Colorectal carcinoma Medical Assignment Help

Adenocarcinoma of the large bowel is the second commonest tumour in the UK with a lifetime incidence of about 1 in 50 (both male and female). The incidence increases with age, the average age at diagnosis being 60-65 years. The disease is rare in Africa and Asia and this difference is thought to be largely environmental rather than racial. There is a correlation between the consumption of meat and animal fat and colonic cancer. Western diets are low  in fibre and the resulting intestinal stasis increases the time for which any potential carcinogen is in contact with the bowel wall. The bacterial flora in the colon is also affected by different diets, particularly in amount of fibre present, and it is speculated that certain bacteria convert bile acids to potential carcinogens. Ulcerative colitis and FAP are predisposing factors.

A genetic model for colorectal tumorigenesis. FAP, familial adenomatous polyposis (or adenomatous polyposis coli-APe); DCC, deleted in colon cancer. (From E. R. Fearon and B. Vogelstein (1990) eel/61, 759. With permission.)

A genetic model for colorectal tumorigenesis. FAP, familial adenomatous polyposis (or adenomatous polyposis coli-APe); DCC, deleted in colon cancer. (From E. R. Fearon and B. Vogelstein (1990) eel/61, 759. With permission.)

GENETIC INHERITANCE

The development of colon cancer is now felt to involve multiple genetic alterations which occur in a stepwise fashion. The widespread recognition of the adenoma-carcinoma sequence and the identification of many molecular genetic abnormalities has led to the development of a molecular model for colon cancer tumorigenesis . The changes include the activation of dominantly acting proto-oncogenes and the inactivation of recessive tumour suppressive genes. Oncogenes, many of which have a physiological role in the regulation of normal cell division and differentiation, may result in inappropriate stimulation signals. Those most commonly associated with colon cancer are c-KRAS and c-MYC which are overexpressed in up to 50% and 70% of colon tumours respectively. Other less frequently altered oncogenes include c-SRC, c-MYB and c-ERB-2. Tumour suppressor genes conversely inhibit cell proliferation and tumorigenesis.
Mutations of the ape gene located on the long arm of chromosome 5 is responsible for the FAP syndrome, but also plays a role in sporadic colon cancer. It appears, however, that the accumulation rather than the order of changes is most important in tumour development.

Cancer families

There is a two to three times increased lifetime risk of developing colon cancer with one first-degree affected family member. Hereditary non-polyposis colon cancer (HNPCC) occurs in 5-10% of colorectal cancers. The putative gene responsible has recently been localized on chromosome 2. These patients have tumours at an early age and, more commonly, in the right colon. Many of these patients also have a high risk of endometrial and other non-gastrointestinal cancers (Lynch type II) whilst others are colon specific (Lynch type I).

Screening

The case for universal faecal occult blood screening has been made with a reduction of the 13-year cumulative mortality by 33%. It is not yet recommended in the UK. A single, flexible sigmoidoscopy at the age of 55 years or over is being recommended by some as another screening method. Universal colonoscopic screening has not shown any benefit, but colonoscopy should be performed in anyone with a history of cancer in their first- and seconddegree relatives. Measurement of DNA in the stools is also being developed for screening.

PATHOLOGY

Two-thirds of carcinomas occur in the rectosigmoid area. The tumour, which is usually a polypoid mass with ulceration, spreads by direct infiltration through the bowel wall. It then invades the lymphatics and blood vessels with early spread to the liver. Widespread metastases, e.g. to the lung, can occur. Synchronous tumours are present in 2% of cases.

CLINICAL FEATURES

Alteration in bowel habit, with or without abdominal pain, is a common symptom of left-sided colonic lesions. Rectum and sigmoid carcinomas usually bleed, blood being mixed in with the stool. Carcinoma of the caecum may become large and still remain asymptomatic. It can present simply as an iron deficiency anaemia. The elderly often present with intestinal obstruction. Any change in bowel habit or bleeding per rectum must be investigated, particularly in the older age group.
Clinical examination is usually unhelpful, but a mass may be palpable. With liver metastases, hepatomegaly is found. Digital examination of the rectum is essential and sigmoidoscopy should be performed in all cases. Fibreoptic sigmoidoscopy can be performed on an outpatient basis after a single enema and increases, by three to four times, the extent of the colon seen covering the area with the highest risk of carcinoma.

INVESTIGATION

A BLOOD COUNT and routine biochemistry are performed.
A DOUBLE-CONTRAST BARIUM ENEMA is still the investigation of choice but good preparation to ensure that the colon is free of faeces is essential.

COLONOSCOPY is used for confirmation of doubtful lesions and to obtain specimens for histological examination.
OCCULT BLOOD TESTS have been used for mass screening but are of no value in hospital practice.
ULTRASOUND. Evaluation of secondary spread is performed prior to surgery with abdominal ultrasound and rectal ultrasound, which is valuable to indicate tumour size and local spread.

Classification of colorectal carcinoma showing the percentage of cases that are resected and their life prognosis. NB. Approximately 20% of the cases at presentation of colorectal carcinoma are inoperable. Of those submitted to surgery the findings are shown in the table.

Classification of colorectal carcinoma showing the percentage of cases that are resected and their life prognosis. NB. Approximately 20% of the cases at presentation of colorectal carcinoma are inoperable. Of those submitted to surgery the findings are shown in the table.

TREATMENT

This is surgical, with resection and end-to-end anastomosis if possible. Anastomosis is now possible with all but the most distal rectal carcinomas, when colostomy is necessary. The 5-year survival rate is 30% overall, but in tumours confined to the bowel wall (i.e. not reaching the serosa-Dukes’ grade A), the 5-year survival is over 95% . Adjuvant chemotherapy increases survival in Dukes’ grade Band C. Adjuvant chemotherapy and radiotherapy increase survival in grade C rectal carcinoma. Chemotherapy is sometimes used when metastases are present, but results are poor.

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Gastroenterology

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