Dr. Thaere Jasim
Tikrit University college of medicine
oncology is becoming a larger portion of
surgical practice. The surgeon often is
responsible for the initial diagnosis and
management of solid tumors. Knowledge of
cancer epidemiology, etiology, staging, and
natural history is required for initial patient
assessment, as well as to determination of the
optimal surgical therapy.
Cancer cells are psychopaths.
They have no respect for the rights of other
cells. They violate the democratic principles
of normal cellular organisation.
Their proliferation is uncontrolled; their
ability to spread is unbounded. Their
inexorable, relentless progress destroys first
the tissue and then the host.
Tumour Cells have to acquire a number of characteristics before
they are fully malignant.
■ Establish an autonomous lineage
Resist signals that inhibit growth
Acquire independence from signals stimulating growth
■ Obtain immortality
■ Evade apoptosis
■ Acquire angiogenic competence
■ Acquire the ability to invade
■ Acquire the ability to disseminate and implant
■ Evade detection/elimination
■ Genomic instability
■ Jettison excess baggage
■ Subvert communication to and from the
Establish an autonomous lineage:
This involves developing independence from the
normal signals that control supply and demand.
Cancer cells escape from this normal system of
checks and balances: they grow and proliferate in
the absence of external stimuli; they proliferate and
grow despite signals telling them not to. Their
division is inappropriate and remorseless.
normal cells are permitted to undergo only a finite
number of divisions.
For humans, this number is between 40 and 60. The
limitation is imposed by the progressive shortening
of the end of the chromosome, the telomere,
that occurs each time a cell divides.
Telomeric shortening is like a molecular clock and,
when its time is up, it is time for that lineage to die
Apoptosis is a form of programmed cell death.
Cells that should not be where they find themselves to be
should, normally, die by apoptosis: death by apoptos is an
important self-regulatory mechanism in growth and
Genes, such as p53, that can activate apoptosis function
as tumour suppressor genes. Loss of function in a tumour
suppressor gene will contribute to malignant
Cancer cells will be able to evade apoptosis, which
means that the wrong cells can be in the wrong places at
the wrong times..
:Acquire angiogenic competence
A mass of tumour cells cannot, in the absence of a
blood supply, grow beyond a diameter of about
This places a severe restriction on the capabilities of
the tumour: it cannot grow much larger and it cannot
spread widely within the body.
However, if the mass of tumour cells is able to
attract or to construct a blood supply, then it is able
to quit its dormant state and behave in a far more
The ability of a tumour to form blood vessels is
termed angiogenic competence and is a key feature
of malignant transformation.
Acquire the ability to invade
Cancer cells have no respect for the structure of
Cancer cells acquire the ability to breach the
basement membrane and thus gain direct access
to blood and lymph vessels.
Cancer cells use three main mechanisms to
facilitate invasion: they cause a rise in the
interstitial pressure within atissue; they secrete
enzymes that dissolve extracellular matrix; and
they acquire motility.
Acquire the ability to disseminate and implant
As soon as motile cancer cells gain access to vascular and
lymphovascular spaces, they have acquired the potential to use
the body’s natural transport mechanisms to distribute
themselves throughout the body. Distribution is not, of itself,
sufficient to cause tumours to develop at distant sites. The cells
also need to acquire the ability to implant.
Cancer cells probably implant themselves in distant tissues by
exploiting, and subverting, the normal inflammatory response.
. Cancer cells simply subvert this physiological
Cancer cells are simultaneously both ‘self’ and ‘not
Cancer cells, or at least those that give rise to clinical
disease, appear to gain the ability to escape detection
by the immune system.
This may be through suppressing the expression of
tumour-associated antigens, a stealth approach, or it
may be through actively coopting one part of the
immune system to connive in helping the tumour to
escape detection by other parts of the immune
A cancer is a genetic ferment. Cells are dividing without
proper checks and balances.
