First surveillance intervals following removal of large sessile or laterally spreading adenomas

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Definition

Large sessile and laterally spreading lesions (LSLs) are defined as those that are broadly attached to the mucosa. In general, the height of the lesion does not exceed 50% of the base and is usually much less. The Paris system is the accepted international standard for the classification of lesion morphology (see Figure 1, Colonoscopic surveillance after polypectomy – Introduction).[1][2] LSLs ≥10mm are subdivided based on their height above the mucosa as 0–11a (flat <2.5mm above the mucosa), 1s (sessile >2.5mm above the mucosa) or 0–11a + 1s (lesions with a combination of both morphologies). The uncommon 0–11b lesions (not elevated and completely flat) are also within this subgroup. The surface features of LSLs are further characterised as granular and non-granular. This has important implications for the risk of submucosal invasive disease (cancer), presence of submucosal fibrosis and ease of resection.[3][2][4]Back to top

Background

The 2011 Australian national clinical practice guidelines for surveillance colonoscopy[5] recommended follow-up colonoscopy at 3–6 months and again at 12 months following piecemeal removal of large and sessile adenomas to ensure complete removal.

Approximately 5% of colonic polyps encountered during colonoscopy are LSLs ≥10 mm. They may exhibit extensive growth along the bowel wall before developing an invasive component.[6] Large (≥20 mm) LSLs are considered high-risk precursors of colorectal cancer (CRCColorectal cancer). However, the majority are non-invasive and the absence of lymphatics in the colonic mucosa precludes lymph node metastasis enabling even very extensive LSLs to be completely resected and cured within a structured surveillance program, by endoscopic mucosal resection (EMREndoscopic mucosal resection).[7] All LSLs are candidates for definitive management by EMREndoscopic mucosal resection.

EMREndoscopic mucosal resection is an outpatient day procedure, which is proven as a safe and effective alternative to surgery for most LSLs. Prospective multicentre studies have defined the therapeutic capacities and limitations and highlighted the dramatic mortality and cost reduction when compared to surgery.[8][9] Excellent long-term outcomes have been demonstrated[10][11][12] including an approximately 4% risk of late recurrence at 18 months in individuals with EMREndoscopic mucosal resection scars that are clear at first colonoscopic surveillance at 4–6 months.

Adverse events have been reported. Post-EMREndoscopic mucosal resection bleeding occurs in 5–6% of patients. It is rarely life-threatening, but can be managed by supportive measures alone in two thirds with endoscopic intervention reserved for those with ongoing bleeding.[13] The main risk factor is right colon location with an odds ratio of 3–4 compared with those in the left colon.[14] Perforation occurs in 1–2%, but if it or its stigmata are recognised intra-procedurally by validated imaging criteria then endoscopic closure can be effected without sequelae.[15][16]

The major limitation of colonic EMREndoscopic mucosal resection is the high rate of adenoma recurrence of approximately 15–30% encountered at first surveillance colonoscopy.[7][11][12] This risk is closely related to the need for multi-piece excision. As size increases the possibility of single piece excision diminishes and it is rarely possible by EMREndoscopic mucosal resection for LSLs >20mm. Endoscopic submucosal dissection (ESDEndoscopic submucosal dissection) may achieve en-bloc resection, but is time-consuming, technically demanding, more expensive, mandates multiday hospital admission and in long term follow up offers no demonstrable clinical benefit over EMREndoscopic mucosal resection for the overwhelming majority.[17][18] Fortunately, EMREndoscopic mucosal resection recurrences are usually small, and easily treated at scheduled surveillance colonoscopy.[7][12] A structured surveillance protocol is a proven effective long-term strategy for eradication of recurrence.

