Iron Deficiency Anaemia And Bowel Cancer Biology Essay

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Ireland has the highest mortality rate for bowel cancer in Western Europe, with over 900 people dying from the disease each year. Over the past 15 years, the incidence of bowel cancer has increased by 20 percent. (Cancer society of Ireland)

In order to reduce the incidence and mortality of bowel cancer it is imperative that high risk patients and patients with symptoms/signs of colorectal cancer are screened adequately.

Colonoscopy is currently the gold standard for screening, diagnosis and monitoring of colorectal cancer as well as inflammatory bowel disease. Colonoscopy has the ability not only to inspect but also obtain tissue samples and remove polyps from the bowel. It use has led to an extensive expansion of knowledge of the natural history of colonic neoplasia. (Jerome D. Waye 2009)

Colonoscopy is an expensive and time consuming resource which is in high demand. It is an invasive procedure which carries with it the risk of perforation, bleeding and the need for intravenous sedation. (Clements, Tawfiq et al. 2009)Therefore, it is essential that patients referred for the procedure are done so appropriately to ensure that those most at risk are investigated the best use of limited resources and a high diagnostic yield for the procedure.

Extensive research has been carried in order to identify which colonic symptoms are most likely to correlate with an underlying carcinoma or adenoma, as well as to identify those patients who are at a higher risk then the general population of developing colorectal cancer. This should act as the basis for screening asymptomatic individuals or referring them for diagnostic colonoscopy. This literature review aims to summarise and evaluate the evidence for correlation of clinical symptoms with colonoscopy findings as well as the recommendations for colonoscopy, given by the various publications.

Search Strategies

An electronic search was performed using Pub Med. Combinations of MeSH terms and text words were used. These included "colonoscopy" "indications"" guidelines" "anaemia" " iron deficientanaemia""diarrhea""constipation""rectal/gastrointestinal""bleeding/haemorrhage" "screening/surveillance" and "colorectal cancer/neoplasm/".Bibliographies, references and clinical guidelines were also searched.

The titles and abstracts of all pertinent articles were reviewed and cross referenced. Articles were critically appraised, taking into account the impact factor of the journal, sample size and statistical analysis.

Results:

Five studies were found that aimed to identify the risk of colorectal cancer posed by particular symptoms.

Hamilton et al performed a large a case-control study which involved 21 General practices in the UK. 359 patients with colorectal cancer and 1744 controls, matched by age, sex and general practice were studied. This study concluded that there are ten features associated with cancer of the colon/rectum prior to diagnosis. These were identified as rectal bleeding, weight loss, abdominal pain, diarrhoea, constipation, abnormal rectal examination, abdominal tenderness, positive FOB and blood glucose less than 10 mmol/l. The positive predictive values for these symptoms and the 95% confidence interval were as follows: rectal bleeding 2.4% (1.9, 3.2); weight loss 1.2% (0.91, 1.6); abdominal pain 1.1% (0.86, 1.3); diarrhoea 0.94% (0.73, 1.1); constipation 0.42% (0.34, 0.52); abnormal rectal examination 4.0% (2.4, 7.4); abdominal tenderness 1.1% (0.77, 1.5); haemoglobin <10.0gdl−1 2.3% (1.6, 3.1); positive faecal occult bloods 7.1% (5.1, 10); blood glucose>10mmol/l 0.78% (0.51, 1.1): The results for all symptoms were statistically significant that is all P<0.001. It is evident from this study that bleeding symptoms, iron deficient anaemia and abnormal rectal examination have highest positive predictive values whereas non bleeding symptoms such as constipation, diarrhoea and abdominal pain were identified as features that have much lower positive predictive values for colorectal cancer. (W Hamilton 2005).

Many other studies have voiced similar opinions to Hamilton et al, an earlier study by Rex et al which reviewed colonoscopy indications and their yield for cancers found that bleeding symptoms and iron deficient anaemia had a substantial yield for cancers.(Rex 1995)This opinion was again voiced by a later study published in the Oxford journal of Medicine which found that 4% of patients referred for investigation of unexplained IDA were diagnosed with a colorectal malignancy. (M.R Stephens 2006)

A systemic review published by cancer research UK which looked at eight studies and 2323 patients however, differed in opinion. They found that in patients with rectal bleeding or Iron deficient anaemia, no additional "symptom, sign or diagnostic test is able to shift the probability of colorectal cancer to the extent of" ruling in" or "ruling out" the diagnosis of colorectal cancer with any degree of certainty. This is supported by the evidence that even red flag symptoms such as weight loss and bloody diarrhoea, have only a modest-diagnostic value.(Olde Bekkink, McCowan et al. 2010) Pepin and Ladabaum et al found that while in patients with symptoms such as constipation the yield of cancers on investigation by colonoscopy is similar to that of asymptomatic patients undergoing screening colonoscopy.(Pepin and Ladabaum 2002)

A number of papers have been published by the American society of Gastroenterologists(ASGE),British Society of Gastroenterologists as well as the National Institute of excellence(NICE) and other experts in the field of Gastroenterology to recommend when it is necessary to refer patients with colonic symptoms, both bleeding and non bleeding, for investigation.

