Oncology and surgical practice
Oncology and surgical practiceBy Dr. Thaere JasimGeneral surgeonTikrit University college of medicineoncology 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. Malignant transformation Establish an autonomous lineageResist signals that inhibit growthAcquire 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 theenvironment/milieuHallmarks of Cancer
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.
Obtain immortalitynormal 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 out.Evade apoptosisApoptosis 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 development.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 transformation. 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 competenceA mass of tumour cells cannot, in the absence of a blood supply, grow beyond a diameter of about 1mm. 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 aggressive fashion. 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 invadeCancer cells have no respect for the structure of normal tissues.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 implantAs soon as motile cancer cells gain access to vascular and lymphovascular spaces, they have acquired the potential to use the bodys 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 mechanism.Evade detection/eliminationCancer cells are simultaneously both self and not self. 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 surveillance systemGenomic instabilityA 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 timewithin tumours, and some of these mutations, particularly those in tumour suppressor genes, may have the ability to encourage the development and persistence of further mutationsJettison excess baggageCancer cells are geared to excessive and remorseless proliferation.They do not need to develop or retain those specialised functions that make them good cellular citizens. They can therefore afford to repress or permanently lose those genes that control such functions.Subvert communication to and from the environment/milieuProviding 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 offerany easy targets for therapeutic manipulation.THE CAUSES OF CANCERBoth 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% oftumours to whose occurrence environmental factors contribute.As a plain example: not all smokers develop lung cancer; lung cancer can occur in people who have never smoked.Although environ-Genetic Chemical CarcinogensPhysical CarcinogensViral CarcinogensBacteria, fungi, parasiteHormonesOthers agents
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.Cancer siteLocation Gene Colorectal adenomas and carcinomas, duodenal and gastric tumors, desmoids, medulloblastomas, osteomas17q21APCBreast cancer, soft tissue sarcoma, osteosarcoma, brain tumors, adrenocortical carcinoma, Wilms' tumor, phyllodes tumor of the breast, pancreatic cancer, leukemia17p13p53Breast cancer, ovarian cancer, colon cancer, prostate cancer17q21BRCA1Breast cancer, ovarian cancer, colon cancer, prostate cancer, , pancreatic cancer, gastric cancer, melanoma13q12.3BRCA2Basal cell carcinoma9q22.3PTCRetinoblastoma, sarcomas, melanoma, and malignant neoplasms of brain and meninges13q14rbMedullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia10q11.2RETPancreatic islet cell cancer, parathyroid hyperplasia, pituitary adenomas11q13MEN1Chemical Carcinogens
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 genotoxinsPredominant Tumor ChemicalLung cancer, oral cancer, pharyngeal cancer, laryngeal cancer, esophageal cancer (squamous cell), pancreatic cancer, bladder cancer, liver cancer, renal cell carcinoma, cervical cancer, leukemiaTobacco smokeLiver cancerAflatoxinsLeukemiaBenzeneBladder cancerBenzidineSkin cancer, scrotal cancerCoal tarLeukemia, lymphomaEthylene oxideLung cancer, nasal cancerNickelAngiosarcoma of the liver, hepatocellular carcinoma, brain tumors,Vinyl chlorideOral cancerTobacco products, smokelessPhysical & 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.Associated tumourPhysical agentsSkin tumourUV exposureLeukaemia Breast Lymph