DNA is being copied, and the proofreaders have been
retired or ignored. Mutations are arising all the time
within tumours, and some of these mutations, particularly
those in tumour suppressor genes, may have the ability to
encourage the development and persistence of further
Jettison excess baggage
Cancer cells are geared to excessive and remorseless
They do not need to develop or retain those
specialised functions that make them good cellular
They can therefore afford to repress or permanently
lose those genes that control such functions.
Subvert communication to and from
Providing false information is a classic military strategy.
Degrading the command and control systems of the
enemy is an essential component of modern warfare.
Cancer cells almost certainly use similar tactics in their
battle for control over their host.
Given the complexity of communication between and
within cells, this is not an easy statement either to
disprove or to prove. Nor does it offer
any easy targets for therapeutic manipulation.
THE CAUSES OF CANCER
Both inheritance and environment are important
determinants of whether or not an individual
develops cancer. enviromental factors have been
implicated in more than 80% of cases of cancer, this
would still leave plenty of scope for the role of
genetic inheritance: not just the 20% of tumours for
which there is no clear environmental contribution
but also, as environment alone can rarely cause
cancer, the genetic contribution to the 80% of
tumours to whose occurrence environmental
As a plain example: not all smokers develop lung
cancer; lung cancer can occur in people who have
never smoked.Although environ-
One widely held opinion is that cancer is a genetic disease
that arises from an accumulation of mutations that leads to
the selection of cells with increasingly aggressive behavior.
These mutations may lead either to a gain of function by
oncogenes or to a loss of function by tumor-suppressor
genes. Most mutations in cancer are somatic and are found
only in the cancer cells.
A few of these hereditary cancer genes are oncogenes, but
most are tumor-suppressor genes. Although hereditary
cancer syndromes are rare, somatic mutations that occur in
sporadic cancer have been found to disrupt the cellular
pathways altered in hereditary cancer syndromes.
Colorectal adenomas and carcinomas, duodenal and gastric
tumors, desmoids, medulloblastomas, osteomas
Breast cancer, soft tissue sarcoma, osteosarcoma, brain
tumors, adrenocortical carcinoma, Wilms' tumor, phyllodes
tumor of the breast, pancreatic cancer, leukemia
Breast cancer, ovarian cancer, colon cancer, prostate cancer17q21BRCA1
Breast cancer, ovarian cancer, colon cancer, prostate cancer,
, pancreatic cancer, gastric cancer, melanoma
Basal cell carcinoma9q22.3PTC
Retinoblastoma, sarcomas, melanoma, and malignant
neoplasms of brain and meninges
Medullary thyroid cancer, pheochromocytoma, parathyroid
Pancreatic islet cell cancer, parathyroid hyperplasia, pituitary
Currently, approximately 60 to 90% of cancers are
thought to be due to environmental factors. Chemicals
are classified into three groups based on how they
contribute to tumor formation. The first group of
chemical agents, the genotoxins, can initiate
carcinogenesis by causing a mutation. The second
group, the cocarcinogens, by themselves cannot cause
cancer but potentiate carcinogenesis by enhancing the
potency of genotoxins. The third group, tumor
promoters, enhances tumor formation when given
after exposure to genotoxins
Physical & enviromental Carcinogens
Physical carcinogenesis can occur through induction
of inflammation and cell proliferation over a period
of time or through exposure to physical agents that
induce DNA damage. Foreign bodies can cause
chronic irritation that can expose cells to
carcinogenesis due to other environmental agents.
In animal models, for example, subcutaneous
implantation of a foreign body can lead to the
development of tumors that have been attributed
to chronic irritation from the foreign objects. In
humans, clinical scenarios associated with chronic
irritation and inflammation such as chronic
nonhealing wounds, burns, and inflammatory
bowel syndrome have all been associated with an
increased risk of cancer.
