Endoscopic resection in the colon: A practical guide. Michael Bourke

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1 Endoscopic resection in the colon: A practical guide. Michael Bourke INTRODUCTION Colonoscopic polypectomy is a fundamental tool in the prevention and treatment of colorectal cancer. Colonoscopic polypectomy reduces the anticipated incidence of colorectal malignancy in patients with significant adenomas by approximately 80% in longterm follow up 1-3. Between 80-90% of adenomatous lesions are 10 mms size and conventional snare polypectomy has been the accepted treatment for more than 3 decades. Such lesions do not pose a significant challenge to an appropriately trained and skilled colonoscopist 4. However, the assessment and treatment of larger lesions greater than 20 mms in maximum dimension is an evolving field of knowledge. LESION ASSESSMENT AND INDICATIONS: EMR is indicated for sessile colonic lesions >10mm in maximum dimension that are being considered for endoscopic treatment. Smaller or pedunculated lesions can generally be safely removed with a conventional snare technique. All sessile lesions should be carefully characterised and assessed for the risk of submucosal invasion (SMI) before excision. If a significant risk for SMI exists, then this may suggest a change in the endoscopic treatment strategy or the need for surgery. En-bloc resection is preferable if the risk for SMI is substantial. INSTRUMENTS AND EQUIPMENT: Snares Snare selection is to some extent an individual choice, but stiff type snares have clear advantages for tissue capture. We prefer a snare with a serrated wire to facilitate entrapment of normal tissue at the margin of the lesion. A range of sizes and configurations is required including oval, round and hexagonal from 10 to 20 mms for flat lesions. For large pedunculated and bulky exophytic lesions, large snares of 3 x 4-6 cms, oval or hexagonal, are necessary. The 20 mm spiral snare is our standard instrument for large en bloc (15-20 mms and above) and extensive piecemeal ER. The diameter of the wire is 0.48 mm. Small residuals at the margins are excised using a thin wire mini oval snare. The smaller wire diameter of 0.3 mm facilitates better tissue capture in this case. Electrosurgery Microprocessor-controlled electrosurgical generators capable of delivering alternating cycles of high frequency short pulse cutting with more prolonged coagulation current are required. [Erbe VIO 300 (Tübingen, Germany); Olympus ESG-100 (Tokyo, Japan)]. These generators sense tissue impedance via

2 signals from the return electrode and adjust power output accordingly. In the authors view, generators without these features do not provide an acceptable level of electrosurgical safety for extensive and complex EMR. Unintentional deep tissue injury may occur leading to serositis and the potential for delayed perforation. Injection solution The ideal solution should be inexpensive, readily available, non toxic, easy to prepare and inject and provide a long lasting submucosal cushion 22. Ideally it should also provide a well circumscribed rather than diffuse elevation and thus a substantial difference in elevation between the target lesion and the uninvolved non-neoplastic surrounding tissue 23. This greatly facilitates the technical ease of resection. Although normal saline is most commonly used there are a wide variety of alternatives, each with their own limitations, reflecting the absence of a clearly superior solution. Normal saline s advantages include ease of use, isotonicity, non-allergenicity and lack of toxicity if injected transmurally. However the submucosal cushion is relatively short lived and the mucosal elevation is not as marked as other solutions. It is also limited by its dispersion within the submucosal plane and thus tissue elevation is not well circumscribed. Numerous alternatives including hyaluronic acid, hydroxypropylmethyl cellulose, glycerol, fibrinogen, hypertonic saline, dextrose and/or autologous blood are limited by expense, complex preparatory requirements, localised tissue inflammation and damage and administration difficulties 22,24. Succinylated gelatin (SG) is a widely available inexpensive, safe colloidal solution that is commonly used for intravenous fluid resuscitation. It exerts an oncotic pressure comparable to that of human albumin. A biologically inert blue dye such as indigo carmine in a concentration of 0.04% (equating to 1 ml from the standard 4 mg/l solution) is used in the injection solution. The benefits are threefold 26 : The dye defines the perimeter of the lesion. This is especially beneficial in subtle pathology where the neoplasm may merge imperceptibly with the surrounding mucosa, for example 0-IIb non granular lesions or sessile serrated adenomas. This eliminates the need for pre-resection thermal marking of the margins of the target which is usually not necessary in the colon. The blue coloration delineates the extent of the submucosal cushion, thus defining the safe EMR zone. Dyes such as indigo carmine and methylene blue are avid for the loose areolar connective tissue of the submucosa, staining this layer blue. This is very helpful to confirm that one is working in the correct tissue plane. The dye is not taken up by the muscularis propria and thus if this plane is entered a disruption to the almost uniformly blue appearance will be seen.

