Objective of the audit
The objective of this audit is to measure current practice in prostate cancer against the recommendations in the guideline. The audit criteria and data collection tool are intended to be used as part of a local audit project, by either using the whole tool or cutting and pasting the relevant parts into a local audit template.

Audit criteria and standards
This document provides audit criteria based on the guideline’s key priorities for implementation for use in clinical audit. Users can cut and paste these criteria into their own programmes. The standards given are typically 100% or 0%. If these are not achievable in the short term, a more appropriate standard should be set based on discussions with local clinicians. However, the standards given remain the ultimate objective.

Data collection tool
A tool is provided that can be used or adapted by the Trust, service or practice for the data collection part of the clinical audit cycle. Exception codes are included where relevant and the tool indicates where a ‘not applicable’ (NA) answer is appropriate and where no exceptions or NA codes is acceptable. Suggestions on where you might find relevant information are included, although this may be different in your organisation.

Patient groups and sample
The audit should include adults with a biopsy-proven diagnosis of primary adenocarcinoma of the prostate or an agreed clinical diagnosis when biopsy would be inappropriate (agreed clinical diagnosis could include digital rectal examination, high PSA and known metastases). An appropriate sample should be selected in line with your local clinical audit strategy.

Data sources
The audit criteria may require data to be collected from a range of sources, including policy documents and patient records. Suggestions are indicated on the tools.

Re-audit
Whether or not the audit findings meet the standard, re-auditing is a key part of the audit cycle. If the first data collection and analysis shows room for improvement, an action plan should be developed and the audit should be re-run once changes to the service have had time to make an impact. Depending on the nature of the changes, this could take weeks or months. This process should be continued until the results of the audit meet the standards.

Links with other national priorities
The guideline development group considered that the evidence base was insufficient to place cryotherapy in the pathway of care for patients for the treatment of prostate cancer. They recommended that further research is required.

NICE has been in discussion with Industry, the British Association of Urological Surgeons (BAUS) and the Health Technology Assessment programme of the National Institute for Health Research to identify a way forward.

It is anticipated that a national data collection will be established and surgeons wishing to undertake this procedure will be expected to contribute to the evidence base. The design and nature of this national study will be discussed further at the next BAUS national meeting.
At the present time if surgeons are collecting local data that will be available for national analysis this should be considered in accordance with the NICE guidance.

The guideline development group considered that the evidence base was insufficient to place High Intensity Focused Ultrasound (HIFU) in the pathway of care for the treatment of prostate cancer. They recommended that further research is undertaken.
There is a current trial assessing the treatment of areas of prostate cancer within the prostrate gland (focal ablation) funded by Cancer Research UK – http://www.cancerhelp.org.uk/default.asp

NICE has been in discussion with Industry and has been informed that Disease Registries are being established in the UK. If surgeons are recruiting patients into a trial or collecting registry data that will be available for comparative assessment then this should be considered in accordance with the NICE guidance.

Further guidance
Click here for further guidance and generic templates to support the reporting and monitoring of the audit of NICE guidance in your organisation.

Epidemiology:
Highly prevalent in the population, especially among older population (up to 50% over 60s have an adenomatous polyp).
More likely to develop polyps if:
Over 50’s
If there is a family history of polyps
If there is a personal history of polyps
If there is a family history of colon cancer

Other factors:
Smoker
Drinker
Overweight
Excessive fatty food intake?
Differences in dietary fibre and antioxidants?
Protection by calcium and folate?

Presentation:
Most polyps are asymptomatic until they grow to 2cm in diameter
They can lead to bleeding, frank blood or microscopic bleeding (presenting with anaemia)
Polyps rarely present with a change in bowel habit – but large polyps in the rectum can present with tenesmus.
A large amount of mucus can also be passed.
Rarely a polyp will prolapse through the anus or act as an apex for an intussception.