Viruses may cause or increase the risk of
malignancy through several mechanisms,
including direct transformation, expression of
oncogenes that interfere with cell-cycle
checkpoints or DNA repair, expression of
cytokines or other growth factors, and alteration
of the immune system. Oncogenic viruses may
be RNA or DNA viruses. Oncogenic RNA viruses
are retroviruses and contain a reverse
H. pylori infection is associated with gastritis
and gastric cancer, and thus its carcinogenicity
may be considered physical carcinogenesis.
Infection with the liver fluke Opisthorchis
viverrini similarly leads to local inflammation
Associated tumorInfectious agents
Stomach cancerHelicobacter pylori
Burkitt's lymphoma Hodgkin's disease Sinonasal
angiocentric T-cell lymphoma Nasopharyngeal carcinoma
16 and 18
Adult T-cell leukemia/lymphomaHuman T-cell
Classification of tumuors
1- Behavioral classification: benign or malignant
2- Histogentic classification: cell of origin
Rapidly growingSlow growing
High mitotic activityLow mitotic activity
Differs from parent tissuesResemble parent tissue
Abnormal cellsCells normal
Frequently metastatasizedNever metastasizes
Often poorly defined or irregularOften encapsulated
Ulcerating skin or mucosaRarely ulcerated
Necrosis is commenRarely undergoes necrosis
Fatal if intreatedOnly fatal when damaging vital organs
Classification by cell of origin: epithelial,
connective tissues or lymphoid or haemopeotic
Histologically determined : well differentiated,
poorly differentiated or moderately
Loss of differentiation, disorder of growth
pattern,variability of cell size, variability in
nuclear size, high nuclear/cytoplasmic ratio,
increazed mitotic activity, abnormal chromatin,
and abnormal nucleoli or multiple.
Behavior of Tumors
Invasion : is the most criteria of malignancy
spread in direct continuation.
Metastasises : is the process of malignant tumor
to spread from primary site to secondary site in
indirect continuation. By:
Or direct implantation in surgical incision
Clinical effects of tumours
Pressure on adjacent structure
Enlarged lymph nodes
Fit or confusion
These are not related to presence of tumor or
metastasises. They can divided into:
1- humoral: like Cushing’s syndrome,
inappropriate secretion of ADH, hypercalcemia,
2- immunological: autoimmune disease
triggered by malignancy like membranous
glomerulonephritis and dermatocytis.
These are caused by hormones directly secreted
by tumour like thyrotoxicosis from thyroid
adenoma insulin by insulinoma,
hyperparathyroidism by parathyroid adenoma.
Tumor markers are substances that can be detected in
higher than normal amounts in the serum, urine, or tissues
of patients with certain types of cancer. Tumors markers are
produced either by the cancer cells themselves or by the
body in a response to the cancer.
Over the past decade, there has been an especially high
interest in identifying tissue tumor markers that can be
used as prognostic or predictive markers. Although the
terms prognostic marker and predictive marker are
sometimes used interchangeably, the term prognostic
marker generally is used to describe molecular markers that
predict disease-free survival, disease-specific survival, and
overall survival, whereas the term predictive marker often
is used in the context of predicting response to certain
THE MANAGEMENT OF CANCER
Management is more than treatment
The traditional approach to cancer concentrates on
diagnosis and active treatment. This is a very limited view
and one that, in terms of the public health, may not have
served society particularly Well.
The management of cancer can be considered as taking
place along two axes: one is an axis of scale, from the
individual to the world population; the other is an axis
based on the unnatural history of the disease, from
prevention through to rehabilitation or palliative care.
Screening involves the detection of disease in an
asymptomatic population in order to improve
outcomes by early diagnosis.
