Cancer that effects either the colon or rectum is termed as colorectal malignant neoplastic disease ( CRC ) . Worldwide, CRC is the 2nd most common malignance and is a taking cause of cancer-associated decease in many developed states. The incidence of CRC is high in parts such as North America, Western and Eastern Europe, Japan, Israel, Singapore, Australia and New Zealand.
In add-on to this CRC is rather prevailing in some countries of Brazil, Argentina, Hong Kong, Southern China and Malaysia ( Rozen et al. , 2006 ) . In Singapore, CRC is the taking malignant neoplastic disease in males and the 2nd most common malignant neoplastic disease in females, accounting for 17.9 % of all malignant neoplastic diseases in males and 14.4 % in females. When both genders are combined, CRC is the most common malignant neoplastic disease in Singapore.
The age-standardized rate ( ASR ) for mortality from CRC in Singapore over the period from 2002 to 2006 was 18.1 per 100,000 per twelvemonth in males and 12.5 in females ( Tey et al.
, 2008 ) . The ASR for CRC mortality rates in the United States and United Kingdom in 2002 harmonizing to the World Health Organization ( WHO ) were 14.8 and 17.3 per 100,000 per twelvemonth, severally ( hypertext transfer protocol: //www.who.int/healthinfo ) .
Certainly CRC has emerged as a serious menace to public wellness both locally every bit good as worldwide.
Etiology of colorectal malignant neoplastic disease
On the footing of etiology CRC can be inherited, inflammatory or sporadic in nature. Lynch syndrome is the most common familial syndrome that predisposes patients to CRC, followed by familial adenomatous polyposis coli ( FAP ) . Although the footings Lynch syndrome and familial nonpolyposis colorectal malignant neoplastic disease ( HNPCC ) are frequently used synonymously HNPCC specifically refers to those upsets that have similar phenotypes but lack the specific mutants involved in Lynch syndrome. Lynch syndrome and HNPCC together accounts for 2-5 % of all CRC. This signifier of heritable CRC is characterized by early oncoming and preponderantly right-sided mucinous tumour.
Germline mutants in the mismatch fix ( MMR ) cistrons viz. MLH1 and MSH2 characterized by reproduction mistake and hence Deoxyribonucleic acid or microsatellite instability ( MSI ) , comprises the major familial defect doing HNPCC or Lynch syndrome. Apart from CRC, HNPCC or Lynch syndrome besides predisposes patients to other extra-colonic malignant neoplastic diseases such as small-intestine, nephritic pelvic girdle and endometrial malignant neoplastic disease ( Lindor et al. , 2005 ; Lynch et al. , 2009 ) .
FAP which is responsible for less than 1 % of all CRC instances occurs due to a mutant in the adenomatous polyposis coli ( APC ) cistron. Development of 100s to 1000s of adenomatous polyps in the colon and rectum of persons get downing from early adolescence, which necessarily leads to CRC if untreated, is the chief feature of FAP. FAP besides leads to assorted extra-colonic manifestations like thyroid malignant neoplastic disease, duodenal and fundic secretory organ polyposis and desmoids ( Jasperson et al. , 2010 ) . Inflammatory intestine disease ( IBD ) including Crohn ‘s disease ( Cadmium ) and ulcerative inflammatory bowel disease may besides take to CRC. However patients with IBD represent merely 1-2 % of CRC instances. The hazard of CRC is much higher in persons holding prolonged ( more than 30 old ages ) and extended ulcerative inflammatory bowel disease ( Lakatos and Lakatos, 2008 ; Kraus and Arber, 2009 ) . Majority of CRC ( upto 80 % ) is sporadic in nature with no well defined etiology and occurs due to interaction between familial and environmental factors ( Cheah, 1990 ) .
Ageing is one of the major hazard factors for sporadic CRC as 99 % of instances occur in people more than 40 old ages of age and 85 % in those more than 60 old ages of age. Higher incidence of CRC in flush societies is related to lifestyle related factors such as high consumption of fat and ruddy meat, deficient consumption of fibre rich nutrient and veggies, fleshiness and low physical activity. High intoxicant ingestion, diabetes mellitus and smoke besides increase the hazard of CRC ( Ballinger and Anggiansah, 2007 ; Cunningham et al. , 2010 ) .
1.3. Diagnosis of colorectal malignant neoplastic disease
CRC if diagnosed at an early phase improves opportunities of endurance of patient and reduces treatment-related morbidity.
An person may be diagnosed with CRC when he or she presents certain symptoms or as a consequence of any screening plan. Normally early phase of CRC does non bring forth any noticeable symptoms. Furthermore most of the symptoms of CRC for case alteration in intestine wonts, blood in stool, general uncomfortableness in the venters, weight loss, fatigue, deficiency specificity. Therefore it is indispensable to transport out regular testing plans to observe CRC. Endoscopy utilizing either flexible sigmoidoscopy or colonoscopy with tumour biopsy is the most common diagnostic method for CRC. However these techniques require extended intestine readying and lacks patient conformity due to their invasive nature.
Double contrast Ba clyster ( DCBE ) is used as an accessory diagnostic technique particularly to observe tumors or polyps in Byzantine anatomical sites where endoscopic survey is hard to transport out. Although fecal supernatural blood trial ( FOBT ) for CRC diagnosing is simple and non invasive in nature, it lacks specificity. Faecal DNA based trial is more sensitive than FOBT but it is boring to administrate and expensive.