3 Dilute epinephrine in a concentration of 1:100,000 is also added to the injection solution. It has no role in preventing delayed bleeding but is useful for creating a bloodless field during EMR analogous to its use in cutaneous surgery. Small amounts of bleeding during the resection disrupt the endoscopic view. The epinephrine by its local vaso-constrictive action may also limit dispersion of the submucosal injection solution and thus potentially enhance the magnitude and duration of tissue elevation. TECHNIQUE General Principles The goal of endoscopic resection is to remove the entire lesion in as few pieces as is safely possible. For lesions of maximum dimension mms in the right colon and mms in the left colon (particularly rectum), en-bloc or Ro resection should be considered, but may not always be technically possible. In the colon a Ro excision should be consistently achievable for lesions <20 mms in maximum dimension. En-bloc resection has many proven and theoretical advantages including more accurate histological assessment, negligible recurrence and potential cure in low risk submucosal invasive disease 15. In the colon, if the depth of SMI is <1000 microns (termed SM1), the tumour is histologically well differentiated and there is no lymphovascular invasion then a Ro endoscopic excision is curative Injection Technique The first few submucosal injections set the stage for a successful procedure and great care should be taken at this point. Poorly placed or excessive injections, particularly within relatively narrow lumens (eg. stenosing sigmoid diverticular disease) may create major difficulties and potentially render the procedure impossible. A carefully placed submucosal injection should make the procedure easier by lifting the lesion out into the lumen and towards the colonoscope. This is particularly important for poorly accessible lesions located on the proximal sides of folds or within tight angulations. A transparent short cap can be used to deflect folds and facilitate access to the proximal aspect of lesions saddling folds. For extensive piecemeal ER we prefer a sequential inject and resect technique and thus avoid elevating the entire lesion at the outset. We perform one or two resections each 1-2 sequential injections. Elevating the entirety of a large lesion (>40 mms) may create difficulty with access but also excessive tension within the cushion limiting purchase of the snare and decreasing the size of sequential piecemeal resections. Where access is unrestricted and en-bloc excision is being considered (<25-30 mms distal colon and rectum, <20-25 mm right colon) use the injection to elevate the lesion towards the colonoscope. Divide the lesion into thirds and make the initial injection at the junction of the middle and furtherest thirds (from the scope tip). If SMI is suspected, then avoid intralesional injection and inject on the caecal side. Position the needle tip tangentially to the mucosal surface and gently touch the surface

