Any type of disease characterised by the uncontrolled proliferation of unnatural cells that grow beyond their natural boundary lines is termed malignant neoplastic disease by the World Health Organisation. These cells can impact any tissue of the organic structure, invade environing 1s and even make other variety meats, through a procedure called metastasis. The term “ malignant neoplastic disease ” is frequently used interchangeably with the term “ malignant neoplasia ” which consists of fast turning ill differentiated cells occupying and destructing tissues of their immediate surrounding and metastasizing in other countries of the human organic structure thereby shortening the life span of the patient, an illustration being breast glandular cancer.
One of the most important demographic alterations of the twenty-first century is the aging population. “ The ripening procedure is of class a biological world which has its ain moral force, mostly beyond human control. However, it is besides capable to the buildings by which each society makes sense of old age. In the developed universe, chronological clip plays a paramount function. The age of 60 or 65, approximately tantamount to retirement ages in most developed states, when they secure their pension entitlement, is said to be the beginning of old age. ” ( Gorman, 1999 )
Cancer is a world-wide disease common to people of all age-groups ( Administration on Aging, 2000 ) . Cancer was the taking cause of freshly diagnosed disease and decease in 2008 with an estimated 12.7 million new instances and 7.6 million decease worldwide ( Ferlay, 2010 ) . However, incidence and mortality rates are highest in individuals aged 60 old ages and above ( Wedding, 2007 ) therefore impacting the aged population to a greater extent than the younger population. There are a figure of possible grounds to explicate these findings in the elderly population, some of which suggest a considerable sum of familial harm to cells that has built up over clip and an drawn-out exposure to cancer-causing substances over the old ages ( Taylor and Kuchel, 2009 ) .
By the twelvemonth 2050, the Mauritanian aged population is expected to treble to about 371 000 ( Suntoo, 2012 ) . With the enlargement of this age group, the absolute figure of older persons diagnosed with malignant neoplastic disease in future decennaries will doubtless increase and this state of affairs presents itself as a major challenge for medical professionals.
EPIDEMIOLOGY OF CANCER IN THE ELDERLY
In the United States, 60 % of all freshly diagnosed malignant neoplastic disease patients and 70 % of all malignant neoplastic disease deceases occur in the aged population ( Rao et al. , 2008 ) . Harmonizing to the National Cancer Registry of the Republic of Mauritius, 40 % of all new instances of malignant neoplastic disease registered for the period 2005-2008 occurred in the aged ( 55 % in males and 41 % in females ) . The incidence of malignant neoplastic disease amongst the aged is estimated to lift by about one tierce over the following three decennaries ( Ferlay, 1999 ) .
Following statistics from Cancer Research UK for the twelvemonth 2005-2008, 53 % of all malignant neoplastic diseases were diagnosed in patients aged between 50 and 74 old ages of age with somewhat more instances in males ( an norm of 88,198 per twelvemonth ) than in females ( 78,240 ) and 36 % of all new malignant neoplastic diseases were diagnosed in patients aged 75 old ages and supra.
In the UK, for the period 2007-2009, malignant neoplastic disease was responsible for 40 % of deceases in the 50-74 twelvemonth olds and 26 % of deceases in those aged 75 old ages and older for males while 47 % of females above 50 old ages old and 18 % of females above 75 old ages died of malignant neoplastic disease harmonizing to Cancer Research UK.
PATHOGENESIS OF CANCER
Cancer cells are formed when the familial stuff or Deoxyribonucleic acid ( deoxyribonucleic acid ) within the normal cell nucleus gets damaged. Deoxyribonucleic acid is responsible for all cellular activities: growing, decease, protein synthesis etc. When Deoxyribonucleic acid is damaged, the cell normally either mend the harm or dies. In malignant neoplastic disease cells, nevertheless, neither is the damaged Deoxyribonucleic acid repaired, nor does the cell dice. Alternatively it starts multiplying to give more of such unnatural cells with damaged DNA. Genomic harm may be inherited from parents or may be the consequence of exposure to certain cancer-causing agents.