It follows that a successful screening programme must
achieve early diagnosis, and that the disease in
question has a better outcome when treated at an
Criteria for screening
■ Recognisable early stage
■ Treatment at an early stage more effective than at a later stage
■ Sufficiently common to warrant screening
■ Sensitive and specific
■ Acceptable to the screened population
■ Adequate diagnostic facilities for those with a positive test
■ High-quality treatment for screen-detected disease to minimise
morbidity and mortality
■ Screening repeated at intervals if the disease is of insidious onset
■ Benefit must outweigh physical and psychological harm
at age 20
Every 3 y, ages 20–
Annual, starting at
Annual, starting at
Offer PSA test and
starting at age 50,
for men who have
life expectancy of
at least 10 y
Men aged ≥50 yprostate
Diagnosis and classification
Accurate diagnosis is the key to the successful management
of cancer. The definitive diagnosis of solid tumors usually is
obtained by performing a biopsy of the lesion. Biopsy
findings determine the tumor histology and grade and thus
assist in definitive therapeutic planning. When a biopsy has
been performed at an outside institution, the slides should
be reviewed to confirm the outside diagnosis.
Biopsy specimens of mucosal lesions usually are obtained
endoscopically (e.g., via colonoscope, bronchoscope, or
cystoscope). Lesions that are easily palpable, such as those
of the skin, can either be excised or sampled by punch
biopsy. Deep-seated lesions can be localized with computed
tomographic (CT) scan or ultrasound guidance for biopsy.
Different tumours are classified in different
ways: most squamous epithelial tumours are
simply classed as well (G1), moderate (G2) or
poorly (G3) differentiated . Adenocarcinomas
are also often classified as G1, 2 or 3,
Investigation and staging
It is not sufficient simply to know what a cancer is; it is
imperative to know its site and extent. Staging is the
process whereby the extent of disease is mapped out.
Formerly, staging was a fairly crude process based on
clinical examination and chest X-ray and the occasional
ultrasound; nowadays, it is a highly sophisticated process,
heavily reliant on the technology of modern imaging. The
International Union against Cancer (UICC) is responsible
for the TNM (tumour, nodes, metastases) staging system for
cancer. This system is compatible with, and relates to, the
American Cancer Society (AJCC) system for stage grouping
Staging of colorectal cancer
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Intraepithelial or intramucosal carcinoma
T1 Tumour invades submucosa
T2 Tumour invades muscularis propria
T3 Tumour invades through the muscularis propria
into the subserosa or into retroperitoneal (pericolic
or perirectal) tissues.
T4 Tumour directly invades beyond bowel.
NX Regional lymph nodes cannot be assessed
N0 No metastases in regional nodes
N1 Metastases in 1–3 regional lymph nodes
N2 Metastases in ≥ 4 regional lymph nodes
MX Not possible to assess the presence of
M0 No distant metastases
M1 Distant metastases present
Therapeutic decision making and the
As the management of cancer becomes more complex,
it becomes impossible for any individual clinician to
have the intellectual and technical competence that is
necessary to manage all the patients presenting with a
particular type of tumour.
The era of feigned omniscience is past. The formation
of multidisciplinary teams represents an attempt to
make certain that each and every patient with a
particular type of cancer is managed appropriately.
Teams should not only be multidisciplinary, they should
Members of the multiprofessional team
■ Site-specialist surgeon
■ Surgical oncologist
■ Plastic and reconstructive surgeon
■ Clinical oncologist/radiotherapist
■ Medical oncologist
■ Diagnostic radiologist
■ Speech therapist
■ Clinical nurse specialist (rehabilitation, supportive care)
■ Palliative care nurse (symptom control, palliation)
■ Social worker/counsellor
■ Medical secretary/administrator
■ Audit and information coordinator
Principles of cancer surgery
For most solid tumours, surgery remains the
definitive treatment and the only realistic hope
However, surgery has several roles in cancer
treatment including diagnosis, removal of
primary disease, removal of metastatic disease,
palliation, prevention and reconstruction.
Diagnosis and staging
Removal of primary disease
Radical surgery for cancer involves removal of the
primary tumour and as much of the surrounding tissue
and lymph node drainage as possible in order not only to
ensure local control but also to prevent spread of the
tumour through the lymphatics.,
Removal of metastatic disease
In certain circumstances, surgery for metastatic
disease may be appropriate. This is particularly
true for liver metastases arising from colorectal
cancer where successful resection of all
detectable disease can lead to long-term
survival in about one-third of patients.