4 Ask your assistant to commence the injection whilst simultaneously stabbing the mucosa with the needle tip by a rapid 1-2 cm movement with the right hand (holding the injection catheter). This technique accesses the submucosal plane swiftly and accurately. The correct plane is confirmed by an immediate elevation of the mucosa. Ongoing injection without tissue elevation or intra-luminal fluid escape indicates transmural placement of the needle tip with extra-mural injection. Slowly withdraw the needle and the tissue should elevate. Pull back slightly on the injection catheter or colonoscope, whilst maintaining the position of the needle tip in the submucosal plane. This will reduce the deformity on the mucosal surface and maximise fluid deposition immediately beneath the lesion, limiting dispersion of the fluid cushion beyond the perimeter of the lesion. You may even gently rotate the mucosa (which is impaled on the needle tip) out into the lumen by torque on the endoscope shaft. After satisfactory tissue elevation (usually a 5-8 ml submucosal injection), resect this area first. In cases of submucosal fibrosis (usually from a previous attempt, sometimes aggressive biopsy and occasionally lesion biology or SMI) where the needle tip is placed correctly, but the submucosal plane is obliterated by fibrosis, a jet sign may be seen. A jet of fluid exits the lesion at high pressure. Alternatively a canyoning effect may occur where the lesion remains anchored in its original position, but the tissue of the perimeter elevates. The injection should be terminated immediately. The peripheral elevation will make the lesion very difficult to access, ensnare and completely remove. For more extensive lesions, beyond or straddling haustral folds or angulations, plan to resect the least accessible area first and use the first injection to facilitate access to this area. Resection Technique After careful lesion assessment, an endoscopic resection plan is loosely formulated, taking into account the orientation, size and position of the lesion in relation to the endoscope and its location in the colon. A more aggressive approach can usually be adopted in the rectum, whereas great care needs to be taken in the caecum. Plan to remove the lesion in as few pieces as safely possible. En-bloc and oligo piecemeal resections create fewer opportunities for error, more accurate histological assessment and theoretically a reduced risk of recurrence in comparison to when lesions are removed in numerous pieces (poly piecemeal excision). Orientate the target so that it is in the 5-6 o'clock position Resect the most inaccessible and difficult aspect first Work sequentially from the point of first entry into the submucosal plane using the edge of the defect as the base for subsequent piecemeal resections Excise a 2-3 mm margin of normal tissue at the edge of the lesion, this eliminates the risk of small amounts of residual tissue at the edge of the defect. These can be difficult to treat.

5 Align the snare at the edge of the advancing mucosal defect to minimise occurrence of tissue islands within the defect. These are difficult to remove subsequently. If a large en-bloc resection is planned, attempt to align the longitudinal axis of the snare with the longest axis of the lesion, this maximises the tissue capture capacity. For lesions which have extended across the lumen this may require pivoting the body of the snare after impacting it s tip. Open the snare completely above your target and push down firmly on the fluid cushion with the up/down control whilst aspirating air. Deflating the lumen reduces colonic wall tension and decreases the footprint of the neoplasm on that wall, maximising tissue capture. Close the snare tightly. If using a spiral or serrated snare, it is not possible to transect ensnared tissue of more than 10 mm diameter without the use of diathermy. Individual snares have different handling characteristics. Endoscopists who perform advanced endoscopic resection should become familiar with the performance characteristics of their preferred snares. We use the 20 mm spiral snare as the general work horse of extended piecemeal and en-bloc EMR. Closing the snare maximally excludes muscularis propria from the captured tissue analogous to the use of rubber band ligation during multi-band mucosectomy in the oesophagus. As endoscopists we prefer to close the snare handle ourselves during the final transection phase. The sensory feedback is invaluable to inform on the safety and efficacy of the excision. Safe tissue capture is confirmed by three manoeuvres 23,24,26 : 1. assess mobility of the ensnared tissue relative to the adjacent colonic wall; the captured tissue should be able to move back and forth quickly and seemingly slide a short distance over the surface of the colon; 2. the degree of closure of the snare handle; for a spiral snare the snare handle should be such that the distance between the thumb and fingers is less than 1 cm; 3. the speed of transection; this phase should be short-lived. The snare is kept tightly closed whilst the foot pedal is depressed. With a microprocessor controlled generator and alternating short cut and coagulation current, between 1-3 pulses transect the tissue. A more prolonged transection phase indicates either potential entrapment of the muscularis propria or deeper neoplastic invasion. In the right colon we generally tap the pedal, essentially cutting the tissue from the colonic wall in a fashion similar to endoscopic submucosal dissection (ESD). Specimen Processing, Post Procedural Care and Endoscopic Follow up All specimens should be retrieved for histological assessment. Commercially available 2-3 cm nets are the best option for multiple specimen retrieval. With very extensive EMR, specimen retrieval can be a challenge and may require several passages of the colonoscope. Specimens larger than 15 mms should be flattened on a cork board and their margins pinned. Pinning of specimens (particularly after en-bloc excision) prevents curling of the tissue within the formalin and facilitates more accurate histological assessment allowing the histopathologist to report on lateral and deep margins of excision.

