19 September 2018

How common is serrated polyposis syndrome?

Clinical Gastro

Serrated polyposis syndrome was defined with arbitrary criteria by Burt and Jass in 2000.1 Epidemiological studies from the same time reported an incidence as low as one in 3000 on screening sigmoidoscopy.2, 3

More recent data suggested that the condition is more prevalent than previously thought, with rates of 0.3%, 0.4% and 0.8% reported in Italian4, Spanish and Dutch cohorts respectively5. 

This change in epidemiology likely reflects a change in detection rate. This increased detection could relate to multiple factors, including improved endoscopy equipment, split bowel preparation and improved endoscopist awareness of sessile serrated adenoma endoscopic appearances and morphology. 

It is now apparent that serrated polyposis syndrome is not a “rare syndrome”, however the exact prevalence remains unknown6 and there appears to be a significant geographic variability.5 Risk factors for the development of these lesions are also largely unknown. 

Australian authors have led the world in both describing the biology and pathology of sessile serrated lesions and articulating the potential risk that these lesions present endoscopically.7-10

In 2018, we will present data to the European Gastroenterology Meeting in Austria, from a regional Australian cohort showing that the rate of serrated polyposis syndrome  is in the order of one in 33 patients who present for colonoscopy for any cause. 

This is by far the highest rate ever reported. We identified an older mean age in both men and women, but in women there appears to be two peaks with a cohort of young women identified in their 30s.

So, what is it that proves risky about these lesions, what should general practitioners know about this syndrome, and how does it fit in with bowel cancer screening?

Firstly, these lesions are flat, sometimes very flat, they resemble the surrounding mucosa and require a high degree of vigilance on the part of the endoscopist and adequate training to identify tell-tale “shadows” that may indicate their presence (such as a mucus cap). 

The endoscopist then needs to be careful to identify the full extent of the lesion to avoid partially resecting these lesions, leaving adenoma in place. 

The next step is co-ordination with the histopathologist. The histopathology resembles a hyperplastic polyp and requires a careful microscopic examination to appropriately identify their tell-tale features. 

Communication between the endoscopist and histopathologist can see a change in the “risk profile” of these lesions.11 The possible predilection for the right colon has led some authors to hypothesise that these lesions may be partly responsible for the lower “protection” of the right colon for colorectal carcinoma post colonoscopy than the left colon.12

All of this information needs to be collated along with the family history, which has bearing in the diagnosis of this syndrome.

Currently the criteria for this syndrome requires that a patient present with a specific number and/or size and location of these polyps or have a family member with the syndrome and have just one of these sessile serrated lesions (polyp).

GPs should be aware that this syndrome increases the risk of bowel cancer and requires regular surveillance colonoscopy. 

The GP should also be aware of some of the non-invasive test performance characteristics that can lead to this being missed. 

Faecal occult blood testing in all its current forms uses an immunochemistry test for intact human haemoglobin. This requires a small amount of blood to be lost from the lesion or polyp.

For many years it has been known that this test performs better with more advanced lesions (higher sensitivity). It would appear that sessile serrated lesions tend not to leak blood as often until they are advanced lesions.13 This impairs the ability of non-invasive tests to detect these lesions, identify at risk individuals and therefore enrol these patients in appropriate surveillance programs.

It would also appear that not all sessile serrated lesions are equal.

For many years it has been known that the faecal occult blood testing performs better with more advanced lesions

The natural history of many of these lesions is indolent. However, once a lesion develops dysplasia the time to cancer is accelerated, possibly in the order of just a couple of years.

Australian researchers have shown that this pathway is not a common cause of bowel cancer in young people, however it is unknown whether these lesions are a risk factor for other lesions.8

When I moved to Port Macquarie, New South Wales, in 2013, I noticed that some patients who had previously had colonoscopies had multiple sessile serrated lesions at surveillance colonoscopy. It seemed that these lesions and people with multiple lesions were more common than expected. 

I had introduced split bowel preparation and hypothesised that improved cleaning of the right colon may have improved the detection of these lesions.

In late 2014, new endoscopes were purchased and detection of these lesions again increased. We therefore examined data from all the patients undergoing colonoscopy in my practice between January 2015 and March 2018. Patients found to have serrated polyposis syndrome, as defined by the WHO revised criteria, were included.

We found that in the study period, 3725 separate patients underwent colonoscopy and that serrated polyposis syndrome was identified in 110 of these (2.95%). This group was predominately female (68/110; 62%) and had an average age of 66.3 years (SD = 13.1; range 24-88 years). 22% of patients had a smoking history (5% current smokers; 16% former smokers), 9% of patients were diabetic and 20% consumed two or more standard drinks of alcohol per day.  Nearl half (47%) of patients had a family history of bowel cancer (32% in a first degree relative and 15% a second degree relative) and 15% of patients underwent colonoscopy for the evaluation of a positive FOBT. 

Most of the patients (107/110, 97%) were diagnosed with serrated polyposis syndrome based on the WHO criteria of having five or more polyps proximal to the splenic flexure with at least two greater than 10mm. 

Three (3%) patients had a first-degree relative with the syndrome and at least one serrated lesion. The median number of lesions detected during colonoscopy was 8 (range: 5-30) and then mean size of the largest lesion was 18mm (SD = 5.4mm). Dysplasia was detected within a serrated polyp in 30% of patients. In a majority of patients, other polyp types were also detected during colonoscopy (83%) with conventional tubular adenomas (33%) and hyperplastic polyps (7%) being the most common (42% had multiple other polyp types).  