In many cases, surgery is not appropriate for cure but may be
extremely valuable for palliation. A good example of this is the
patient with a symptomatic primary tumour who also has distant
metastases. In this case, removal of the primary may increase
the patient’s quality of life but will have little effect on the
Other examples include bypass procedures such as an
ileotransverse anastomosis to alleviate symptoms of obstruction
caused by an inoperable caecal cancer or bypassing an
unresectable carcinoma at the head of the pancreas by
cholecysto- or choledochojejunostomy to alleviate jaundice.
Principles of the non-surgical
treatment of cancer
In patients with documented distant metastatic disease,
chemotherapy is usually the primary modality of therapy. The
goal of therapy in this setting is to decrease the tumor burden,
thus prolonging survival. It is rare to achieve cure with
chemotherapy for metastatic disease for most solid tumors.
Chemotherapy administered to a patient who is at high risk for
distant recurrence but has no evidence of distant disease is
referred to as adjuvant chemotherapy.
The goal of adjuvant chemotherapy is eradication of
micrometastatic disease, with the intent of decreasing relapse
rates and improving survival rates.
Adjuvant therapy can be administered after surgery
(postoperative chemotherapy) or before surgery (preoperative
chemotherapy, neoadjuvant chemotherapy, or induction
Some tumors, most notably breast and prostate cancers,
originate from tissues whose growth is under hormonal
control. The first attempts at hormonal therapy were
through surgical ablation of the organ producing the
hormones involved, such as oophorectomy for breast
cancer. Currently, hormonal anticancer agents include
androgens, antiandrogens, antiestrogens, estrogens,
glucocorticoids, gonadotropin inhibitors, progestins,
aromatase inhibitors, and somatostatin analogues.
Hormones or hormone-like agents can be administered to
inhibit tumor growth by blocking or antagonizing the
naturally occurring substance, such as with the estrogen
antagonist tamoxifen. Other substances that block the
synthesis of the natural hormone can be administered as
Over the past decade, increased understanding of
cancer biology has fostered the emerging field of
molecular therapeutics. The basic principle of
molecular therapeutics is to exploit the molecular
differences between normal cells and cancer cells to
develop targeted therapies. Thus targeted therapies
usually are directed at the processes involved in tumor
growth rather than directly targeting the tumor cells.
The aim of immunotherapy is to induce or potentiate
inherent antitumor immunity that can destroy cancer
cells. Central to the process of antitumor immunity is
the ability of the immune system to recognize tumor-
associated antigens present on human cancers and to
direct cytotoxic responses through humoral or T-cell–
mediated immunity. Overall, T-cell–mediated immunity
appears to have the greater potential of the two for
eradicating tumor cells. T cells recognize antigens on
the surfaces of target cells as small peptides presented
by class I and class II MHC molecules
Gene therapy is being pursued as a possible approach
to modifying the genetic program of cancer cells as well
as treating metabolic diseases. The field of cancer gene
therapy uses a variety of strategies, ranging from
replacement of mutated or deleted tumor-suppressor
genes to enhancement of immune responses to cancer
cells. Indeed, in preclinical models, approaches such as
replacement of tumor-suppressor genes leads to
growth arrest or apoptosis. However, the translation of
these findings into clinically useful tools presents
Ionizing radiation is energy strong enough to remove an
orbital electron from an atom.
Radiation deposition results in DNA damage manifested
by single- and double-strand breaks in the sugar
phosphate backbone of the DNA molecule.
Cross-linking between the DNA strands and
chromosomal proteins also occurs. The mechanism of
DNA damage differs by the type of radiation delivered.
Electromagnetic radiation is indirectly ionizing through
short-lived hydroxyl radicals produced primarily by the
ionization of cellular hydrogen peroxide (H2O2).
Protons and other heavy particles are directly ionizing
and directly damage DNA.