmoidoscopy and/or barium enema.
Staging (FIGO)
. Stage I: tumour confined to the vaginal wall.
. Stage II: tumour has involved subvaginal tissue but has not
extended to the pelvic wall.
. Stage III: tumour has extended to the pelvic wall.
. Stage IV: tumour has extended beyond the pelvic wall or has
involved the rectal or vesicle mucosa.
Treatment
. Radiotherapy (external beam radiation or interstitial) is the
mainstay of management. The groins are included in the radio-
therapy field for tumours arising in the lower third of the
vagina.
. Surgery in the form of a wide local excision or total vagin-

ectomy is indicated for early vaginal cancer. Radical surgery
may entail hysterectomy and pelvic lymphadenopathy.
. Psychological counselling is essential prior to vaginectomy.
. A neovagina may be reconstructed using a split-thickness skin
graft.
. Surgery is indicated for recurrent tumours following radio-
therapy.
Prognosis
33% for stage III and 7% for stage IV tumours.
. Around 10% of patients develop significant bowel and bladder
side-effects following radiotherapy.
39 Vulval cancer
Epidemiology
. Vulval cancer accounts for 4% of all gynaecological cancers.
. The incidence is highest during the seventh decade of life.
Aetiology
. Risk factors include immunosuppression, vulval dystrophy and
human papilloma virus infection.
Pathology
. Squamous-cell carcinoma accounts for 85% of cases.
. Melanoma accounts for 5% of cases.
Clinical features
. Vulval pruritus/pain.
. Vulval ulcer/mass.
. Inguinal lymphadenopathy.
Investigations
. Surgical biopsy.
. FNAC of regional lymph nodes (if enlarged).
. Abdomino-pelvic CT or MRI for staging.
119
Treatment
. Carcinoma in situ and microinvasive disease are managed by
local vulval excision with a clear margin of 1 cm.
. Lateral cancers less than 2 cm in diameter are managed by
vulvectomy (with a 2 cm clear margin) and ipsilateral lymph
node dissection. A contralateral lymph node dissection is
recommended if the ipsilateral nodes are involved.
. Bilateral inguinal lymph node dissection is indicated for vulval
cancer involving the clitoris.
. Pelvic lymphadenectomy is recommended for lesions over 4 cm
in diameter.
. The terminal urethra can be excised in order to achieve ad-
equate local excision.
. Butterfly or triple incision is used for vulvectomy and inguinal
node dissection. Skin flaps are created to relieve tension. Deep
vein thrombosis (DVT) and antimicrobial prophylaxis is es-
sential.
. Compression stockings and lymphoedema play an important
role after inguinal node dissection (the incidence of lymph-
oedema is 60%).
. Radiotherapy can be given pre-operatively to render large
lesions operable. Other indications include inadequate margins
and recurrent disease.
. Chemotherapy (bleomycin and methotrexate) has a minor
role.
40 Renal
adenocarcinoma
Epidemiology
. This accounts for 3% of all adult cancers.
Aetiology
. Risk factors include Hippel–Lindau syndrome, smoking, ex-
posure to cadmium, and polycystic kidneys of patients on renal
dialysis.
Pathology
. Polygonal or round cells with abundant cytoplasm are charac-
teristic.
. Haematogenous spread is the principal mode of metastasis.
Clinical features
. The main symptoms are loin pain (40% of cases), haematuria
(40%), abdominal mass (25%) and weight loss (35%).
. Other features include varicocoele, hypercalcaemia, poly-
cythaemia, hypertension and night sweating.
121
Investigations
. Urine microscopy and culture, FBC, serum, U&Es, serum
calcium and CXR.
. IVU.
. Ultrasonography.
. CT or MRI scanning.
. Bone scan.
Treatment
. Total nephrectomy with perinephric fat and Gerota’s fascia
after early control and division of renal vessels through an
anterior approach. Lymph node dissection has a low yield of
metastasis (3%).
. Partial nephrectomy for small cortical tumours and bilateral
lesions.
. Palliation of metastatic disease includes analgesia, Provera
(100 mg three times a day), radiotherapy to bone secondaries
and radiological embolisation for intractable haematuria.
. Interferon-a is indicated for selected patients with metastatic
disease (response rate is around 15%). It prolongs life by 5
months.
. The role of interleukin-2 (IL-2), gene therapy and immuno-
therapy is currently under investigation.
Prognosis
. The 5-year survival rate is 70% if the tumour is confined within
the capsule, 45% if the tumour has breached Gerota’s fascia
and 30% if there is regional lymph node involvement.
41 Wilms’ tumour
Epidemiology
. This accounts for 6% of all childhood malignancies.
. The peak incidence occurs between 3 and 4 years of age.
Pathology
. It may be multifocal and bilateral (5%).
. Mesodermal, mesonephric and metanephric origins have been
proposed for this tumour.
Clinical features
. Abdominal mass, anorexia, haematuria and/or hypertension.
. Associated congenital abnormalities include aniridia, hemi-
hypertrophy, cryptorchidism and Beckwith’s syndrome.
Investigations
. Abdominal USS or CT.
. CXR.
. Renogram.
. Doppler examination of the renal vein and inferior vena cava.
123
Staging
. Stage I: tumour is confined to the kidney and completely
excised.
. Stage II: tumour extends beyond the renal capsule but is com-
pletely excised.
. Stage III: tumour is inoperable, incompletely excised or rup-
tured diffusely during removal.
. Stage IV: distant metastases are present.
. Stage V: tumour is bilateral.
Treatment
. Surgical debulking of the tumour should be undertaken if
possible (nephrectomy).
. Radiotherapy and chemotherapy (vincristine and actinomycin
D for stages I and II; vincristine, actinomycin and adriamycin
for stages III, IV and V).
. Chemotherapy is given pre-operatively in stages IV and V.
. Radiotherapy is indicated in stages III, IV and V.
Prognosis
. The 5-year survival rate is 95% for stages I and II, 82% for
stage III, 60% for stage IV and 67% for stage V.
42 Urothelial
carcinoma
Epidemiology
. The incidence is 17 per 100 000 per annum.
. It is more common in industrialised countries.
Aetiology
. Risk factors include smoking and occupational hazards (rub-
ber, aniline dye and plastics industries, tyre destruction and
cable production).
. Genetic abnormalities and oncogenes (ras and C-myc) have
been implicated.
. Balkan nephropathy.
. Drugs (e.g. phenacetin and cyclophosphamide).
Pathology
. Around 95% of lesions affect the bladder.
. Transitional-cell carcinomas (TCC) can be subdivided into
carcinoma in situ (CIS), superficial and deep disease (involving
muscle).
125
Clinical features
. Haematuria is the commonest symptom.
. Other symptoms include loin pain, urinary tract infection,
weight loss, back pain and jaundice.
. Signs include renal and pelvic masses.
Investigations
. Urine microscopy and culture.
. Urine cytology and proteomics (NMP22).
. IVU and flexible cystoscopy.
. Diagnostic cystoscopy (under general anaesthetic) and biopsy.
. USS, CT or MRI.
. Other investigations include LFTs, bone scan, CXR and
laparoscopic sampling of pelvic lymph nodes.

. TCC of the renal pelvis and ureter is treated by radical nephro-
ureterectomy if the tumour is poorly differentiated or has
invaded muscle. Segmental resection and end-to-end anasto-
mosis is suitable for well-differentiated and superficial tumours.
Urethroscopic laser therapy may be used to treat small tu-
mours. The median survival is 1 year for invasive tumours and
7 years for non-invasive tumours.
. Superficial TCC is treated by endoscopic transurethral resec-
tion and surveillance.
. Intravesical chemotherapy (mitomycin and epirubicin) and
immunotherapy (BCG, bacille Calmette–Guérin) are suitable
for frequent and numerous recurrences.
. Radical cystectomy is considered for high-grade tumours with
lamina propria invasion, particularly if there is coexistent CIS.
. Primary CIS of the bladder is treated with intravesical mitomycin
and BCG in order to prevent aggressive disease. Recurrence or
failure to respond to the above treatment is an indication for
cystectomy.
Urothelial carcinoma 127
. Invasive TCC of the bladder.