We also noted that there was a bimodal distribution of female patients with a peak in the early years. While this may represent a selection bias, it warrants further study.

This data raises questions about the true prevalence of this condition in Australia. We have no data to suggest that patients on the mid-north coast (many of whom have lived most of their lives in larger cities and retire here) represent a different (biased) sample (though more research is needed). 

Is this rate due to a detection bias? 

This is certainly our leading hypothesis based on improved bowel preparation, equipment and training. 

If this is a more common condition than previously thought, it may have implications on screening due to the relatively poor performance of FOBT in detecting these lesions. 

It is possible that a new paradigm might emerge when thinking about how to screen for sessile serrated lesions. The question becomes, how to best screen for sessile serrated lesions or serrated polyposis syndrome? 

It may come to pass that in future iterations of bowel cancer screening guidelines, Australians may follow the path of American societies and recommend either optical or non-invasive investigations as first-line screening for average risk individuals rather than non-invasive only. 

There are significant issues to consider when arguing for colonoscopic screening. 

Firstly, as GPs and patients know, this procedure has a small but real risk of harm. Secondly there is a cost to the health system for these procedures and a positive test (detection of sessile serrated lesions) may mean that a patient is left with a significant screening burden (especially during childbearing years), which carries more risk. 

Ideally, we will develop a “Goldilocks” guide for our patients where screening is performed using the most appropriate tool, not too often to increase the risks associated with colonoscopy, but not too infrequently to increase the risk of interval colorectal carcinoma. 

There appears to be a global trend to earlier screening for colorectal carcinoma. 

As we learn more about the epidemiology of serrated polyposis syndrome  and sessile serrated lesions, guidelines may develop to tailor our approach to detection of these lesions and this syndrome.

Dr Stuart Kostalas is a gastroenterologist in Port Macquarie, NSW. He has a Masters in Medicine (Clinical Epidemiology) and is currently completing further postgraduate study (MSc) in the Centre for Evidence-Based Medicine at the University of Oxford. His clinical interests are advanced mucosal resection, including endoscopic submucosal dissection of neoplastic tissue in the GI tract and the detection of sessile serrated lesions.

References:

1. Snover DC, Ahnen DJ, Burt RW, Odze RD. Serrated polyps of the colon and rectum and serrated (“hyperplastic”) polyposis. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer; 2010.

2. Lockett MJ, Atkin WS. Hyperplastic polyposis (HPP): prevalence and cancer risk. Gastroenterology. 2001;120(5):A742.

3. van Herwaarden YJ, Verstegen MH, Dura P, Kievit W, Drenth JP, Dekker E, et al. Low prevalence of serrated polyposis syndrome in screening populations: a systematic review. Endoscopy. 2015;47(11):1043-9.

4. Colussi D, Zagari RM, Morini B, Fabbri M, Montale A, Hassan C, et al. Prevalence of serrated polyposis syndrome in an FIT-based colorectal cancer screening cohort in Italy. Gut. 2016.

5. IJspeert JEG, Bevan R, Senore C, Kaminski MF, Kuipers EJ, Mroz A, et al. Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview. Gut. 2017;66(7):1225-32.

6. Sweetser S, Smyrk TC, Sinicrope FA. Serrated colon polyps as precursors to colorectal cancer. Clinical Gastroenterology and Hepatology. 2013;11(7):760-7.

7. Burgess NG, Tutticci NJ, Pellise M, Bourke MJ. Sessile serrated adenomas/polyps with cytologic dysplasia: a triple threat for interval cancer. Gastrointestinal endoscopy. 2014;80(2):307-10.

8.  Liu C, Bettington ML, Walker NI, Dwine J, Hartel GF, Leggett BA, et al. CpG Island Methylation in Sessile Serrated Adenomas Increases with Age, Indicating Lower Risk of Malignancy in Young Patients. Gastroenterology. 2018.

9. Bettington M, Walker N, Rosty C, Brown I, Clouston A, Wockner L, et al. Critical appraisal of the diagnosis of the sessile serrated adenoma. The American journal of surgical pathology. 2014;38(2):158-66.

10.  Fernando WC, Miranda MS, Worthley DL, Togashi K, Watters DJ, Leggett BA, et al. The CIMP Phenotype in BRAF Mutant Serrated Polyps from a Prospective Colonoscopy Patient Cohort. Gastroenterology research and practice. 2014;2014:374926.

11. Tate DJ, Jayanna M, Awadie H, Desomer L, Lee R, Heitman SJ, et al. A standardized imaging protocol for the endoscopic prediction of dysplasia within sessile serrated polyps (with video). Gastrointest Endosc. 2018;87(1):222-31.e2.

12. Hermann Brenner, Michael Hoffmeister, Volker Arndt, Christa Stegmaier, Lutz Altenhofen, Ulrike Haug; Protection From Right- and Left-Sided Colorectal Neoplasms After Colonoscopy: Population-Based Study, JNCI: Journal of the National Cancer Institute, Volume 102, Issue 2, 20 January 2010, Pages 89–95.

13.  Hirai HW, Tsoi KK, Chan JY, et al. Systematic review with meta-analysis: faecal occult blood tests show lower colorectal cancer detection rates in the proximal colon in colonoscopy-verified diagnostic studies. Aliment Pharmacol Ther. 2016 Apr;43(7):755-64.