Inherited bowel cancer
Colonoscopy
How to Treat – Bowel cancer part 1: Diagnosis
Inherited bowel cancer
THE vast majority of patients who develop colorectal cancer in the setting of a positive family history do so through an ill-defined, heterogeneous mix of genes. There are, however, some specific syndromes for which testing is available. These syndromes have a profound impact on advice and testing for patients and their families.
Hereditary non-polyposis colon cancer Hereditary non-polyposis colon cancer( HNPCC) is an inherited autosomal-dominant defect of the DNA mismatch repair system. Normally, DNA replication errors are repaired during cell division. Patients who inherit one of the genes for HNPCC have defective mismatch repair and hence progressively accumulate DNA replication errors.
This predisposes them towards formation of specific malignancies, including colorectal cancer, cancers of the uterus and ovaries, cancers of the urinary system and small bowel cancer. Phenotypic expression of this genotype results in the formation of malignancies in 40-90 % of affected individuals.
In patients with HNPCC who develop bowel cancer, the lesions have specific features, which include a predisposition towards right-sided malignancies, an accelerated adenoma – carcinoma sequence and certain histological features.
Testing in patients with suspected HNPCC and those who develop bowel cancer can initially be performed using‘ pre-genetic tests’, including immunohistochemistry for expression of the usual mismatch repair gene protein products. This test is cheap, quick and can be performed on minimal volume tissue samples, including colonoscopic biopsies.
The most common reason for abnormal immunohistochemistry testing is acquired methylation, which can be tested for and effectively preclude a diagnosis of HNPCC. Not all patients with abnormal immunohistochemistry for mismatch repair gene protein products have HNPCC, but essentially all patients with HNPCC
Histological features of HNPCC-related bowel cancer
Right-sided cancer Mucinous or signet-cell component Medullary carcinoma B-cell lymphoid aggregates Intraepithelial T lymphocytes Microsatellite instability Poorly differentiated carcinomas
will demonstrate abnormalities on immunohistochemistry testing.
Polyp after injection of submucosal saline and methylene blue prior to polypectomy.
Amsterdam criteria for clinical diagnosis of HNPCC or Lynch syndrome 5 CRC diagnosed in a patient who is under 50
Presence of synchronous( at the same time) or metachronous( at another time, ie, a reoccurrence of) CRC or other Lynch syndrome – associated tumours, regardless of age
CRC with high microsatellite instability histology diagnosed in a patient under 60
CRC diagnosed in one or more first-degree relatives with a Lynch syndrome – associated tumour, with one of the cancers being diagnosed before the age of 50
CRC diagnosed in two or more first-degree or second-degree relatives with Lynch syndrome – associated tumours, regardless of age
Revised Bethesda criteria( 2004) to select those who need genetic analysis 6 CRC diagnosed in a patient who is under 50 Presence of synchronous or metachronous CRC or other Lynch syndrome – associated tumours, regardless of age CRC with high microsatellite instability histology diagnosed in a patient under 60
CRC diagnosed in one or more first-degree relatives with a Lynch syndrome – associated tumour, with one of the cancers being diagnosed before the age of 50
CRC diagnosed in two or more first-degree or second-degree relatives with Lynch syndrome – associated tumours, regardless of age
Familial adenomatous polyposis Like HNPCC, familial adenomatous polyposis( FAP) is an autosomal-dominant condition. The defect is located on chromosome 5, in the adenomatous polyposis coli gene, which usually suppresses the formation of polyps in the body. The loss of this gene causes hundreds, if not thousands, of polyps to develop throughout the colon, each with malignant potential.
Eventually, one or more of these polyps develops into a cancer( greater than 90 % risk by age 50). Polyps can also develop elsewhere, including in the gastric fundus and duodenum, and carry a similar risk of cancer. There is also an association with other malignancies, such as papillary thyroid cancer, pancreatic adenocarcinoma, desmoid tumours and osteomas.
Consider a diagnosis of FAP in families where there is a strong genetic predisposition towards colorectal cancer or other FAPtype cancers, or where more than 10 adenomas are found on colonoscopy. Definite diagnosis is confirmed by genetic testing.
Once the diagnosis is made, yearly screening with flexible sigmoidoscopy( from age 10-12) should commence. Patients in their 20s should receive counselling about possible prophylactic options: proctocolectomy with creation of an ileal pouch; proctocolectomy and end ileostomy; subtotal colectomy( with flexible sigmoidoscopic surveillance); or continued colonoscopic surveillance. Each of these options has their advantages and disadvantages.
The management of the colorectal cancer aspects of FAP has advanced to the point that patients usually die of other causes. These include the other FAP-associated tumours listed above, especially desmoid tumours. Therefore, with careful management, these patients can have a good prognosis despite their risk of malignancy.
Colonoscopy
IT is important to remember that colonoscopy is not simply a diagnostic modality, but unlike other screening investigations, has clear therapeutic potential. The majority of large bowel polyps can be removed using a colonoscope. A number of techniques and colonoscopic instruments can be used to remove polyps.
Small and favourable polyps If polyps are pedunculated, or small and sessile, they can usually be removed using either hot biopsy forceps or an endoscopic snare. This is generally performed at the time of diagnostic colonoscopy, unless there are specific contraindications. This is generally a safe and simple intervention, and does not require admission.
It is important to note that if patients are therapeutically anticoagulated, treated with antiplatelet therapy or have a coagulopathy, then it may not be possible or safe to proceed directly to polypectomy at the time of the scope. If patients have medical contraindication to polypectomy, they are generally not suitable for‘ direct access’ or open-access colonoscopy, and should see the colonoscopist in advance of booking.
Endoscopic mucosal resection For larger sessile polyps, conventional techniques of polypectomy have traditionally been associated with an increased risk of local cont’ d next page
Bowel cancer seen at colonoscopy.
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