SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. References

See article in J. Gastroenterol. Hepatol. 2011; 26: 1619–1625.

The last decade has seen major advances in the endoscopic treatment of advanced mucosal neoplasia. Curative wide field endoscopic resection (ER) for superficial lesions greater than 100 mm, and possibly even circumferential is now reproducibly undertaken in expert centers around the world.11–3 Complete, safe, single session removal of all neoplastic tissue is the primary objective of endoscopic resection. Although not always feasible, this is attempted with the technical goal of en-bloc excision and, as a corollary, a histologically complete resection with free lateral and deep margins (RO) specimen is achieved. This approach has several advantages. They include negligible recurrence, more accurate histological assessment and reduced endoscopic surveillance requirements, translating to substantial cost savings and improved patient compliance.4 It also provides definitive T staging and thus stratification for the risk of lymph node metastasis in cases where submucosal invasion (SMI) exists. In low risk SMI (superficially invasive well differentiated tumor without lymphovascular involvement) ER may be seen as effective treatment, particularly in elderly patients with significant co-morbidity or where the anatomical site necessitates high risk or physiologically disruptive surgery.5,6 Simply put, the small probability of lymph node metastasis is exceeded by the risk of perioperative mortality or disabling long term morbidity and digestive dysfunction.

In this issue of the Journal, Drs Kim and colleagues from Seoul National University College of Medicine retrospectively describe the outcome of 129 patients with relatively small (85% < 20 mm) early colorectal cancers of which 90% were treated by endoscopic mucosal resection (EMR).7 80% of lesions were located in the rectosigmoid and 61% were classed as sessile. There was an equal distribution of intramucosal cancer and submucosal invasive neoplasia. 122 patients were treated by endoscopy alone. Importantly, the outcomes for pedunculated lesions with or without SMI was in keeping with the established published reports.8,9 The sessile lesion cohort provides the most interest, although follow up is relatively short. All patients with intramucosal cancer, irrespective of whether lateral margins were free of disease, showed no recurrence during mean follow up of 19 months. In contrast to other mucosal sites, the mucosal layer of the colon does not contain lymphatics, so as expected, provided histological assessment is accurate, and endoscopic follow up is careful, these patients do not require surgical treatment.2

What about the invasive lesions? Can ER outcomes be improved even further? The threshold for safe en bloc excision with conventional EMR is 20 mm and as much as 25 mm in the rectum or stomach. The alternative, endoscopic submucosal dissection (ESD), reliably achieves en-bloc resection. Pioneered in the stomach, a large body of evidence from Japanese and Korean endoscopists has been accumulated. In these nations where the prevalence of gastric cancer is extraordinarily high and population-based endoscopic screening exists, early disease accounts for up to 50% of the disease burden. Thus, ESD to achieve a RO resection is seen as the treatment of choice for early disease, even if superficial SMI is present, provided the lesion is well differentiated, lymphovascular invasion is absent and margins are clear. Given the disruptive and hazardous nature of gastric surgery, ER is considered effective treatment.6 In the colon, however, ESD has inherent limitations. In comparison to EMR these include substantially greater risk of perforation, a three- to four-fold increase in procedure time and the necessity for post-procedural admission.4,10 (Fig. 1) In addition, the incremental benefit of en bloc excision in low risk SMI disease is marginal as the risks of colonic surgery are minimal for most patients. In contrast to the colon, esophageal or gastric surgery carries with it a major perioperative mortality risk and the prospect of long term digestive dysfunction. Colonic ESD is technically challenging, particularly for western endoscopists who are unable to acquire these skills during their training due to the absence of the comparatively safer early gastric lesions. ER of these technically less demanding gastric lesions is an established component of endoscopy training programs in East Asia. A logical recourse is to consider that simple modifications of snare-based techniques may increase en bloc resection size beyond these accepted limits and enhance EMR outcomes.

image

Figure 1. Comparison of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).