THE NORMAL CELL CYCLE
The normal cell rhythm consists of 4 chief phases: G1, S, G2 and M and represents all structural alterations that occur in a cell for mitosis to happen. G1 is the first spread after proliferative stimulation but if the cell is meant to split, so there are biochemical reactions which occur in G1 to fix the cell for reproduction. The S stage is for DNA synthesis and chromosome reproduction. G2 is the 2nd spread after DNA synthesis. M refers to mitosis phase taking to the dislocation of atomic membrane and cytokinesis to bring forth two girl cells. The last phase G0 involves non-cycling cells in a resting province with G1 DNA. There are besides three major checkpoints during the cell rhythm: The G1 checkpoint ensures that adequate foods are available to back up the ensuing girl cells ; The G2 checkpoint ensures that DNA reproduction in S stage has been completed successfully ; The metaphase checkpoint ensures that all of the chromosomes are attached to the mitotic spindle by a centromere.
When a normal human cell becomes cancerous, this transmutation is termed cancerogenesis. Cancerogenesis occurs because of harm to the familial stuff of the cell upon exposure to carcinogens but this exposure does non instantly lead to malignance. The procedure of malignant transmutation is divided into three major stairss:
The first phase – INITIATION involves rapid and irreversible DNA lesion which occurs when a normal human cell encounters a carcinogen. Throughout the induction, the chief alterations in cell-regulating mechanisms that occur include proto-oncogenes which code for normal cell growing are converted to transforming genes which cause uncontrolled growing stimulation ; Tumour suppresser cistrons which normally regulate cell proliferation get deactivated ; Genome fix mechanisms responsible for testing the Deoxyribonucleic acid for defects and reconstructing it are non-functioning ; Apoptosis regulation mechanisms which cause car devastation of faulty cells are inactive.
The 2nd phase – Promotion refers to the drawn-out exposure to substances ( tumour boosters ) which are non straight carcinogenic in their ain right but maintain and brace the initiated lesion ) . During this measure, tumour boosters contribute to carcinogenesis by triping intracellular signalling tracts to chiefly advance clonal cell enlargement.
The concluding phase – PROGRESSION describes the advancement to malignance following farther interaction with carcinogens and tumor boosters where there is uncontrolled generation, loss of distinction, local invasion and even metastasis.
Carcinogens ( besides called mutagens ) are cancer-causing substances. There are four chief groups of carcinogens: chemicals, physical agents, viral and bacterial infections and the lone manner to distinguish between them is the manner they cause harm to the genome. For an person, the chance for developing a malignant neoplastic disease following exposure to a peculiar carcinogen depends on the manner the individual has been exposed, the length, strength, type of exposure and familial factors.
Everyday people are exposed to chemical compounds with mutagenic belongingss ( Wogan et al, 2004 ) . They are molecules which form a chemical bond with the human genome and interrupt it. There exist direct-acting physical carcinogens which are already mutagenic before being absorbed by the organic structure and indirect-acting carcinogens which get mutagenic belongingss after holding been metabolised by the organic structure. Exposure to these carcinogens can happen exogenously when they are present in nutrient and the environment, but besides endogenously when they are produced from bodily activities or pathophysiological conditions like redness ( Wogan et al, 2004 ) .
Chemical carcinogens were already described in the twelvemonth 1775 by Percival Pott who recorded the high incidence of scrotal malignant neoplastic disease amongst chimney expanses due to their changeless exposure to char pitchs. Compounds incorporating in baccy have been proved to exhibit mutagenic belongingss and cause lung malignant neoplastic disease ( Hecht, 1999 ) . Aflatoxins, produce by a cast and nowadays in dietetic supplies has been recognised to do primary liver malignances amongst Africans and Asians ( Wogan et al, 2004 ) . Heterocyclic aminoalkanes are indirect-acting mutagens produced when meats are heated above 180 grades Celsius for long periods but they must be metabolized to electrophiles in the liver before doing genomic harm.
The term “ physical carcinogens ” includes a broad scope of agents the most common being, electromagnetic UV radiations, ionizing atomic radiation and stuffs such as gels ( silicone gels in chest prosthetic devices ) , fibers ( asbestos ) and particulate stuffs ( crystalline sillica ) that initiate cancerogenesis chiefly through their physical effects on a cell, instead than through chemical interactions with the cell, compared to “ chemical carcinogens ” ( Bast et al, 2000 ) .
The mechanism of cancerogenesis associated with physical mutagens is unsure. One theory explains that the physical atoms initiate a strong inflammatory response in environing tissues followed by infiltration of the tissue with the host ‘s immune cells. The host defense mechanisms being unable to free the foreign atom, this consequences in chronic redness. While the normal tissue continues to undergo proliferation, some cells undergo neoplastic alterations. The larger surface country of the atom, the more cells able to come into contact with the atom, the more terrible is the redness and the higher is the hazard of cellular mutant. Bakelite discs initiate local fibro sarcomas ( Turner 1942 ) . Surveies have proved undeniable mutagenic belongingss of asbestos fibers on assorted human ( Landrigan, 1991 ) .