Invisible, residual microscopic adenoma present at the resection margin may account for most recurrence encountered following EMREndoscopic mucosal resection. The Complete Adenoma Resection (CARE) study clearly demonstrated that, even for smaller lesions, incomplete resection with biopsy proven residual adenoma at the edges occurs frequently (10%) and that increasing lesion size correlates with higher incomplete resection rates of up to 23.3% for lesions 15–20mm.[19] Extra-wide field EMREndoscopic mucosal resection involves wider excision at the edges of the lesion including at least 5mm of normal-appearing tissue. This technique was not effective in reducing recurrence, most likely due to residual, endoscopically invisible microscopic adenoma at the lesion margin particularly in the areas between sequential snare placements.[20] Full publication of an Australian multicentre randomised controlled trial of complete thermal ablation of the entire EMREndoscopic mucosal resection defect margin is awaited.[21]

Risk factors for recurrence after EMREndoscopic mucosal resection include lesion size ≥40 mm, piecemeal resection and the presence of high-grade dysplasia (HGDHigh grade dysplasia) in the resected specimen.[7][11][22][23][24] Operator technique is also likely to be very important as can be inferred from the CARE study where there was a 4-fold difference in residual adenoma amongst endoscopists even though they knew their performance was being monitored.[19] Utilising a standardised imaging protocol incorporating narrow band imaging, even subtle recurrence is readily detected during follow-up.[25]

LSLs frequently have significant synchronous advanced pathology, including other LSLs, advanced adenomas, early cancers and serrated polyposis syndrome.[26] When an advanced lesion is found, a careful assessment of the entire mucosal surface of the colon is mandatory.

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Evidence

What is the appropriate colonoscopic surveillance after the removal of large sessile or laterally spreading adenomas? (SAD3)?

Systematic review evidence

The systematic review reported outcomes from 13 studies over 16 articles [10][7][24][27][28][29][30][31][32][33][34][35][36][37][38][39] examining surveillance colonoscopy for patients with large (≥20 mm) sessile and/or laterally spreading adenomas. There were seven prospective cohort studies and six retrospective cohort studies. Study types differed based on outcome.

For surveillance, there were 11 studies that were of aetiological type with all seven level II prospective studies and all six level III-2 retrospective studies, and level III-3 retrospective prognostic study. For cohort study outcomes, nine studies were at low risk of bias, no studies were at moderate risk of bias, and three studies were at high risk of bias.

For cohort study risk factor outcomes, only a single study had a low risk of bias, three studies had a moderate risk of bias, and the remaining nine studies were at high risk of bias.

Generalisability to the Australian population and healthcare environment varied between studies. Interpretation of the outcomes is genuinely uncertain due to a lack of consistency in the studies.

In summary, the systematic review did not demonstrate any additional information to guide decision-making. Accordingly the recommendations and practice points are based on consensus expert opinion.

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Evidence summary and recommendations

Evidence summary Level References
Three-month residual/recurrent adenoma incidence by patient varied between 9.86% and 30.13%, and residual/recurrent neoplasm incidence was 31.91%. By adenoma, 3 month residual/recurrent adenoma incidence was 22.22%. IncidenceAn epidemiological term reporting number of new cases in a population within a specified period. based on resection type was either not consistent or could not be determined, while patient numbers between studies varied in size. II, III-2 [27], [34], [40], [39], [29]
The incidence of residual/recurrent adenoma within 4–6 months varied between three studies reporting by patient with incidences of 4.92% and 28.00% for those undergoing piecemeal resection and 0.00% and 18.75% for those undergoing en bloc resection. All three studies had fewer than 100 patients. In one study that reported by adenoma, the incidence at 4–6 months was 11.11% for those that underwent piecemeal resection and 9.09% (n=342) for those that underwent en bloc resection (n=55). II, III-2 [36], [28], [33], [41]
For other studies with dissimilar surveillance times or that could not be compared, residual/recurrent adenoma incidences by patient were 25.00% at >6 months and 0.00% at ≥9 months. The incidence of residual/recurrent neoplasm was 23.53% at 15 months. By adenoma, incidences at 12 and 36 months were 11.11% and 0.00%. II, III-2 [28], [38], [42]
There was no significant difference between <12 and >12 months surveillance for residual/recurrent adenoma (by patient; p=0.266) nor when adenoma size was adjusted (OR=0.42, 95% CI=0.11–1.65, p=0.213).

Similarly, there was no evidence to suggest significant differences between en bloc and piecemeal resection for residual/recurrent adenoma, nor when adjusted for adenoma size (OR=1.70; 95% CI 0.46–6.27; p=0.423) as well as location, shape, histology and ablation used (OR=1.13; 95% CI 0.4–3.3; p=0.82).