– Patients with localised disease are offered radical cystectomy.
– A catheterisable or continent neobladder (e.g. hemi-Koch
pouch) is usually constructed after radical cystectomy.
– Radical cystectomy entails the removal of the regional lymph
nodes and prostate or uterus and anterior vaginal wall.
– Patients with metastases are treated palliatively. Palliation
includes radiotherapy, chemotherapy and/or cystectomy.
43 Prostatic
adenocarcinoma
Epidemiology
. The incidence is 75 per 100 000 per annum and is rising due to
ageing populations.
. Men have a 10% lifetime risk of developing the disease and a
3% risk of dying from it.
. The incidence is relatively high among American Negroes and
is low in Japan.
Aetiology
. Genetic and environmental factors (e.g. selenium deficiency)
have been implicated.
Pathology
. Most carcinomas arise in the peripheral zone.
. Haematogenous spread occurs predominantly to bone (scler-
otic lesions) and lymphatic spread occurs to pelvic nodes.
Clinical features
. Bladder outflow obstruction (urgency, frequency, nocturia,
urinary retention and hesitancy).
. Incidental findings in TURP specimens.
128
Prostatic adenocarcinoma 129
. Mass detected on digital rectal examination.

. Bony pain due to metastases.
. Haematuria.
Investigations
. Serum prostate-specific antigen (PSA) (normal range is < 4 ng/ml).
PSA is elevated in prostatic cancer, benign prostatic hyper-
plasia, prostatitis and urinary retention. It is useful for indicating
recurrence (after prostatectomy) and bony metastases.
. Transrectal ultrasonography and biopsy.
. Bone scan and pelvic CT and/or MRI may be indicated.

. Total prostatectomy.
– This is indicated for tumours that are confined to the prostate.
– The procedure cures all impalpable lesions confined to the
prostate (T1) and 35% of palpable tumours which appear to
be confined to the prostate (T2).
– The incidence of incontinence should be less than 5% and
that of impotence less than 20%. The incidence of impotence
is higher if a nerve-sparing technique is not adopted.
– The procedure can be performed laparoscopically with three-
dimensional viewing and magnification. This approach seems
to be associated with shorter hospitalisation times and lower
morbidity rates.
. Radiotherapy (external beam or interstitial).
– This is indicated for tumours that are confined to the pros-
tate (T1 and T2). The 5-year survival rate is approximately
65–70%.
– Radiotherapy achieves similar survival rates to surgery.
– It is also used to palliate bony pain due to metastases and
prostatic bleeding.
. Hormonal manipulation.
– This is indicated for metastatic disease. Around 80% of
tumours are sensitive to androgen deprivation.
– Modalities available include diethylstilboestrol (1 mg daily),

bicalutamide, cyproterone acetate, flutamide, luteinising
hormone-releasing hormone analogues (e.g. goserelin) and
orchidectomy (subcapsular or total). These modalities can
be used singly or in combination.
– The median survival for metastatic disease is 30 months.
. Bone metastases.
– Hormonal manipulation.
– External beam radiation.
– Strontium-89 chloride (systemic radionuclide therapy).
– Bisphosphonates.
Future prospects
ising in the early detection of prostate cancer. Early results
suggest that this test is more accurate than serum PSA.
. Computer-assisted endoscopic surgery is likely to become the
standard surgical treatment for early prostate cancer.
44 Testicular
cancer
Epidemiology
. The incidence is rising (e.g. 8 per 100 000 per year in Denmark).
. The peak incidence occurs between 20 and 34 years of age.
. The lifetime risk in Caucasians is 0.2%.
. The incidence is lower among Asians.
Aetiology
– cryptorchidism
– oestrogen exposure
– testicular torsion
– mumps
– orchitis
– testicular trauma, including open biopsy
– infertility
– early puberty
– lack of exercise
– orchidectomy
– low sperm counts
– elevated levels of follicle-stimulating hormone (FSH).
. It is likely that the FSH-driven over-stimulation of sperma-
togonia is the underlying mechanism for some of the above
factors.
131
Pathology
. Testicular germ-cell tumours account for 95% of cases.
. Histological subclasses include spermatocytic seminoma (classi-
cal and anaplastic), teratoma (differentiated, intermediate and
undifferentiated), embryonal carcinoma, choriocarcinoma (pure
and mixed) and yolk-sac tumour.
. Carcinoma in situ (CIS) is a universal precursor.
Clinical features
. Scrotal mass (painless in 75% of cases).
. Solid mass that cannot be distinguished from the testis.
. Secondary hydrocoele.
. Lymphadenopathy (abdominal or cervical).
. Gynaecomastia.
. Symptoms due to metastases (e.g. backache).
Investigations
. Ultrasonography.
. Serum tumour markers (a-fetoprotein, human chorionic gon-
adotrophin and lactate dehydrogenase). These remain import-
ant for diagnosis, and they have prognostic value and can be
used to monitor therapy and follow-up.
. Orchidectomy (via inguinal approach) for histological exam-
ination.
. Staging investigations including CXR, CT (thorax and abdomen),
lymphangiography, abdominal ultrasound and/or FNAC of
extra-scrotal masses. The false-negative rate for CT staging is
25%.
. PET scanning is useful for staging the disease in selected
patients.
Testicular cancer 133

