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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