Bleeding:

With regard to rectal bleeding, only two large bodies the ASGE and NICE have published guidelines. These published guidelines however differ substantially. The ASGE recommend that all patients with a positive faecal occult blood test should undergo a colonoscopy.(Davila, Rajan et al. 2005) While NICE guidelines recommend that only those over the age of 60 should be considered for colonoscopy if rectal bleeding is the only indication and in addition it must be present for at least six weeks. Meanwhile it recommends that in those aged between forty and sixty, only those patients who have rectal bleeding and a change in bowel habit towards looser stools for 6 weeks or more should be considered for routine referral for colonoscopy. Given that the previous research has found that diarrhoea has a much lower positive predictive value than rectal bleeding(W Hamilton 2005) and that besides rectal bleeding no other symptom can rule in or rule out colorectal cancer(Olde Bekkink, McCowan et al. 2010) ,the guidance given by NICE is very surprising and may require updating. Although one could argue that????? (REMEMBER NICE IS BASED ON COST ASWELL AND RESOURCE UTILISATION).

However, in patients with outlet rectal bleeding which is defined as the presence of bright red blood after or during defecation who have no other significant indications for colonoscopy such as a strong family history of colorectal cancer, flexible sigmoidosopy is sufficient to exclude significant pathology.(Marderstein and Church 2008)This is also the opinion of the ASGE however, they limit it further to include only those below the age of 40.Research published however has shown that in patients 40 years or younger presenting with rectal bleeding 8.9% were identified as having adenomatous polyps. This may suggest that in those under 40 investigation by colonoscopy may be justified and should be recommended in order to help prevent further advancement to adenocarcinoma.(Acosta, Fournier et al. 1994)

Iron deficiency anaemia:

Iron deficiency anaemia has a prevalence of 2-5% among adult men and post menopausal women in the developed world .(A F Goddard 2000). It has been found that bleeding from the gastrointestinal tract is the most common cause of Iron deficiency anaemia in both adult men and post menopausal women(A F Goddard 2000) and often it is the only clue to the diagnosis of colorectal cancer. It has also been identified as one of the only reliable predictors of colorectal cancer in a patient(Olde Bekkink, McCowan et al. 2010)and therefore it is a symptom that should be considered seriously.

Currently, the BSG and Nice both recommend that an urgent referral for upper and lower GI investigations be considered in men of any age with unexplained IDA and a Hb of 11g/100 ml or below. Also in non menstruating women with unexplained IDA and a HB of 10g/100 ml or less again a referral in highly recommended. Colonoscopy however is not recommended for pre-menopausal women unless there is a history of other colonic symptoms, or a strong family history of colorectal cancer. This is defined as a first degree relative less than 45 years of age or 2 affected first degree relatives, or if the iron deficient anaemia is persistent.(A F Goddard 2000)

Although, no order of investigations is specified by the BSG, a retrospective study by M.R Stephens et al. which reviewed the results of 3798 investigations in 2600 patients has found that "potentially curable gastrointestinal malignancy was diagnosed over 13 times more commonly using colonoscopy or barium enema vs. OGD ". Therefore, it would be favourable to investigate the lower GI tract first or alternatively perform both investigations together. (M.R Stephens 2006)

Diarrhoea:

Most cases of diarrhoea are caused by an acute self limiting infection. They are extremely common and generally supportive therapy is all that is required. As these infections are short lived, acute diarrhoea is not an indication for colonoscopy. However, if it is chronic-described as 3 weeks by ASGE or 6 weeks by NICE, endoscopy investigation is required. Initial investigation can be with flexible sigmoidoscopy, however if it is non diagnostic or symptoms persist colonoscopy should be performed.(Shen, Khan et al. 2010)No randomised controlled studies have yet been performed to evaluate one endoscopic procedure over the other and therefore, it is recommended that clinical decisions be individualised to each patient.

Constipation:

This is a very common symptom and is thought to affect approximately 20% of the Irish population .However, NICE have published no recommendations with regard to this symptom and the detection of colorectal cancer. Studies in this regard have been conflicting. Some have shown that the yield of colonoscopies for constipation alone is low and is comparable to with asymptomatic patients undergoing investigation.(Pepin and Ladabaum 2002). Others, however, have shown that chronic constipation is associated with an increased risk of cancer.(Qureshi, Adler et al. 2005) Thus, the ASGE recommends that those over the age of 50 with chronic constipation and no previous colon cancer screening should be referred. Those in the younger age group should have a flexible sigmoidoscopy.

Of importance, constipation associated with another lower GI symptom has a statistically significant increased risk of significant finding on investigation by colonoscopy(Gupta, Holub et al. 2010).Therefore, ASGE recommends that those with other symptoms such as rectal bleeding, positive FOB, weight loss and iron deficient anaemia should be referred for colonoscopy

Non specific symptoms:

Those with non specific abdominal symptoms do not have any more of a risk of serious colonic pathology than asymptomatic patients referred for colonoscopy.(Liebermann DA 2000).NICE recommends that in patients with equivocal symptoms, non-invasive investigations such as a full blood count may help in identifying the possibility of colorectal cancer.

Conclusion:

There remains a lack of clinical studies assessing the question of outcomes of colonoscopy based on clinical indication amongst the Irish population. Therefore there is a clear need for further studies in the area. Also to date, no guidelines have been published by the Irish society of Gastroenterologists to provide guidance for physicians in Ireland as to when referral for colonoscopy is required. The last set of guidelines for referral for colonoscopy were published by ASGE in 2000 and NICE in 2005.As these are somewhat outdated, for now Irish physicians must rely on clinical expertise and recently published literature to determine which patients to refer for this much sought after investigation.

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