. Stage I seminoma is treated by total orchidectomy plus adju-
vant chemotherapy (one or two courses of carboplatin) or
radiotherapy. The disease-free survival rate is 98–100%. Some
centres recommend long-term surveillance only and omit adju-
vant therapy.
. For stage I seminoma, adjuvant carboplatin chemotherapy
offers a similar disease-free survival rate to adjuvant radio-
therapy.
. Stage I non-seminoma is treated by total orchidectomy plus
nerve-sparing retroperitoneal lymph node dissection (RPLND).
Adjuvant chemotherapy is given to patients with poor histo-
logical indicators (e.g. vascular invasion and anaplastic changes).
The survival rate is 98% and the relapse rate is 5%.
. Stage II seminoma is treated by radiotherapy or chemotherapy
(with carboplatin or etoposide/platinum).
. Stage II non-seminoma is treated by orchidectomy, RPLND
and chemotherapy (with bleomycin/etoposide/platinum).
. Stage III/IV seminoma and non-seminoma are treated primarily
with multiple courses of chemotherapy (bleomycin/etoposide/
cisplatin). Surgical excision of metastases is performed in any
patient with residual disease after tumour markers have been
negative for more than 6 weeks. The primary cure rate is 85%.
. Brain metastases of testicular germ-cell tumours are treated
with a combination of chemotherapy and cranial irradiation.
45 Squamous-cell
carcinoma of the
penis
Epidemiology
. This accounts for less than 1% of all male cancers in the
developed world.
. It is rare in males who have been circumcised at birth or during
childhood.
Aetiology
. Circumcision prevents squamous-cell carcinoma (SCC) of the
penis.
. Pre-malignant lesions include Paget’s disease, De Queryrat’s
erythroplasia and Bowen’s disease of the glans penis.
Pathology
. Stage I: tumour is confined to the glans or prepuce.
. Stage II: tumour involves the penile shaft.
. Stage III: there is regional node involvement.
. Stage IV: the nodes are fixed.
134
Squamous-cell carcinoma of the penis 135
Clinical features
. An ulcer or reddened area on the glans.
. Purulent discharge.
. Inguinal lymphadenopathy.
Investigations
. Surgical biopsy.
. FNAC of enlarged inguinal nodes.
. Pelvic CT for staging.
Treatment
. Stage I is treated with radiotherapy (external beam or inter-
stitial). If this fails, partial penile amputation is performed.
Superficial lesions can be ablated by laser therapy.
. Stage II is treated with partial or total penile amputation.
Perineal urethrostomy may be performed.
. Stage III is treated with radical phallectomy and regional
lymphadenopathy (one testis should be preserved).
. Stage IV may be palliated with toilet surgery.
. The sentinel-node biopsy can be performed in order to stage the
disease.
Prognosis
. The 5-year survival rate is 80% for well-differentiated tumours
and 20% for poorly differentiated ones.
46 Primary
intracranial
tumours
Epidemiology
. The incidence is 4 per 100 000 of the general population per
year.
. They are the second commonest malignancy in children (after
leukaemia).
. There are two peaks of incidence (in the first decade and in the
fifth/sixth decades).
Aetiology
. Genetic factors. CNS tumours are a major component of some
inherited conditions such as tuberous sclerosis, neurofibro-
matosis and von Hippel–Lindau syndrome.
. Radiation.
. Immunosuppression.
Pathology
. CNS tumours can be classified according to cell origin as
glioma (the commonest type), medulloblastoma, neuroblastoma,
meningioma, schwannoma, neurofibroma and lymphoma.
. Gliomas include astrocytoma, oligodendroglioma, ependy-
moma and glioblastoma multiforme.
136
Primary intracranial tumours 137
Clinical features
. Symptoms and signs due to the local effects of the tumour on
the surrounding structures, which are destroyed or impaired
due to infiltration, mechanical pressure and/or oedema.
. Symptoms and signs of raised intracranial pressure (e.g. head-
aches, vomiting and papilloedema).
. Shifting of the intracranial contents can cause compression of
the brainstem and false localising signs.
. Seizures (complex, partial or simple).
. Progressive deterioration is the hallmark of clinical presen-
tation.
Investigations
. MRI or CT scan.
. Skull X-rays are useful in pituitary and parasellar regions.
. Technetium brain scan may confirm the site of the lesion.
. Stereotactic or CT-guided biopsy.
. Other tests include an EEG, angiography and ventriculography.

. Low-grade astrocytomas are treated by surgical excision fol-
lowed by radiotherapy (external beam, interstitial or stereotactic)
and chemotherapy (with carmustine, lomustine, procarbazine,
cisplatin and vincristine).
. Ependymoma is treated with radiotherapy to the primary
tumour site (50 Gy over a period of 4–5 weeks). Craniospinal
radiation is indicated for high-grade tumours. The overall
5-year survival rate is 40%.
. Oligodendroglioma is treated with surgical excision and post-
operative radiotherapy. Chemotherapy is indicated for recur-
rent disease. The 10-year survival rate is 35%.
. Deep-seated gliomas are treated with radiotherapy (50 Gy over
a period of 4–5 weeks).
. Medulloblastoma is treated with surgical excision (if possible)

and radiotherapy. The latter consists of brain irradiation down
to the level of C2 (30 Gy over a period of 3 weeks), a boosting
dose to the posterior cranial fossa and mid-brain and spinal
irradiation. Chemotherapy is indicated in young children and
in patients with recurrent disease.
. Meningioma is treated by complete surgical excision. If this is
not possible due to its location, radiotherapy (55 Gy over a
period of 5–6 weeks) is used. This tumour is curable.
. Pituitary tumours are treated by trans-sphenoidal excision
(if there is no suprasellar extension) or excision through a
craniotomy (if the tumour extends outside the pituitary fossa).
Post-operative radiotherapy can be given. Prolactinomas may
be treated with bromocriptine.
. Acoustic neuroma is treated by surgical excision.
. Seizures are treated with anticonvulsants (e.g. phenytoin).
. Cerebral oedema may be treated with corticosteroids (e.g.
dexamethasone) and osmotic diuretics (e.g. mannitol or urea).
. Hydrocephalus can be treated with surgical decompression
using ventriculo-peritoneal or ventriculo-atrial shunts.
47 Cerebral
metastases
Epidemiology
. Around 30% of patients with systemic cancer have cerebral
metastases.
. The metastases are solitary in 50% of cases and multiple in the
remaining 50% of cases.
Pathology
. The common primaries include breast, bronchus, melanoma,
lymphoma and prostate.
. Spread is usually haematogenous.
. The metastasis is usually surrounded by cerebral oedema.
. Haemorrhage may occur within metastases (e.g. in melanoma).
Clinical features
. Epilepsy, focal neurological deficit, raised intracranial pressure
(ICP) and cerebellar symptoms and signs.
Investigations
. MRI is the investigation of choice.
. Contrast-enhanced CT.
. Needle biopsy (under stereotactic guidance).
. Investigations of the primary lesion.
139
Treatment
. Surgical excision is indicated for surgically accessible solitary
metastases in the absence of apparent systemic disease in fit
patients. Dexamethasone (4 mg four times a day for 2 days) and
post-operative radiotherapy are given. The median survival is
2 years.
. Whole-brain radiotherapy (35 Gy) and/or steroids are indicated
for multiple metastases or surgically inaccessible lesions.
Prognosis
. The overall median survival is 6 months.
48 Spinal
metastases
Epidemiology
. Spinal metastases are found in 30% of patients dying of cancer.
. The thoracic spine is the commonest site.
Pathology
. The common primaries include breast, bronchus, kidney, thy-
roid, prostate and haematological malignancies.
. Modes of spread include haematogenous spread (the com-
monest), direct extension, perineural and lymphatic spread.
. Metastases may cause bony destruction, cord compression and
deformity, spinal oedema, ischaemia and/or infarction.
. The metastases may be extradural (the commonest type),
intradural/extramedullary or intradural/intramedullary.
Clinical features
. Pain (spinal or radicular).
. Urinary retention.
. Spastic paraplegia.
. Brown–Sequard’s syndrome.
. Neurological symptoms and signs depending upon the degree
of spinal involvement.
141
Investigations
. FBC, erythrocyte sedimentation rate (ESR), LFTs, serum
electrophoresis and serum biochemistry.
. CXR and plain radiographs of the spine.
. MRI is the investigation of choice.
. Myelography.
. CT (with or without myelography).
. CT-guided biopsy if the primary is unknown.
. Investigations for the primary lesion.
Treatment
. High-dose steroids to reduce the symptoms of cord compres-
sion and oedema.
. Radiotherapy is effective in relieving cord compression and
pain.
. Anterior spinal decompression or laminectomy is considered if
there is neurological deterioration despite the radiotherapy,
and in relatively fit patients with a good prognosis. Complete
paraplegia lasting more than 24 hours is a contraindication.
. The vertebral body can be reconstructed following anterior
decompression using methyl methacrylate and Steinmann’s
pins or iliac bone grafts.
. Posterior stabilisation of the spine may be performed following
decompression.
. Anterior decompression can be performed through a thora-
cotomy, thoraco-abdominal retroperitoneal or transperitoneal
approach, depending upon the site of compression.
Primary spinal cord tumours