Classification of polyps:

Adenomatous polyps:
Tendency to lead to colorectal cancer.
The early stages of malignancy, including dysplasia and carcinoma in situ may be found.
Carcinogens which produce adenomas experimentally also lead to cancer formation.
The size of the polyp appears to be a factor in determining the likelihood of the polyp becoming malignant. Rare for malignancy to occur with a polyp <1cm, and likelihood increases with size
Adenomatous polyps can be subdivided into the better differentiated tubular adenomas (75%) – often on a stalk and less differentiated villous adenomas (10%) – often sessile. An adenomatous polyp with a morphology in between these is called tubulovillous (15%).
Tubulovillous adenomas are more commonly found in the rectal area. The degree of villous component has been found to be correlated to the premalignant risk
Villous adenomas are larger, and are more likely to be non pedunculated. They are associated with the highest morbidity and mortality rates of all polyps. They can cause hypersecretory syndromes characterized by hypokalemia and profuse mucous discharge and can harbour carcinoma in situ or invasive carcinoma more frequently than other adenomas.
Adenomas can be sporadic or familial.

1.Familial multiple polyposis coli (FAP):
Arises from germline mutations of the APC gene located on chromosome 5q
It is inherited in an autosomal dominant fashion
Affects 1:10,000, men and women equally. 1 in 3 cases arise from new mutations with no previous family history, but subsequently leading to their children having a 50% chance of developing the disease.
Characterised by the presence of hundreds to thousands of neoplastic colorectal adenomas.
Mean age of development is 16 years, presenting with bleeding and diarrhoea.
Average age for developing colorectal cancer is 39 years. (Cancer development is almost inevitable by the age of 50). Aetiology factor of 1% of colorectal cancers.
FAP individuals also have a 10% risk of developing duodenal cancer – relatively rare in the general population.
Tracing and screening of relatives is essential (from 12years).
Affected individuals are offered prophylactic colectomy, often before the age of 20.
Surgical options include colectomy with ileorectal anastomosis, restorative proctocolectomy or pouch procedure.
Attenuated FAP can occur later in life (average age of 44 years) and can be missed. There are fewer polyps (<100) and tend to occur the right side of colon.
Gastric fundic gland polyps and duodenal adenomas are also frequently found.
Extraintestinal lesions are also found, including osteomas, epidermoid cysts and desmoid tumours. Congenital hypertrophy of the retinal pigment epithelium can occur with many FAP families.

2.Gardeners’ syndrome:
An autosomal dominant condition with multiple colonic adenomas and associated bony osteomas and epidermoid cysts.
Benign cysts can occur on the limbs, face or scalp, and benign bony tumours of the skull and lower jawbone can also occur.
A mutation of the same APC gene as FAP has subsequently been identified.

3.Hereditary non polyposis colon cancer (HNPCC):
Despite the name, does have associated colonic polyps, only fewer than FAP patients.
Accounts for 5-10% of colorectal cancers
Increased risk of other GI, urological, gynaecological cancers
Diagnosed by having 3 affected relatives, in 2 generations and one patient <50 years
Recommend to start screening with colonoscopy starting 5 years before youngest affected relative

Hamartomatous polyps:
A hamartoma is a lesion where there is an overgrowth of one or more of the cell types which are normal constituents of the organ from which they arise, and is defined as an abnormality of development.
They are commonly large and stalked.
With regards to colonic polyps, there are two types:

1.Juvenile polyps:
Occurs in children and teenagers (1-2 %)
May present with bleeding and intussception.
May spontaneously slough off and present with material passed with motions.
Histologically show mucus retention cysts.
They have a low malignant potential unless multiple polyps are seen
Can usually be treated colonoscopically
Juvenile polyposis is an autosomal dominant disease, and gene identified is SMAD4/DPC4. The inherited form has a 10% chance of developing into a malignancy in colon.

2.Peutz-Jeghers syndrome:
A rare autosomal dominant condition. Identified gene is LKB1.
Multiple hamartomatous polyps appear throughout entire GI tract, frequently in small bowel.
May bleed, cause small bowel obstruction or cause intussception.
There is also pigmentation of skin around lips and gums.
There is low malignant potential of the polyps, but overall the patient is at a greater risk of developing GI and non-GI carcinoma.
Treatment by individual polypectomy.
Follow up is every 2 years with x-ray and endoscopy.

