Epidemiology

Colorectal cancer is a major cause of morbidity in the West. In 2011, 41,581 people were diagnosed with colorectal cancer and 15,609 died of the disease. The incidence has risen modestly over the last quarter of a century and the 5-year overall survival has doubled over the same time interval to around 50% (Table 11.1). The introduction of screening by one-off flexible colonoscopy or faecal occult blood (FOB) testing is likely to alter the incidence and mortality over the next decade. Colorectal cancers evolve over a 10-year period from polyp to invasive cancer. It is likely that a single colonoscopy every 10 years provides effective screening and prevention, but the cost of all those endoscopies for the entire population is unaffordable and so cannot be used as a screening tool.

Pathogenesis

Consumption of both red meat and processed meat (ham, bacon, sausages, pate, tinned meat) are associated with an increased risk (Table 11.2). High fibre diets increase the transit time of the stool and decrease the colorectal epithelial exposure to carcinogens within the stool. Higher consumption of dietary fibre especially cereal fibre reduces mainly left-sided colon cancers. Overall vegetable consumption also reduces the risk, but the benefit of fruit has not been confirmed in meta-analyses despite the constant advice to eat five fruits (or vegetables) a day. This advice is not based on facts and has been conjured up by some committee, in a similar way to the alcohol consumption advisory figures. Nevertheless, the authors suggest that you do not tell young children this information as the reaction of their mothers is wholly unpredictable.

Aspirin has been shown to have a protective effect against colorectal cancer, and epidemiological studies of prolonged aspirin use have shown a consistent reduction of up to 50% in the risk of colorectal cancers. This decrease in risk is thought to be due to the inhibitory effect of aspirin on cyclooxygenase-2, which is an enzyme found in high concentrations in colorectal tissue and promotes the growth of polyps. In randomized studies, aspirin has been shown to reduce the incidence of adenomatous polyps in patients screened after the excision of a primary colorectal tumour. There has, however, only been a single randomized trial of aspirin prophylaxis, which has shown no evidence for a reduction in colorectal cancer incidence and the toxicity; especially the risk of gastrointestinal haemorrhage means that it is premature to recommend aspirin as chemoprevention. Patients with both Crohn’s disease and ulcerative colitis are at risk from developing colonic tumours, and this risk rises to over 10% after 20 years follow-up. The risk factors for colorectal cancer in patients with inflammatory bowel disease include the duration of colitis and the extent of colonic involvement.

Up to 20% of patients with colorectal cancer have a family history of colorectal cancer. There are two significant familial causes for colorectal cancer: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). FAP is an autosomal dominant condition that accounts for 1% of all colorectal cancer. The gene for FAP was mapped to chromosome 5q21 in 1987 and the responsible gene APC was cloned in 1991. All patients with FAP develop colorectal cancer by the age of 40 years, so prophylactic colectomy is offered to teenagers with FAP. HNPCC, or Lynch syndrome, is responsible for 2–5% of colorectal cancers. HNPCC is characterized by colorectal cancers occurring at an early age, and they are often sited on the right side of the colon. In addition, HNPCC is associated with endometrial carcinoma, and gastric, renal, ureteric and central nervous system malignancies. In this condition, the genetic abnormalities include microsatellite instability and mutated mismatch-repair genes (most frequently hMSH2 and hMLH1).

In the vast majority of non-inherited colorectal malignancy, the molecular changes consist of a sequential accumulation of mutations in genes including p53 and deletion of the colorectal gene (DCC), K-Ras and APC. Indeed, it was the identification by polymerase chain reaction (PCR) of a K-Ras mutation that led pathologists to confirm the cause of death of King Ferdinand I of Aragon, the King of Naples. After his death, his body was mummified and embalmed in 1494 and placed in a wooden sarcophagus at the Abbey of San Domenico Maggiore, Naples. In 2006, an autopsy was performed revealing a large pelvic mass and the molecular analysis was consistent with a primary bowel cancer. Three-quarters of colorectal cancers are adenocarcinomas arising via an accumulation of genetic changes from benign adenomatous polyps (see Figure 2.8). Adenomas are usually slow growing and the risk of malignant transformation increases with their size and how long they have been present.