. Primary tumours of the spinal cord are uncommon.
. Ependymoma is the commonest tumour. Meningiomas and
schwannomas are relatively common, whereas astrocytomas
are rare.
Spinal metastases 143
. Treatment consists of high-dose dexamethasone, surgical ex-

cision of the tumour (if possible) and post-operative radio-
therapy. Spinal cord decompression should be performed
(when indicated) even if the tumour is thought to be
unresectable.
49 Acute
leukaemia
Epidemiology
. The incidence of acute myeloid leukaemia (AML) rises with age
(to 15 per 100 000 during the eighth decade).
. Acute lymphoblastic leukaemia (ALL) accounts for 80% of
leukaemias during childhood (3 per 100 000 during the first
decade).
. AML accounts for 85% of leukaemias after the second decade.
Aetiology
. Ionising radiation.
. Benzene exposure.
. Cytotoxic chemotherapy.
. Occupational exposure (e.g. welding, DDT industries).
. Smoking increases the risk by 50%.
. Inherited syndromes (e.g. Down’s syndrome, Bloom’s syn-
drome, Fanconi’s anaemia, ataxia telangiectasia).
. Specific chromosomal abnormalities (e.g. t(8;21), t(15;17),
t(9;11), t(4;11), etc.).
. Oncogene expression (e.g. N-ras and WT1 in AML).
. Viruses.
144
Acute leukaemia 145
Pathology and classification

Morphological classification of acute
leukaemia
. ALL:
– L1: small monomorphic cells (scanty cytoplasm and fewer
nucleoli)
– L2: large heterogeneous cells (more common in adults)
– L3: Burkitt type.
. AML:
– M1: myeloblastic (no maturation)
– M2: myeloblastic (some maturation)
– M3: promyelocytic
– M4: myelomonocytic
– M5: monocytic
– M6: erythroleukaemia
– M7: megakaryoblastic.
. Cytochemical staining helps to determine the type of leukaemia
in doubtful cases.
. Immunological classification of leukaemia assists understand-
ing of the pathogenesis of the disease.
Clinical features
. ALL.
– The symptoms include malaise, fever, bone pains, oral and
pharyngeal ulceration and petechiae.
– The signs include pallor, lymphadenopathy, hepatosplen-
omegaly, haemorrhages and bone tenderness. Mediastinal
masses are more common in adults.
– Symptoms and signs of malignant meningitis are occasion-
ally present.
. AML.
– The clinical features are similar to those of ALL.
– Bone pain, lymphadenopathy and CNS involvement are less

common than in ALL.
– Gum hypertrophy is relatively common in M4 and M5.
Investigations
. FBC may reveal anaemia, thrombocytopenia and leukocytosis.
Lymphoblasts or myeloblasts are usually present. The white
blood count (WBC) may not be elevated.
. Bone-marrow examination must show more than 30% blast
cells.
. Cytochemical staining and immunological typing are used
when appropriate.
. Serum biochemistry.
. Clotting screen.
. CXR may show a mediastinal mass, especially in T-cell leu-
kaemia, due to thymic enlargement.
. Plain radiographs may show osteolytic lesions, demineral-
isation and/or radiolucent bands in the metaphysis.
. Lumbar puncture should be performed if indicated.
Treatment
. ALL.
– Remission induction is achieved by means of vincristine,
prednisolone and doxorubicin, followed by an intensive con-
solidation regimen consisting of doxorubicin, asparaginase,
methotrexate and cytosine arabinoside.
– CNS prophylaxis consists of cranial radiation (18 Gy in
10 fractions over 2 weeks) plus intrathecal methotrexate.
CNS disease is treated by craniospinal radiation (24 Gy over
2 weeks).
– Testicular disease is treated by radiotherapy (24 Gy over
2 weeks).
– Maintenance therapy is continued for 2 years. Methotrexate,
vincristine, prednisolone and mercaptopurine are used.
Acute leukaemia 147
– Relapse within the first year of treatment is an indication

for bone-marrow transplantation (BMT). Further intensive
chemotherapy is indicated to re-induce remission in cases
that relapse after 1 year of treatment.
– BMT is also indicated in cases with a poor prognosis and in
the second and third remission.
– Allogenic BMT has a 5-year relapse-free survival rate of
65% in the second remission and a 3-year survival rate of
55% in the first remission. Leukaemia cells are destroyed by
chemotherapy (e.g. cyclophosphamide) plus total body ir-
radiation. Immunosuppressive therapy such as cyclosporin
and methotrexate is used to prevent graft versus host disease
after allogenic BMT.
– Autologous BMT is also possible, but with less impressive
results.
– Treatment of adult ALL is similar to that of childhood ALL.
However, the induction and maintenance treatments are
more intense in view of the poorer prognosis.
– Supportive care includes blood and platelet transfusions,
antimicrobials and allopurinol.
. AML.
– Induction of remission is achieved with cytosine arabinoside,
doxorubicin and 6-thioguanine. The mortality risk during
induction is 10%.
– Maintenance therapy includes cytosine arabinoside, cyclo-
phosphamide, methotrexate, etoposide, 5-azacytidine and
6-mercaptopurine.
– Arsenic trioxide seems to be promising in the treatment of
acute promyelocytic leukaemia (PML). The mechanism of
action seems to involve the PML–retinoic acid receptor–
alpha (PML-RAR-alpha) fusion protein.
– All-trans-retinoic acid (ATRA) is used in patients with M5 to
prevent disseminated intravascular coagulopathy (DIC).
– Supportive care includes blood and platelet transfusions, IV
fluids, IV antimicrobials, haematopoietic growth factors,
aseptic techniques when dealing with central venous cath-
eters (e.g. Hickman line) and allopurinol.
– Relapse is treated by re-induction chemotherapy or BMT.
Prognosis
. ALL.
– The overall 5-year survival rate is 80% in girls and 50% in
boys. The prognosis is worse in adults.
. AML.
– The overall 10-year disease-free survival rate is 25%. The
prognosis is worse in patients over 30 years of age and with a
high WBC.
50 Chronic
leukaemia
Epidemiology
. Chronic lymphocytic leukaemia (CLL) is a disease of the elderly.
. Chronic myelocytic leukaemia (CML) occurs in all age groups.
Aetiology
. See aetiology of acute leukaemia on page 144.
. Philadelphia chromosome (reciprocal translocation of part of
the long arm of chromosome 22 to chromosome 9) occurs in
most cases of CML. In this myeloproliferative disorder the
t(9;22) reciprocal translocation results in the generation of a
novel fusion oncoprotein, BCR-ABL, with constitutive tyro-
sine kinase activity.
. Trisomy of chromosome 12 and deletion 13q14 occur in CLL.
. There is p53- and RB1-altered expression.
Pathology
. Around 95% of CLL cases are of the B-cell type. The T-cell type
(5% of cases) causes less immunoglobulin suppression and less
lymphadenopathy. Autoimmune haemolytic anaemia occurs
in 10% of CLL patients.
. Hypercellular bone marrow with lymphocytic or myeloid re-
placement.
. Infiltration of liver, spleen and lymph nodes.
149
. CLL can be subdivided into four stages depending upon the

presence of anaemia, lymphadenopathy, splenomegaly and
thrombocytopenia.
Clinical features
. The patient may be asymptomatic.
. Symptoms include malaise, fatigue, weight loss, bruising and
bleeding, abdominal discomfort, bone pains and fever.
. Signs include pallor, purpura, lymphadenopathy (especially in
CLL), splenomegaly, hepatomegaly and signs of infection.
Investigations
. Blood count and film. In CLL the lymphocyte count exceeds
10 109/l (small well-differentiated lymphocytes). In CML
there is leukocytosis with an increase in all granulocyte series,
especially myelocytes. Anaemia and thrombocytopenia are
common.
. Bone-marrow examination.
. Lymph-node biopsy.
. Leukocyte alkaline phosphatase.
Treatment
. No treatment is indicated in asymptomatic patients. Blood
counts are monitored regularly.
. Symptomatic patients with CLL are treated with chlorambucil
(3 mg daily) until remission occurs. Relapse is treated with
further chemotherapy. Other effective drugs include fludarabine
and prednisolone. The latter is particularly useful in patients
with bone-marrow failure.
. Symptomatic patients with CML are treated with busulfan
(70 mg/kg) until remission occurs (WBC < 20 109/l). Relapse is
treated with further chemotherapy. Other effective drugs include
hydroxyurea and interferon-a.
Chronic leukaemia 151
. Imatinib mesylate represents the first of a new generation of