This was also the case when EMREndoscopic mucosal resection and ESDEndoscopic submucosal dissection were compared (OR=2.14; 95% CI 0.18–24.74; p=0.544).

II, III-2, III-3 [31], [37], [29]
The risk between en bloc and piecemeal resection types was found to be almost 3.5 times greater for patients undergoing piecemeal (compared to en bloc) resection at minimum 4–6 months, which was statistically significant when adjusted (HR=3.4; 1.5-7.6; p=0.002). II [35]
Cumulative incidence of residual/recurrent adenoma was reported to be 16.1%, 20.4%, 23.4% and 28.4% at 6, 12, 18 and 24 months and for those with sessile serrated adenomas/polyps this was 6.3% at 6 months and 7.0% at 12, 18 and 24 months. The overall cumulative incidence of sessile serrated adenomas/polyps were found to be significantly lower than adenomas over time (p<0.001). II [35]
There were no studies that reported cancer incidence relating to the population of interest.
Consensus-based recommendationA recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.Question mark transparent.png

Large sessile and laterally spreading lesions

First surveillance interval should be approximately 12 months in individuals who have undergone en-bloc excision of large sessile and laterally spreading lesions.

Consensus-based recommendationA recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.Question mark transparent.png

Large sessile and laterally spreading lesions

First surveillance interval should be approximately 6 months in individuals who have undergone piecemeal excision of large sessile and laterally spreading lesions.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Consideration should be given to referring large sessile and laterally spreading lesions to experienced clinicians trained in and regularly undertaking high quality EMREndoscopic mucosal resection to reduce the risk of recurrence.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Patients with large sessile and laterally spreading lesions should be informed of the requirement for scheduled surveillance before proceeding to EMREndoscopic mucosal resection.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

At surveillance following piecemeal or en-bloc excision of large sessile and laterally spreading lesions, the EMREndoscopic mucosal resection scar should be identified, photodocumented and systematically evaluated for recurrence, including biopsies. These individuals are at high risk for synchronous and/or metachronous lesions and require very careful evaluation of the remaining colon at the same time.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Endoscopic mucosal resection (EMREndoscopic mucosal resection) of large sessile and laterally spreading lesions (>20mm) is usually piecemeal and all lesions that undergo piecemeal excision are at higher risk of recurrence and require scheduled surveillance. Risk factors for recurrence after EMREndoscopic mucosal resection are piecemeal excision, larger lesion size (>40mm) and the presence of high-grade dysplasia in the resected specimen.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

In patients who have undergone piecemeal excision of large sessile and laterally spreading lesions (in whom the first surveillance colonoscopy at 6 months is clear), the next surveillance colonoscopy should be considered around 12–18 months, especially in those who had large lesions (>40mm) or high-grade dysplasia at index EMREndoscopic mucosal resection.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Consideration should be given to tattooing all lesions which may need to be identified subsequently. Those that may need surgical resection should be tattooed distal to the lesion in three locations around the circumference of the bowel to facilitate recognition.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Consistently high-quality colonoscopy is imperative for optimal cost effectiveness and for implementation of uniform surveillance guidelines.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

PolypA small growth protruding from a mucous membrane, such as the lining of the bowel./adenoma size as per the endoscopist documentation should be used for determining surveillance intervals. All endoscopists should ensure size measurements are accurate using a reference standard (eg an open biopsy forceps or snare).

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Notes on the recommendations

High-quality scientific evidence to determine the optimal surveillance interval following removal of large sessile and LSLs is limited. There are no randomised controlled trials comparing one surveillance interval with another.

There is no high-quality evidence to guide the timing of second surveillance colonoscopy. Back to top

Health system implications

Clinical practice

Implementation of these recommendations would not significantly affect current practice.

Resourcing

Implementation of these recommendations would not require additional resources.

Barriers to implementation

No barriers to the implementation of these recommendations are envisaged.

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References

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Appendices

Jutta's magnifying glass icon.pngPICO question SAD 3 View Evidence statement form SAD3Evidence statement form SAD3 View Systematic review report SAD3Systematic review report SAD3
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