Electromagnetic and ionising radiations initiate cancerogenesis through a two-step mechanism. First, the radiation straight ionises cellular molecules. Second, the interaction with cellular H2O and O green goodss free groups which cause genomic breakage, enzyme inactivation and membrane lysis.
This category of mutagens consists of viruses, bacteriums and parasites which have been recognised to innitiate cancerogenesis after infecting the human organic structure. It has been found Hepatitis B, hepatitis C ( liver malignant neoplastic disease ) , human papillomavirus ( cervical malignant neoplastic disease ) and Helicobacter pylori ( stomach malignant neoplastic disease ) infections are responsible for up to 18 % of malignant neoplastic disease load ( Parkin, 2006 ) .
After reassigning its familial stuff to human cells for reproduction, a virus can do genomic deregulating in the host cell can happen via two mechanisms. The viral genome can either organize a stable bond with the human genome, after which it is translated into a new combined genome and from so it is involved in cellular mechanisms or it can adhere cellular proteins and impact the signal transduction for illustration Epstein-Barr virus is responsible nasopharyngeal carcinoma and Burkitt ‘s B-cell lymphoma ( Bell, 2006 ) .
Bacterial infections and parasitic infections have been found to do malignant neoplastic disease through chronic redness as in the instance of Helicobacter pylori which causes stomachic malignant neoplastic disease and Schistosoma haematobium associated associated with high incidence of vesica malignant neoplastic disease ( Botelho, 2010 ) but bacteriums besides produce mutagenic compounds as a consequence of their metabolic activities ( Parsonnet, 1995 ) .
ENDOGENOUS METABOLIC BYPRODUCTS
Normal cellular activities can besides be a cause of malignant neoplastic disease. Our organic structure metamorphosis generates a big sum of O reactive species, nitrosamines, and reactive aldehydes. Our detoxification mechanisms normally get rid of these possible carcinogens but non absolutely particularly in pathophysiological complications like chronic redness. Endogenous DNA harm occurs more often than harm by external agents but the types of harm produced by normal cellular procedures are really similar to those caused by environmental carcinogens ( Jackson and Loeb, 2001 )
CANCER RISK FACTORS
Changes in the cell which give rise to malignant neoplastic disease occur by changing grades of interaction between host factors and exogenic factors.
Host factors or endogenous factors arise within the patient ‘s organic structure. These include heredity, endocrines ( Alvarez, 1982 ) and age ( Kono, 2010 ) .
Old age is the greatest malignant neoplastic disease hazard factor ( Colditz, et al. , 2006 ) . The hazard of malignant neoplastic disease amongst the aged population is about 10 times more of import than in the younger age-group ( Yancik, 1997a ; Yancik and Ries, 2004 ) . 60 % of all malignant neoplastic diseases have been said to happen in the older age-group ( Yancik, 1997b ; Hansen, 1998 ) . These tendencies nevertheless decline in the oldest ( 90 old ages and above ) ( Agostara et al. , 2008 ) .
GENETICS AND CANCER
Patients whose household members have had malignant neoplastic disease are more likely to develop malignant neoplastic disease themselves. Direct monitoring of patients and their households indicates a familial factor in colon, chest, and ovarian malignant neoplastic diseases, to mention merely a few familiar cases. Peoples with a close relation who has had colon malignant neoplastic disease are three times every bit likely to develop it themselves as are people without such a comparative ( Ramming, 1985 ) . Women whose female parents had breast malignant neoplastic disease have three times the hazard of undertaking this unwellness as those whose female parents did non hold the disease ( Newell, 1982 ) .
Endogenous endocrines contribute to the development of malignant neoplastic disease when they are in overly high concentrations in the blood stream. Diseases known or believed to be linked to endocrines include malignant neoplastic diseases of the endometrium, chest, prostate, ovary, testicles, thyroid, and bone. The same biological procedure that promotes normal growing besides increases the hazard of malignant neoplastic disease. Hormones such as testosterone and estrogen promote the growing of tissues in specific “ mark ” variety meats, such as the prostate and the chest. An surplus of endocrines accelerates growing, with each supernumerary cell division raising the opportunity that a malignant neoplastic disease cell will be produced ( Henderson, 1982 ) . surveies have shown that adult females known to be at hazard for chest malignant neoplastic disease have elevated degrees of estrogen ( Henderson, 1975 ) and that work forces with prostate malignant neoplastic disease have elevated degrees of testosterone ( Ghanadian, 1979 ) .