molecular-targeted therapies for chronic myeloid leukaemia.
This agent inhibits the tyrosine kinase activity of BCR-ABL.
. Blastic transformation of CML is treated appropriately as for
AML and ALL.
. Allogenic BMT is considered during the first remission in
patients with CML who are under 50 years of age and have a
matched donor.
. Supportive care includes treatment of infections and trans-
fusion of blood products (platelets and red blood cells).
Prognosis
. CLL.
– The overall median survival is 5 years.
– Poor prognostic indicators include lymphadenopathy, splen-
omegaly, anaemia and thrombocytopenia.
. CML.
– The 5-year survival rate is less than 5%.
– Allogenic BMT in suitable patients appears to cure 40% of
patients, but long-term results are still awaited.
– The Philadelphia-negative type has a poorer prognosis.
Hairy cell leukaemia

. This is regarded as a B-cell leukaemia.
. It is more common in males, especially during the sixth and
seventh decades of life.
. It is usually readily diagnosed by observation of typical hairy
cells (HCs) in the blood film. The diagnosis is then confirmed
by tartrate-resistant acid phosphatase staining, marker anal-
ysis and bone-marrow examination.
. Anaemia, thrombocytopenia, neutropenia and splenomegaly
are common features.
. Chlorodeoxyadenosine is the treatment of first choice. Deoxy-
coformycin and rituximab (anti-CD20) are useful for the treat-
ment of relapsed/refractory disease.
51 Hodgkin’s
lymphoma
Epidemiology
. The incidence is approximately 1.8 per 100 000 per year in
Western countries. However, there is geographical variation.
. The incidence shows a bimodal age distribution with the first
peak occurring between the ages of 15 and 30 years and the
second peak occurring above the age of 50 years.
. The male:female ratio is 1.5:1.
Aetiology
. Familial tendency.
. The human leukocyte antigens (HLAs) HLA-A1 and HLA-A12
are both associated with the disease.
. Epstein–Barr virus genome can be detected in 40% of all cases.
Pathology
. Reed–Sternberg or mononuclear Hodgkin’s cells are charac-
teristic.
. Histological types:
– lymphocyte-depleted
– lymphocyte-predominant
– mixed cellularity
– nodular sclerosis.
152
Hodgkin’s lymphoma 153
. The lymphocyte-predominant type has the best prognosis,

whereas the lymphocyte-depleted type carries a poor prog-
nosis.
Clinical features
. Lymphadenopathy. The neck is the most frequent site at pres-
entation (70% of cases), followed by the axilla (20%) and
groin (10%).
. Constitutional symptoms (fever, weight loss, pruritus and
sweats) occur in 25% of patients. Alcohol-induced pain is
reported in 3% of cases.
. Other features include autoimmune haemolytic anaemia, im-
mune thrombocytopenia, erythema multiforme, erythroderma,
lymphoderma, superior/inferior vena cava obstruction, ob-
structive jaundice, ureteric obstruction and paraneoplastic
syndromes.
. Hodgkin’s disease may involve the spinal cord, lung, bone
marrow, skin, gut, liver and/or spleen.
Investigations
. FBC, ESR and serum biochemistry.
. CXR (mediastinal and bronchopulmonary lymphadenopathy,
thymus enlargement).
. Thoracic and abdominal CT.
. Positron emission tomographic (PET) scanning. As it assesses
differences in the metabolic activity of cancer cells, PET scan-
ning may be superior to computerised tomographic scanning,
which is limited to showing structural anatomical abnormali-
ties.
. Biopsy (excisional or percutaneous).
. Other investigations include lymphangiography, bone-marrow
trephine and bone scan.
. Barium studies (if indicated).
Ann Arbor staging system

. Stage I: involvement of a single node region or a single extra-
lymphatic site or organ.
. Stage II: involvement of two or more node regions on the same
side of the diaphragm. Involvement of a single extranodal site
plus one (or more) node regions on the same side of the
diaphragm.
. Stage III: involvement of lymph nodes on both sides of the
diaphragm which may include the spleen or an extranodal site.
. Stage IV: diffuse involvement of one or more extra-lymphatic
organs.
. A: no constitutional symptoms.
. B: constitutional symptoms present.
Treatment
. Standard treatment consists of combined-modality therapy
that includes an abbreviated course of chemotherapy and
involved-field radiation. As this continues to include radiation
therapy, patients will remain at risk of long-term toxicities that
include the development of second cancers and cardiovascular
events. Recent studies testing the role of chemotherapy alone
are now available. They demonstrate that the omission of
radiation therapy results in a small but statistically significant
reduction in disease control, but no detectable differences in
overall survival. Further follow-up will clarify whether chemo-
therapy alone is the preferred treatment option. At present
patients should be informed of the trade-offs involved in choosing
between this option and combined-modality therapy.
. Stages IA and IIA: an abbreviated course of chemotherapy
followed by radiotherapy to the involved and adjacent lymph
nodes (40 Gy in 20 fractions).
. Stage IIIA: combination chemotherapy, such as MOPP (mustine,
oncovin, procarbazine and prednisolone) or ABVD (adriamycin,
bleomycin, vinblastine and dacarbazine). Radiotherapy is used
for residual and recurrent disease.
Hodgkin’s lymphoma 155
. Stages IIB, IIIB and IVB: combination chemotherapy.

. High-dose chemotherapy with stem-cell support is indicated
for extensive disease that fails to respond to standard chemo-
therapy regimens.
Prognosis
. The 10-year survival rates are as follows:
– 80% for stage IA
– 77% for stage IIA
– 72% for stage IIIA
– 65% for stage IIB
– 55% for stage IV.
52 Non-Hodgkin’s
lymphoma (NHL)
Epidemiology
. The incidence increases with age.
. There is a slight male predominance.
. There is geographical variation in incidence and site. Burkitt’s
lymphoma (of the jaw) is common in Africa. Middle Eastern
lymphoma usually affects the intestine.
Aetiology
. Viruses – human T-cell leukaemia viruses HTLV1 and HTLV2,
Epstein–Barr virus (EBV) and the herpes simplex virus HSV-6
have all been implicated.
. Immunosuppression, including congenital syndromes, and
AIDS predispose to NHL.
. Coeliac disease predisposes to T-cell lymphoma of the intes-
tine.
. Genetic factors – chromosomal translocation between chro-
mosomes 8 and 14 and C-myc over-expression – may contribute
to aetiology.
Pathology
. B-cell lymphoma (follicular, diffuse, Waldenström’s, chronic
lymphocytic leukaemia (CLL), Burkitt’s lymphoma and heavy-
chain disease) accounts for 90% of cases.
156
Non-Hodgkin’s lymphoma (NHL) 157
. T-cell lymphoma (cutaneous thymic and peripheral-cell lym-