6 Location of the lesion should be precisely noted to facilitate accurate endoscopic follow up. In the left colon the anatomical location and the precise distance from the anus on withdrawal with a straight scope should be recorded. If the lesion is located beyond the fold in a difficult position to directly visualise this must also be recorded. In the right colon (ascending colon and caecum) it is useful to note the number of folds above the fold of the ileocaecal valve and the orientation with reference to the ileocaecal valve considering the valve as being on the medial wall in the 9 o'clock position. Thus in reference to this, a 6 o'clock position would be the posterior wall of the ascending colon. For sites that will be difficult to localise subsequently such as the transverse or sigmoid colon or medial wall of the distal ascending colon, marking the contra-lateral wall 2-3 cms distal to the ER site (to ensure that the submucosal carbon solution does not contaminate the ER site) with one or two injections of sterile carbon particle suspension is invaluable. It is important to avoid transmural injection as carbon markers have been reported to cause fat necrosis and a localised inflammatory reaction may cloud clinical interpretation after the procedure 30. A 2 step injection technique is preferred. Saline is used to find the submucosal plane and create a small cushion which can then be injected with the carbon suspension 31. After extensive piecemeal EMR, surveillance colonoscopy is undertaken at 4-6 months to directly assess the scar with both high resolution white light and narrow band imaging to look for any residual/recurrent disease which can easily be treated at that time. If there is a residual, this is generally diminutive and unifocal and easily excised/ablated 5. Subsequent to that colonoscopy is repeated annually for the next three years, with direct visualization and biopsy of the scar, with surveillance intervals gradually lengthening subsequent to that. Summary of Colonic EMR, Outcomes and Limitations The optimal technique of piecemeal ER for extensive lesions has not been defined. There is no consensus on whether the entire lesion should be elevated initially or whether a sequential inject and resect approach should be taken. Although normal saline solution is most commonly used, the optimal solution or volume to be injected is not known. The search for the ideal submucosal injection solution continues 22,24,25,36. Complex lesion competencies, which would include extensive ER, have also not been determined. Large LSTs > 30mm are uncommon and require special skills for safe removal 5,37. They are best managed on a tertiary referral basis, but such pathways have not yet been developed or clearly defined 38. Most large studies from tertiary centres report technical success in the order of 100% with few major complications, no deaths and perforation at a frequency of 0-2% 32-35,39. Nearly all suffer from the limitations described above, particularly retrospective design and lack of comprehensive ITT enrolment.

7 CONCLUSION EMR is clearly the primary endoscopic therapy in the management of large lateral spreading tumors (LSTs) and sessile lesions in the colon. Evidence based lesion specific endoscopic treatment algorithms are required. Post procedural care, procedure duration and endoscopic complications are major considerations in the West which influence the approach and favor EMR over ESD for example. Amongst typical referral cases seen at tertiary centres in the West, non granular lesions are uncommon and thus absolute indications for en-bloc resection of larger lesions by ESD, are thus infrequent 5,34,40,48 Japanese experts now also increasingly accept that en-bloc resection is not necessary for most LSTs 49. The last decade has seen major advances in endoscopic resection throughout the entire gastrointestinal tract and particularly the colon Ever more aggressive endoscopic interventions are now possible with minimal disruption to the underlying anatomy or physiology of the patient, shortened recovery and limited interference with usual activities. The future looks promising.