1.4.2 Exogenous Agents
These are environmental and behavioral factors which increase the chance for malignant neoplastic disease to happen.
Our eating wonts have a considerable impact on our hazard to develop malignant neoplastic disease. Harmonizing to the American Institute for Cancer Research, Food, Nutrition, and the Prevention of Cancer, 375 000 new malignant neoplastic disease instances could be prevented annually through a healthy diet.
Diets incorporating significant sums of ruddy or preserved meats may increase the hazard of assorted malignant neoplastic diseases, including colorectal malignant neoplastic disease. Red meat may be associated with colorectal malignant neoplastic disease by lending to N-nitroso compound ( NOC ) exposure. Laboratory consequences have shown that meats cooked at high temperatures contain other possible mutagens in the signifier of heterocyclic aminoalkanes ( HCAs ) and polycyclic aromatic hydrocarbons ( PAHs ) ( Cross,2004 ) .
High fat content is a propable hazard factor for cancerogenesis ( Khalid, 2009 ) . The association between fat consumption and several common malignant neoplastic diseases, eg, those of the colorectum, chest, endometrium, ovary, and prostate, received its strongest support from correlativity surveies on populations ( La Vecchia, 1992 ) . Strong correlativities among states between per capita dietary fat ingestion and rates of malignant neoplastic diseases of the chest, colon, and rectum have suggested possible causal relationships ( Willett, 1998 ) .
One in 20 malignant neoplastic diseases may be linked to diets low in fruit and veggies ( Parkin, 2011 ) . More than one in 10 intestine malignant neoplastic diseases linked to a low fiber diet ( Parkin, 2011 ) . Surveies have found that people who eat the most fruit and veggies can take down their hazard of malignant neoplastic disease by about a one-fourth compared to those who eat the least ( Benetou, 2008 ) . The UK EPIC survey has found that eating tonss of fruit and veggies could cut down the hazard of oral cavity, oesophageal and lung malignant neoplastic diseases ( Boeing, 2006 ) , every bit good as some types of tummy malignant neoplastic disease ( Gonzalez, 2006 ) but have no proved consequence on the hazard of chest, prostate, ovarian or kidney malignant neoplastic diseases ( IARC, 2003 ) .
Tobacco AND ALCOHOL
1.6 EFFECTS OF TUMOUR ON PATIENT
DETECTION AND DIAGNOSIS
TUMOUR GRADING AND STAGING
Based on the microscopic visual aspect of malignant neoplastic disease cells, diagnosticians normally describe tumour class by four grades of badness: Grades 1, 2, 3, and 4. The cells of Grade 1 tumours resemble normal cells, and tend to turn and multiply easy.
The American Joint Committee on Cancer recommends the undermentioned guidelines for rating tumors:
GX Grade can non be assessed ( Undetermined class )
G1 Well-differentiated ( Low class )
G2 Reasonably differentiated ( Intermediate class )
G3 Poorly differentiated ( High class )
G4 Undifferentiated ( High class )
The TNM system is one of the most widely used presenting systems. This system has been accepted by the International Union Against Cancer ( UICC ) and the American Joint Committee on Cancer ( AJCC ) .
The TNM system is based on the extent of the tumour ( T ) , the extent of spread to the lymph nodes ( N ) , and the presence of distant metastasis ( M ) . A figure is added to each missive to bespeak the size or extent of the primary tumour and the extent of malignant neoplastic disease spread.
Primary Tumor ( T )
TX Primary tumour can non be evaluated
T0 No grounds of primary tumour
Tis Carcinoma in situ ( CIS ; unnatural cells are present but have non spread to neighbouring tissue ; although non malignant neoplastic disease, CIS may go malignant neoplastic disease and is sometimes called preinvasive malignant neoplastic disease )
T1, T2, T3, T4 Size and/or extent of the primary tumour
Regional Lymph Nodes ( N )
NX Regional lymph nodes can non be evaluated
N0 No regional lymph node engagement
N1, N2, N3 Involvement of regional lymph nodes ( figure of lymph nodes and/or extent of spread )
Distant Metastasis ( M )
MX Distant metastasis can non be evaluated
M0 No distant metastasis
M1 Distant metastasis is present