phoma) accounts for 10% of cases.
. NHL can be classified as low grade, intermediate grade or high
grade.
. Immunological classification is helpful.
Clinical features
. Lymphadenopathy. The neck is the commonest site.
. Hepatosplenomegaly.
. Compression of structures (e.g. veins, ureters, hepatobiliary
ducts, etc.) and constitutional symptoms (fever, sweats and
weight loss).
Staging
. This is the same as for Hodgkin’s disease.
. Most patients have stage III or stage IV at presentation.
Investigations
. FBC and film, ESR, serum biochemistry.
. CXR. Thoracic and abdominal CT.
. Biopsy (excisional or percutaneous).
. Other investigations include bone scan, lymphangiography
and bone-marrow trephine.
. Barium studies and IVU may be indicated.
Treatment
. Follicular lymphoma (40% of cases).
– Stage I and II (small-cell and mixed) disease is treated by
radiotherapy to the involved and adjacent lymph nodes.
– Stage I and II (large-cell) disease is treated by radiotherapy

and chemotherapy (CHOP regimen: cyclophosphamide, dox-
orubicin, vincristine and prednisolone).
– Stage III and IV disease is treated with chemotherapy (low-
dose or high-dose) and interferon-a.
. Intermediate- and high-grade lymphoma (diffuse) is treated
with combination chemotherapy (high-dose).
. High-dose chemotherapy with peripheral stem-cell support or
autologous bone-marrow transplantation is indicated for NHL
that is unresponsive to standard regimens, and for recurrent
disease.
. Large-cell NHL in childhood is treated with an intensive
induction course of chemotherapy followed by a consolidation
phase and a maintenance course of alternating pairs of drugs.
. Recent research suggests that rituximab is safe and effective in
the treatment of refractory or relapsed low-grade or follicular
CD20 B-cell non-Hodgkin’s lymphoma.
Prognosis
. Follicular lymphoma has a 10-year survival rate of:
– 78% for stage I
– 60% for stage II
– 52% for stage III
– 38% for stage IV.
. Diffuse intermediate and high-grade NHL has a 3-year disease-
free survival rate of 50%.
. Large NHL in childhood has a 5-year survival rate of 70% with
modern management.
. Recurrent disease has a 3-year survival rate of 35% with high-
dose chemotherapy.
53 Multiple
myeloma
Epidemiology
. The incidence is approximately 3 per 100 000 per year. It
increases with age.
. Men are more commonly affected than women.
Pathology
. Infiltration of bone and bone marrow by malignant plasma
cells causing osteoporosis, osteopenia, lytic lesions and patho-
logical fractures.
. Paraproteinaemia (IgG, IgA, Bence–Jones, IgM and/or IgD)
occurs in 99% of cases.
. Renal impairment (light-chain deposition in the distal tubule,
hyperuricaemia, amyloidosis and hypercalcaemia).
Clinical features
. Diffuse bone pain is the commonest symptom (67% of cases).
Pathological fractures and cord compression may occur.
. Anaemia, recurrent infections, fatigue, nausea and hypercal-
caemia.
. Hyperviscosity syndrome.
. Hepatomegaly, splenomegaly and lymphadenopathy are un-
common.
159
. Other clinical features include congestive cardiac failure and

renal impairment.
Investigations
. FBC, ESR, serum biochemistry and viscosity.
. Serum immunoglobulins and immunoelectrophoresis.
. b2-microglobulin–plasma/urine.
. Bone-marrow aspiration and trephine.
. 24-hour urinary light chains, proteins and calcium.
. Radiological skeletal survey.
Treatment
. Serious complications (e.g. dehydration, hypercalcaemia and
spinal cord compression) should be treated promptly with
appropriate measures (e.g. fluid replacement, bisphosphonates
and radiotherapy to the spinal cord).
. Combined melphalan–prednisolone oral therapy is the first
line of treatment (6 to 9 courses). H2-antagonists are usually
added to therapy and interferon-a may be used as a maintenance
therapy. The response rate is 60%. Some centres use more
complex regimens of combination chemotherapy.
. Second-line chemotherapy includes agents such as doxorubicin,
vincristine and nitrosoureas. Hemi-body irradiation is also
effective as a second-line therapy.
. High-dose chemotherapy and bone-marrow transplantation
(autologous or allogenic) may improve outcome in selected
patients.
. Radiotherapy for painful bony deposits, spinal cord com-
pression and bones at risk of fracture.
. Internal fixation for pathological fractures and bones at risk.
. Supportive measures (e.g. blood transfusions and antibiotics).
. Monoclonal immunoglobulin levels can be used to monitor
response to treatment.
. Recent research suggests that thalidomide has a role to play in
the management of multiple myeloma.
Multiple myeloma 161
Prognosis
. This depends upon tumour mass.
– The median survival is 5 years for low tumour mass, 2 years
for intermediate tumour mass and 6 months for high tumour
mass.
– High serum urea levels (> 10 mmol/l) and low Hb levels
(< 7.5 g/dl) are predictors of poor outcome.
Waldenström’s macroglobulinaemia
. There is production of monoclonal IgM and infiltration of
bone marrow by lymphoid cells.
. Clinical features include hyperviscosity, weakness, haemolytic
anaemia, purpura, bleeding disorders, hepatosplenomegaly and
lymphadenopathy.
. The disease is slowly progressive, and symptomatic cases require
treatment in the form of oral chlorambucil or cyclophosphamide
(small dose). Plasmapheresis is effective in reducing hyper-
viscosity.
. Multiple myeloma chemotherapy protocols can be used to
treat aggressive disease.
. The median survival is 4 years.
54 Miscellaneous
Carcinoma of the maxillary antrum

. This is usually diagnosed late after it has invaded surrounding
structures.
. Unilateral nasal obstruction and bloodstained nasal discharge
are early symptoms. The late clinical features include swelling
of the cheek, swelling/ulceration of the palate or the bucco-
alveolar sulcus, epiphora, proptosis, diplopia, pain and regional
lymphadenopathy (submandibular and cervical).
. Systemic metastases are rare.
. Investigations include plain X-rays, CT and biopsy.
. The tumour is treated by wide local excision (maxillectomy)
combined with orbital extenteration if the orbit is involved,
followed by radiotherapy.
. Unresectable tumours are treated by radiotherapy and chemo-
therapy.
. Management also includes reconstruction of surgical defects
using temporalis muscle slings, skin grafts or composite bone
flaps.
Cancer of the nasopharynx

. This type of cancer is relatively common in south China.
. Squamous-cell carcinoma accounts for most cases. Lymphoma
and adenoid cystic carcinoma are rare.
. The clinical features include nasal obstruction, bloodstained
nasal discharge, cranial nerve palsies and cervical lympha-
denopathy.
162
Miscellaneous 163
. Radiotherapy is the mainstay of treatment after three-

dimensional radiation planning (up to 15 fields in a single
patient). The neck is included in the radiation fields.
. Surgery is reserved for residual or recurrent disease.
. Chemotherapy is used for advanced disease in selected
patients.
. The local control rate for T1 and T2 tumours is 90%,
compared with 45–75% for T3 and T4 tumours.
Mesothelioma
. This is a malignant tumour of the pleura or pericardium.
. Pleural mesothelioma is strongly associated with exposure to
blue (crocidolite) and brown (amosite) asbestos. The latent
interval between exposure and development of disease is
approximately 30 years.
. The tumour tends to spread over the pleural surface encasing
the lung and to invade the mediastinum, diaphragm and chest
wall. A bloodstained pleural effusion is a common finding.
. Patients (aged approximately 60 years) usually present with
dyspnoea, cough and chest pain.
. Investigations include CXR, CT, cytological analysis of pleural
effusions, thoracoscopy and biopsy.
. Treatment is unsatisfactory. It includes surgical resection for
localised lesions, radiotherapy and/or chemotherapy (systemic
and/or intrapleural). Cisplatin and interferon-a have a 20%
response rate.
. The prognosis is poor, with a median survival of 18 months
from diagnosis.
Chondrosarcoma
. This is the second commonest malignant tumour of bone. The
pelvis is most commonly involved.
. The disease may arise in benign enchondroma.
. Plain X-rays may show bone destruction and flecks of calcifi-