3.Cowden syndrome:
An autosomal dominant disease
Intestinal polyps that are considered to be hamartomatous but with a mixture of cell types.
Skin stimata
Patients have an increased risk of various extraintestinal malignancies including thyroid, breast, uterine and ovarian.

Metaplastic polyps:
They are usually small, multiple and slightly raised above the surrounding normal mucosal.
Most frequently found (90% of all polyps)
Frequently found in rectum and sigmoid colon.
These pale sessile mucosal nodules usually measure <5cm. They do not have significant malignant potential. They cause no symptoms and their only relevance is to distinguish from adenomatous polyps. They are often seen in inflammatory bowel disease or lymphoid hyperplasia. Metaplastic polyposis (>10 colonic metaplastic polyps) is rare but appear to exhibit and increased risk of colon cancer.
If found incidentally (e.g. on appendicectomy) no further treatment is required.

Polyps due to protrusions of mesenchymal tissue:
Lipomas, leoimyomas, neurofibromas, haemangiomas can occur in the wall of the colon, if they form a lump which protrudes into lesion, by definition is a polyp.
They are relatively rare in clinical practise
Main importance is to distinguish from a carcinoma.

Inflammatory polyps:
Found in inflammatory conditions of the bowel such as pseudopolyps in ulcerative colitis or Crohn’s disease
They have no malignant potential.

Cronkhite-Canada syndrome:
An exceptionally rare condition
Involves multiple colon polyps with associated hyperpigmentation of skin and nail atrophy.
It affects middle aged and older patients
It is linked with malabsorption
Some response has been shown with vitamin E therapy.

Diagnostic tools:
1. Colonoscopy

May be able to differentiate between a metaplastic and a pre-malignant adenomatous polyp
Can also perform individual polypectomy.

2.Barium enema and X- ray
3.Sigmoidoscopy
4.PR – for rectal polyps only

Management:
1.  Polypectomy
Most are removed with colonoscopy
Using a wire snare which wraps around stalk of polyp and passing of electric current.
Painless
Safe, but can have risk of perforation (1 in 300) and bleeding (1 in 100)

2. Surgery
If polyp is >4cm and too big to be removed endoscopically
If there is an ill defined stalk and therefore endoscopic removal will have increased risk of bleeding
These polyps are more likely to be already cancerous in nature.
Large rectal polyps can be removed via anus.
Prophylactic colectomy offered for FAP patients

3. Follow up
Individual polyps that have been removed will not recur, but multiple new polyps can develop.
The National Polyp Study conducted in the USA showed that colonscopic polypectomy with surveillance reduced colorectal cancer incidence by 76-90%
Guidelines recommend a surveillance colonoscopy following polypectomy at: 3 years in patients with 1-3 polyps >1cm, 1 year for patients with more than 4 polyps, 5 years for small polyps <1 cm. If any doubt exists about the excision margins of any polyp then an earlier repeat examination is recommended. Genetic testing for gene mutations, especially for families of FAP patients. Prevention: So far, dietary factors have been inconclusive Certain cyclo-oxygenase inhibitors e.g. Sulindac have been shown to reduce the number of polyps that develop. This does not sufficiently reduce development to stop routine colonoscopies. Vitamin therapy under research Prognosis: 1.Metaplastic polyps: No significant premalignant potential, even if they are untreated. Rare metaplastic polyposis (>50) can increase colonic cancer risk

2. Adenomatous polyps:
Can all potentially become malignant, but actual risk per polyp is small.
Up to 50% of over 60 year olds have more than one adenomatous polyp, but only 6 % of people develop bowel cancer.
As long as the whole polyp is removed, there is no risk of recurrence or cancerous change of that polyp even when cancerous cells have invaded the stalk of the polyp.
Risk of recurrence is great however if original polyps were >1cm, or more than 4 polyps, or if dysplasia is shown.

3. Familial adenomatous polyposis
Likely when >100 adenomatous polyps are found
High risk of premalignancy
Colectomy recommended, including prophylactic colectomy following gene identification.