Computed tomographic ( CT ) colonography, besides termed as practical colonoscopy, is a non invasive diagnostic technique that produces two- and 3-dimensional images of the colorectal piece of land. CT colonography is peculiarly utile in placing polyps or colonic lesions that are non detected by colonoscopy. CT and magnetic resonance imagination ( MRI ) are besides used to observe extent of disease in patients with suspected liver metastases from CRC. Of the assorted serum-based markers for CRC that have been investigated, carcino-embryonic antigen ( CEA ) has been found to be utile for preoperative theatrical production and follow up. However, CEA is non recommended for diagnosing because of its low sensitiveness and specificity. Familial trials are required for showing of heritable signifiers of CRC like HNPCC and FAP ( Cunningham et al. , 2010 ; Labianca et al.
, 2010 ) .
Theatrical production of colorectal malignant neoplastic disease
The Duke ‘s categorization ( Duke, 1932 ; Weiss, 2000 ) and the TNM ( tumour, node, metastases ) system ( Fleming et al. , 1997 ) are the two most common presenting systems for CRC. The other less normally used theatrical production system is the modified Astler Coller ( MAC ) system ( Astler and Coller, 1954 ; Gunderson and Sosin, 1974 ) .
The TNM system is chiefly based on the size and grade of invasion of the primary tumor ( T ) , extent of lymph node engagement ( N ) and grade of metastasis ( M ) . It was introduced by the American Joint Committee on Cancer ( AJCC ) and the most preferable system of theatrical production of CRC. The TNM system and AJCC phase groupings with tantamount Duke ‘s and MAC phases of CRC have been summarized in Table 1.1. The TNM system encompasses both clinical ( pretreatment ) and a pathological ( postsurgical histopathological ) theatrical production. The clinical classii¬?cation is designated as cTNM and the histopathological categorization is designated as pTNM.
Normally the cTNM is used to choose intervention regimen whereas the pTNM is used for forecast of CRC. Preoperative presenting involves appraisal of patient ‘s medical history, physical scrutiny for megalohepatia, ascites, lymphadenopathy, rating of blood count, CEA and liver chemical sciences, scrutiny of big bowel utilizing endoscopic techniques or CT or MRI. Surgical theatrical production of CRC involves an rating of extra-colonic metastases, nodal spread and grade of tumor invasion through the colonic wall and onto environing constructions ( Labianca et al. , 2010 ) .
5. Prognosis of colorectal malignant neoplastic disease
Extent of incursion of tumour through the colonic wall and the engagement of lymph nodes, are of import predictive factors of CRC. Other pertinent predictive parametric quantities include tumour class, thymidine labelling index, vascular and perineural invasion and lymphoid inflammatory response. Grading of CRC tumours is carried out on the footing of histopathological parametric quantities such as histologic type, quality of distinction, mutual opposition of karyon, coni¬?guration of tubules, growing form, lymphocytic ini¬?ltration and extent of i¬?brosis. At nowadays a three class system is most widely used.
Well differentiated tumours with good formed tubules and demoing least atomic polymorphism and mitoses are termed as class 1. Ill differentiated tumours with rare glandular signifiers, multistructural cells and a high extent of mitoses are termed as Grade 3. Tumors intermediate between classs 1 and 3 are considered as grade 2. Rate 1 tumours are the least aggressive and the 5-year endurance rate ( YSR ) is 59-93 % . In instance of class 2 and 3 tumours the 5-YSR falls to 33-75 % and 11-56 % severally ( Jass et al. , 1986 ; Qizilbash, 1982 ) .
The clinical public-service corporation of assorted other predictive indexs like look of protein 53 ( p53 ) , B-cell lymphoma 2 ( bcl-2 ) , tumor growing factor alpha ( TGF-? ) , cuticular growing factor ( EGF ) , transforming growing factor-beta receptor II cistron ( TGFBR2 ) , deleted in colorectal malignant neoplastic disease ( DCC ) cistron, thymidylate synthase ( TS ) , V-Ki-ras2 Kirsten rat sarcoma viral transforming gene homolog ( KRAS ) mutants, MSI position, allelomorphic loss of chromosome 18q tissue have been investigated. Although 18q omission and MSI position have shown promise their practical public-service corporation still remains to be confirmed by big graduated table surveies ( Deans et al. , 1992 ; Steinberg et al. , 1987 ; Sternberg et al.
, 1999 ) . Location of CRC tumour is besides a good index of forecast for case left sided lesions favours patient endurance whereas right sided tumours particularly those doing intestine obstructor reduces opportunities of endurance ( Wolmark et al. , 1983 ) .
Presence of perforation in the colonic piece of land indicates negative forecast ( Steinberg et al. , 1987 ) . Increased pre-treatment degrees of serological markers like saccharide antigen 19-9 ( CA 19-9 ) and CEA are associated with hapless forecast ( Filella et al. , 1992 ) . CRC patients who respond to chemotherapy with drugs like 5-i¬‚uorouracil ( 5-FU ) , irinotecan and oxaliplatin have longer average endurance clip than non-responders.
Response to chemotherapy and opportunities of endurance in instances of metastatic CRC are dependent on the extent of metastasis which can be evaluated by finding the figure of sites to which metastasis has occurred, figure of lesions in such sites and the extent to which the liver is affected. Generally female patients have better endurance clip than male patients. Patients demoing no symptoms of CRC exhibit better response to chemotherapy and survive longer than those demoing symptoms. Prior chemotherapy consequences in opposition to second-line intervention ( Buyse et al.
, 2000a, 2000b ; Kohne et al. , 2002 ) .