cation. CT can demonstrate the extent of the lesion.
. Surgical excision of the lesion with endoprosthesis (if required)
is the mainstay of management.
. Radiotherapy is used for palliation. Chemotherapy is occasion-
ally used.
Ewing’s sarcoma
. This is a malignant round-cell tumour of bone with a peak
incidence during the second decade of life.
. The pelvis and femur are most commonly affected.
. Clinical features include swelling, pain, fever, weight loss and
dyspnoea due to pulmonary metastases.
. Investigations include plain X-rays, CT, MRI and biopsy.
. Treatment consists of radical radiotherapy combined with
adjuvant chemotherapy (doxorubicin, cyclophosphamide, vin-
cristine, actinomycin D and ifosfamide).
. The 5-year survival rate for patients with localised disease is
55%.
Cutaneous T-cell lymphoma (‘mycosis

fungoides’)
. The peak incidence occurs during the fifth and sixth decades of
life.
. It is equally common in men and women.
. The disease has four stages:
– stage I – plaque or eczematous skin lesions
– stage II – plaque with enlarged lymph nodes that are patho-
logically negative
– stage III – erythroderma
– stage IV – visceral enlargement of pathologically positive
nodes.
. Sézary’s syndrome is a form of disseminated disease.
Miscellaneous 165
. Treatment modalities include PUVA, wide-field radiation,

whole-body electron therapy and/or chemotherapy (alkylating
agents and interferon).
Merkel-cell tumour
. This is a rare primary cutaneous neuroendocrine tumour.
. It usually presents as a discrete nodular mass.
. The tumour is primarily treated by surgery and post-operative
radiotherapy.
. Chemoradiation is indicated for advanced and recurrent cases.
Uveal melanoma
. The incidence is 0.6 per 100 000 per year. It is the commonest
intra-ocular malignancy in adults.
. Around 85% of lesions arise in the choroidal part, and the
remainder arise in the ciliary body and iris.
. Clinical features include a visual field defect, pain, secondary
glaucoma and retinal detachment. Systemic metastases are
common.
. Treatment modalities include photocoagulation, cryotherapy,
radiotherapy and/or surgery.
. Indications for enucleation include pain, secondary glaucoma,
invasion of surrounding structures and macular/optic nerve
involvement.
Squamous-cell carcinoma of the

bladder
. This accounts for 3% of all bladder cancers.
– chronic infection (e.g. Schistosoma haematobium cystitis)
– stones
– long-term catheterisation and neuropathic bladders.
. The disease is usually advanced at presentation.

. The tumour is treated by radical cystectomy.
. The tumour is not radiosensitive.
Neuroblastoma
. This arises from adrenal or neural-crest tissue.
. It occurs in 1 in 10 000 live births.
. Clinical features include abdominal mass, neurological signs
and symptoms, Horner’s syndrome and distant metastases
(liver, skin and bone).
. Investigations include bone-marrow aspiration, urinary analy-
sis, VMA, CXR, FBC, serum biochemistry, bone scan, USS, CT
and/or MRI.
. Treatment consists of surgical debulking and adjuvant radio-
therapy. Other treatment modalities include chemotherapy
and autologous bone-marrow transplantation.
. The prognosis depends upon stage, age, location, site of
metastases, presentation and the presence of the N-myc
oncogene.
. The overall survival rate ranges from 10% to 90% depending
upon the stage of the disease.
55 Long-term
venous access
Indications
. Administration of cytotoxic drugs.
. Total parenteral nutrition (TPN).
. Transfusion of blood products.
. Administration of antimicrobials.
. Bone-marrow or peripheral stem-cell infusion.
Catheters
. These are usually made of silicone (which has low thrombo-
genicity and is flexible) or polyurethane.
. They can be single, double or triple lumen. The latter type is
associated with a higher incidence of sepsis.
. Hickman lines are wide-bore silicone catheters which were first
described in 1979. Groshing lines are similar to Hickman lines
but have self-sealing valves to prevent reflux of blood into the
line.
Insertion techniques
. Catheters can be inserted using a surgical cut-down technique
or a percutaneous (Seldinger) introducer kit.
. Ultrasound imaging can be used to guide the procedure.
. The procedure can be performed under general or local anaes-
thesia.
167
. The internal jugular, subclavian, external jugular and cephalic

veins are usually selected for cannulation. The inferior vena
cava is occasionally selected (e.g. in cases of superior vena cava
(SVC) obstruction).
. The operating table is tilted head-down to allow distension of
veins and prevent air embolism.
. The catheter tip should lie at the right atrium/SVC junction or
in the SVC. X-ray control is used to confirm the catheter
position.
. The catheter should be tunnelled subcutaneously so that the
exit point is approximately 15 cm down the chest wall. Tun-
nelling aids line stabilisation and reduces the infection risk.
. A Dacron cuff is positioned near the skin exit site, and the
induced fibrosis aids stabilisation of the line.
. Totally implantable devices have ports or reservoirs with a self-
sealing silicone septum (e.g. Port-Cath).
. Totally implantable pumps are also available.
Complications
. Sepsis.
– Skin exit site infection requires dressing and antimicrobials
(e.g. vancomycin).
– Tunnel infection requires catheter removal.
– Catheter tip infection responds to vancomycin if it is due to
Staphylococcus epidermidis. Removal is frequently required.
. The incidence of pneumothorax should be less than 3%.
. Air embolism.
. Injury of neighbouring structures during catheter insertion.
. Catheter fracture.
. Catheter occlusion can be treated with heparin or strepto-
kinase (250 000 units). Low-dose warfarin can be used to
prevent obstruction due to clot formation.
. Vein thrombosis.
. Extravasation of drugs can occur with totally implantable
devices.
Long-term venous access 169
Principles of catheter care

. Aseptic technique.
. Flushing with heparin/saline once weekly if the catheter is not
in regular use. Totally implantable devices may be flushed once
monthly.
. Nurses’ training.
. Patients’ education.
56 Pain control in
advanced cancer
. Pain is a complex symptom with sensory and emotional

components. Its severity should be decided by the patient and
not by the carer.
. Empathy, good communication skills and regular assessment
are essential to pain management.
. The cause of pain should be accurately diagnosed and removed
if possible.
. The analgesic is chosen in a stepped approach (the analgesic
ladder) as follows.
– Step 1: non-opioids (e.g. paracetamol 1 g 6-hourly, ibuprofen
200–600 mg 8-hourly, diclofenac 50 mg 8-hourly, Entonox,
nefopam, etc.).
– Step 2: weak opioids (e.g. codeine and dihydrocodeine).
– Step 3: strong opioids (e.g. morphine, diamorphine for sub-
cutaneous route and fentanyl for transdermal administration).
. The starting dose of strong opioids depends upon the previous
analgesic needs and on renal function. Hepatic dysfunction has
a limited clinical impact on opiate metabolism.
. Secondary analgesia relieves pain through an indirect mechan-
ism. Secondary analgesics include antidepressants (e.g. ami-
triptyline, lofepramine), corticosteroids, antispasmodics (e.g.
hyoscine butylbromide), carbamazepine, sodium valproate
and membrane-stabilising drugs.
. Spinal analgesia via an intrathecal catheter (strong opioid/
bupivacaine mixture) has a role in patients who are unable to
tolerate the adverse effects of systemic opioids.
. Peripheral nerve blocks may also be used in pain control.
. The management of bone metastases also includes radiotherapy,
orthopaedic fixation of pathological fractures, bisphosphonates
170
Pain control in advanced cancer 171
(e.g. clodronate), nerve block and hormonal manipulation