4. Juvenile polyps
Individual polyps have little pre-malignant potential
Familial juvenile polyposis carries a 10% risk of colon cancer and increased risk of gastric and duodenal cancers
In this case, yearly surveillance of occult blood in faeces and flexible sigmoidoscopy every 3-5 years

5. Peutz-Jeghers syndrome
Associated with an increased risk of cancer in small intestine and colon.
Colonoscopic surveillance recommended.

1. What if my report mentions “cecum”, “ascending colon”, “transverse colon”, “descending colon”, “sigmoid colon”, or “rectum”?

The cecum is the beginning of the colon where the small intestine empties into the large intestine. The ascending colon, transverse colon, descending colon, sigmoid colon, and rectum are, in order, other parts of the colon beyond the cecum. The colon ends at the rectum and waste exits through the anus.

2. What is adenocarcinoma of the colon?

Adenocarcinoma of the colon is the most common type of colon cancer (malignant tumor). Adenocarcinoma has a wide range of behavior from cases that are very slow growing with a low risk of causing harm, to cases that are more aggressive and can spread to other areas of your body.

3. What does “invasive” or “infiltrating” mean?

As colon cancer grows and spreads beyond the inner lining of the colon (mucosa), it is called “invasive adenocarcinoma”. It then has the potential to spread to other places in the body.

4. Does this mean that the tumor has invaded deeply and is associated with a poor prognosis?

Not necessarily. On a biopsy, the pathologist cannot typically determine the depth of tumor invasion. The depth of tumor invasion as well as prognosis are typically determined when the entire tumor is subsequently removed.

5. What does differentiation refer to?

Differentiation is the grade of the cancer and is determined by its microscopic appearance. It is an indication of the aggressiveness of the cancer. Colon cancer is usually divided into three grades (well differentiated, moderately differentiated, and poorly differentiated) or sometimes two grades (well-moderately differentiated and poorly differentiated).

6. What is the significance of the grade of colon cancer?

Grade is one of the many factors that helps determine the aggressiveness of a given cancer. Poorly differentiated colon cancers tend to be more aggressive than well and moderately differentiated colon cancers. However, other factors in addition to grade, such as how far the cancer has spread (which cannot be determined on the biopsy) also affect the prognosis.

7. What does it mean if there is vascular, lymphatic, or lymphovascular invasion?

These terms mean that cancer is present in the vessels (arteries, veins, and/or lymphatics) of the colon and that there is an increased chance that cancer could spread out of the colon. However, your cancer could still be very curable depending on other factors.

8. What is a polyp?

A polyp is a projection (growth) of tissue from the inner lining of the colon into the lumen (hollow center) of the colon. Different types of polyps have certain identifiable microscopic appearances. They are usually non-cancerous (benign) but, in some instances, cancer can arise in various types of polyps.

9. What does it mean if, in addition to cancer, my report says there are also other polyps such as adenomatous polyp (adenoma) or hyperplastic polyps?

Polyps are very common and in the setting of cancer elsewhere in the colon will typically not affect treatment and are nothing to worry about.

10. What is the significance if “mucin” or “colloid” is mentioned in my report?

Mucin is produced by the colon to help lubricate the colon. Colon cancers that produce large amounts of mucin are referred to as mucinous or colloid adenocarcinomas. However, on a biopsy specimen, the presence of “mucin” or “colloid” will not determine prognosis or treatment.

11. What does it mean if my biopsy report mentions special studies such as microsatellite instability and MSH2, MSH6, MLH1, and PMS2?

In some colon cancers, special laboratory testing may reveal an abnormality referred to as “microsatellite instability”’. Microsatellite instability is associated with several proteins including MSH2, MSH6, MLH1, and PMS2. Microsatellite instability may be due to a genetic defect that could be present in other family members. At times, additional tests may be necessary and your doctor can help determine when these are needed. Your doctor may use these test results to modify your treatment plan (type, or use, of chemotherapy) or to direct testing of other family members.

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Opr. DR. Muharrem Yılmaz