Presentation

Diagnosis

In outpatients, the surgeon should take a full history from the patient and examine him or her. This should include a rectal examination, which may show the patient to have melaena. Proctoscopy and sigmoidoscopy should be performed in the outpatient setting. Blood tests should be organized, which should include a full blood count, renal function and liver function tests. A chest X-ray should be carried out and a barium enema or colonoscopy arranged as an outpatient procedure. The barium enema may show narrowing of the colon. In malignancy, this narrowing is typical and has the appearance of an apple core (Figures 11.1 and 11.2). Endoscopy may show a stenosing lesion or a polyp. Biopsies should be taken of the suspicious area.

Staging and grading

The tumour should be examined histologically. It is described as being either well, moderately or poorly differentiated. The original staging system for colorectal cancer was reported by Cuthbert Esquire Dukes, a British pathologist, in 1932. With various modifications this system is still in use today. Dukes’ stage reflects the degree of invasion of the tumour. Dukes’ stage A is specified when a tumour is confined to the mucosa. Dukes’ stage B is a tumour that perforates the serosa, and Dukes’ stage C is given when lymph nodes are affected. Tumours of the colon are, furthermore, divided according to their anatomical sub-sites. These are the appendix, caecum, ascending colon, hepaticflexure, transverse colon, splenic flexure, descending colon and sigmoid colon. Finally, the tumour can be staged according to the TNM clinical classification system (Table 11.3).

Treatment

The suspicion of malignancy having been raised, the patient should be worked up for surgery including an assessment of operability by CT scanning and by MRI. The CT scan will show whether or not there are enlarged lymph nodes within the abdomen and will define the possibility of further spread involving the liver. The MRI is more accurate than a CT scan in defining operability and in the staging of a rectal primary. If there is no gross evidence of dissemination, the patient with a colonic tumour should be admitted to hospital for colectomy. Removal of the primary is still considered in the presence of metastatic disease to reduce the risk of perforation or obstruction. However, the use of endoscopically placed stents has developed for those unfit for surgery or as a bridge to surgery in patients presenting with bowel obstruction (Figures 11.3 and 40.13).

The surgical plan depends upon the experience and practice of the clinician. There have been considerable developments in the area of laparoscopic surgery. If the patient is therefore considered to be an appropriate candidate, a laparoscopic colectomy might be performed. The results of rectal surgery are critically surgeon dependent, and much better results are obtained in centres where the surgeon specializes in this procedure.

Management of metastatic disease

Screening

As with other cancer screening programmes, the identification of high-risk groups for screening is important. Early colonoscopic screening studies focused on very high risk groups such as those with hereditary colon cancer syndromes and those with extensive inflammatory bowel disease. It is estimated that there may be a genetic predisposition to colorectal cancer in more than 20% of patients with these tumours. In the vast majority of colorectal cases there is, however, at present no direct evidence of there being a genetic risk. Patients with a risk of developing colorectal tumours can be stratified as having low, low–moderate, moderate, moderate–high or high risk of developing malignancy. The criteria for proceeding to screening for these patients are defined as in Table 11.4. Randomized controlled studies of whole population screening with FOB have shown that screening every 2 years those aged 45–74 reduces colorectal cancer mortality by 15–18%. Conversely, a screening one-off flexible sigmoidoscopy at the age of 55–64 reduces colorectal cancer incidence by 33% and mortality by 43%.

In 2006, the NHS bowel cancer screening programme introduced FOB tests for people aged 60–69 years every 2 years (Figure 11.4). It is estimated that if the uptake of FOB testing reaches 60% by the year 2026, 20,000 deaths from bowel cancer will be prevented in the United Kingdom. For every 1000 FOB tests completed, 20 (2%) will be abnormal and 16 (1.6%) patients will proceed to a colonoscopy, 6 (0.6%) of these will have polyps, 2 (0.2%) will have cancer and 8 (0.8%) a normal colonoscopy. The cost estimate equation for FOB testing is £1000 for each life-year saved. FOB testing will miss tumours and lead to a number of false positive findings. Colonoscopy is a more accurate means of detecting cancers but requires full bowel preparation and sedation and carries a risk of perforation (around 1 in 1500). Although the costs of colonoscopy for screening normal populations is, unfortunately, not economic, it is the investigation of choice for high-risk populations (Table 11.4). Because of studies showing the benefits and safety of one-off sigmoidoscopy, NHS England is planning to supplement FOB screening with flexible sigmoidoscopy screening of the population at 55 years of age.

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