where appropriate.
. Neurosurgical procedures for pain control (e.g. cordotomy for
unilateral pain) are occasionally required, and liaison with
neurosurgical colleagues is needed.
57 Symptom
control in
advanced cancer
. Pain is a complex symptom with sensory and emotional

components. Its severity should be decided by the patient and
not by the carer (see Chapter 56).
. Nausea and vomiting.
– The choice of an anti-emetic depends upon the cause. A
single anti-emetic is sufficient in most cases.
– The cause (e.g. hypercalcaemia) should be specifically treated if
appropriate.
– Antihistamines such as cyclizine and hyoscine hydrobromide
are effective in the treatment of vomiting due to stimulation
of vomiting centres.
– Potent dopamine antagonists such as haloperidol are effec-
tive in the treatment of vomiting due to stimulation of the
chemoreceptor trigger zone.
– Peripheral dopamine antagonists such as metoclopramide
and domperidone are effective in the treatment of vomiting
due to gastric stasis.
– Other useful anti-emetics include ondansetron (serotonin
antagonist) and cisapride (gastrointestinal stimulant).
– Associated management of nausea and vomiting includes
dexamethasone, nasogastric drainage and percutaneous gas-
trostomy.
. Dysphagia.
– Malignant dysphagia can be relieved by oesophageal intu-
bation, radiotherapy, laser therapy or dexamethasone.
– Viral infections and candidiasis causing dysphagia should be
appropriately treated (e.g. with fluconazole, Zovirax, etc.).
172
Symptom control in advanced cancer 173
– Hydration and feeding can be achieved via gastrostomy.

– The swallowing therapist may play an important role.
. Bowel obstruction.
– The causes include recurrent abdominal tumour, metastatic
obstruction, a primary tumour, constipation, benign ad-
hesions and ileus.
– Surgery should be considered in fit patients with obstruction
that is suspected to be due to a single site obstruction or
benign adhesions, provided that the patient is willing to
undergo surgery.
– Hyoscine can be used to relieve colic.
– Most patients will absorb sufficient fluid from their upper GI
tract to prevent symptomatic dehydration. Parenteral nutrition
is only indicated during pre-operative preparation for surgery.
. Diarrhoea.
– Causes such as constipation, infection, partial bowel ob-
struction, carcinoid syndrome and post-gastrectomy syn-
drome should be considered.
– Management includes rehydration and loperamide.
– Management of steatorrhoea includes loperamide, ranitidine,
pancreatin supplement and/or biliary drainage (bypass sur-
gery or endoscopic stenting).
– Blind-loop syndrome can be treated with antibiotics (e.g.
tetracycline, metronidazole).
– Radiotherapy-induced diarrhoea responds to non-steroidal
anti-inflammatory drugs (NSAIDs).
– Octreotide is used to treat severe refractory diarrhoea.
. Constipation.
– This should be prevented in high-risk patients by regular use
of co-danthrusate (2 capsules at night). The laxative dose is
titrated according to the opiate dose in order to maintain
comfortable stools.
– If the rectum is full, constipation is treated with glycerine
suppositories and phosphate enemas. If this approach is unsuc-
cessful, manual evacuation under sedation should be considered.
– Other drugs used in the treatment of constipation include
bisacodyl (10–20 mg orally or by rectum) and docusate
(100–300 mg three times a day).
. Oral problems.
– Oral hygiene is essential.
– Aphthous ulceration is treated with tetracycline suspension
and topical corticosteroids.
– Fungal infections are treated with fluconazole (a single dose)
and nystatin suspension.
– Benzydamine hydrochloride (Difflam) mouthwash provides
effective oral analgesia.
. Anorexia.
– This can be helped with corticosteroids (e.g. dexamethasone
4 mg daily) or megestrol (160 mg daily).
. Ascites.
– The commonest causes of malignant ascites are carcinomas
of the bronchus, breast, stomach, pancreas, colon and ovary.
– Paracentesis offers immediate relief, and can be achieved
using a peritoneal dialysis catheter inserted through the left
iliac fossa or the mid-line suprapubically under local anaes-
thesia. The ascites is drained to dryness over a period of
6 hours and a colostomy bag is placed over the puncture site.
– Spironolactone combined with frusemide aids long-term
control.
– A peritoneo-venous shunt (LeVeen shunt) can be inserted
under a general anaesthetic in suitable patients.
. Pleural effusions.
– Pleural effusions are worth draining (1.5 l at a time) if they
are symptomatic. If the effusion recurs, pleurodesis with 1 g
of tetracycline is indicated after drainage to dryness through
an intercostal drain. Talc powder achieves 100% control
rate but causes a vigorous reaction.
– Pleuroperitoneal shunt is a recognised treatment modality in
selected patients.
. Anxiety and depression.
– Anxiety is relieved by empathy, explanation, counselling and
relaxation.
– Depression (early-morning wakening, self-blame, feelings of
worthlessness and loss of interest in life) can be effectively
treated with antidepressants (e.g. amitriptyline 75–150 mg
daily or lofepramine 140–210 mg daily).

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Concise Notes in

Kefah Mokbel MB, BS (Lon), FRCS (Eng), MS (Lon),

© 2005 by Kefah Mokbel

No claim to original U.S. Government works

International Standard Book Number-13: 978-1-138-03052-7 (eBook - PDF)

and the CRC Press Web site at

Preface to the third edition vi

Principles of cancer screening 1

21 Carcinoma of the pancreas 72

53 Multiple myeloma 159

This book has two objectives. It is intended to provide an accurate,

Professor Kefah Mokbel is Consultant Breast and Endocrine Sur-

ACTH adrenocorticotrophic hormone

FBC full blood count/familial breast cancer

TSG tumour suppressor gene

Reliability of a screening test

Biases within a screening programme

Attributes of a screening programme

. The median value of a set of data is the central observation after

Parametric tests such as the two-sample t-test and the paired

(RR) is the ratio of proportions in two groups which can be

. Phase I clinical trials focus on drug toxicity and dosing schedules.

Host factors in carcinogenesis

Environmental factors in carcinogenesis

– hepatitis B virus (HBV). The incidence of hepatocellular

Mechanisms of cancer pathogenesis

Tumour suppressor genes (TSGs)

DNA repair genes

The sequential steps of metastasis

. N indicates whether the cancer has spread to the regional

Gene expression profiling

The cell cycle

Figure 1 The cell cycle. M = mitosis phase, G1 = gap 1, S = synthesis

. The duration of the cell cycle is approximately 48 hours.

Classification of cytotoxic drugs

Mechanisms of drug resistance

. Angiogenesis inhibitors include angiotensin, endostatin and

. The effects of radiotherapy depend on the dose, the tumour

. SCC on the upper jaw is treated with surgical excision and

. Other features include strabismus, glaucoma, defect in visual

. Large-cell carcinoma (10% of cases).

. CT scanning to guide thoracic needle biopsy and to define

Staging (TNM system)

Treatment and prognosis

– The 5-year survival rate for resectable tumours is 55% for

. Papillary carcinoma is rare and has a good prognosis.

biopsy (SNB) using the dual localisation technique should be

– Post-menopausal women with ER- and/or PgR-positive LABC

Familial breast cancer (FBC)

Recent advances and future

. Digital mammography seems to achieve better-quality images

. Preliminary studies have suggested that fluoro-2-deoxy-D-

– complete eradication rate is 5%

. N1: metastasis in 1–6 regional nodes.

– There is no evidence that D2 resection improves survival in

. Southern blot DNA hybridisation of fresh biopsy specimens.

. Serum carcino-embryonic antigen (CEA).

– A colonic pouch–anal anastomosis may be performed for

– Systemic 5-FU and folinic acid may be given for inoperable

Treatment and prognosis