Download figure to PowerPoint

Yet even if en bloc resection cannot be achieved, excising the lesion in as few pieces as safely possible leads to the most favorable technical and clinical outcomes. It is instructive to consider the concept of the total perimeter of excision (TPE) as follows: Each snare based resection is an opportunity for error at the point of tissue capture by the snare whether due to incomplete excision (under treatment), potentially leading to recurrence or deep thermal injury (over treatment), which risks transmural injury with either serositis or delayed perforation. As most lesions are roughly circular, lesion perimeter is calculated as 2 π r (where r is the radius of the lesion). Thus, for any lesion of a given size, the TPE will be least for en bloc specimens, of intermediate value for oligo-piecemeal resections and greatest for poly-piecemeal excisions. As TPE increases, the opportunity for error increases in direct proportion.

Endoscopic mucosal resection outcomes may be enhanced by altering the injection solution or modifying snare resection technique. A blinded in vivo large animal trial has shown that altering the submucosal injectant from the conventional normal saline to a colloidal solution, such as succinylated gelatin, confers a more than 40% increase in en bloc resection size.11 Large lesions are removed by extended piecemeal EMR. One means of comparing resection efficacy for lesions of varying sizes has been termed the Sydney resection quotient (SRQ). This is defined as the size of lesion divided by the number of pieces to resect.12 For example a large 40 mm lesion removed in a single piece renders a SRQ of 40 whereas this lesion removed in eight pieces renders a value of 5. In a double blind human trial of 80 patients with sessile colonic lesions 20 mm and greater, succinylated gelatin use doubled the SRQ and halved the procedure time from 24 to 12 min.12

Circumferential submucosal incision (CSI) EMR is another modification that enhances en bloc resection rates. It incorporates the ESD strategy of circumferential submucosal dissection to isolate the lesion ensuring free lateral margins, and then a snare is used to complete the resection. Freeing the lateral margins allows greater elevation of the target tissue, and incorporation of the snare to achieve the final excision avoids the time consuming and more hazardous mucosal dissection beneath the lesion of conventional ESD. In an in vivo large animal trial, this technique reliably achieved en bloc excision for artificial 40 mm colonic lesions.13 To date, clinical experience is limited.14

Alternatively ESD may be simplified by hybrid knife technology whereby the snare device combines both injection for tissue elevation and cutting without instrument exchange.15 This is a significant advance particularly for western endoscopists who are less familiar with ESD technique. Because device exchange is not necessary, there are fewer tendencies to under-inject the submucosa and the cutting plane can be readily expanded with fluid, making dissection safer and more efficient. The ability to readily inject instantly widening the plane of safe dissection substantially enhances safety. This is important for ESD novices, who are likely less capable of readily identifying the respective tissue planes at the dissection interface and less precise with their cuts.

So can en bloc resection, whether by enhanced EMR or ESD reliably cure low risk submucosal invasive disease in the colon? First, is it low risk disease? Careful histological review is always required in these cases. In clinical practice, it is often difficult to accurately measure the depth of invasion. Colonic specimens not uncommonly contain less than 1000 microns of submucosa, this being the SM one (low risk) threshold.2 This compromises interpretation.

Second, could there be lymph node metastasis? In the Kim series, 58 patients with SMI were treated endoscopically; four or almost 8% had recurrent disease in less than 3 years. Two of these were low risk. As the Authors explain, the risk of non-operative management was explained to these patients. These patients may yet be cured, but the outcome is not assured and a valuable opportunity has potentially been lost. Patients with low risk well-differentiated margin-free invasive colonic disease discovered after successful endoscopic resection should be discussed at a multi-disciplinary team meeting. The probability of lymph node metastasis must be weighed against the low perioperative risk, the potential for long term morbidity (e.g. stoma), and the patient's wishes. If the patient has invasive cancer, rather than accept a treatment that may “suffice” we must as clinicians always ask ourselves “what more can we reasonably do to ensure that this invasive cancer is cured?” When SMI disease is found in a sessile colonic lesion and perioperative risk is low, surgery must always be strongly considered.

References

  1. Top of page
  2. Abstract
  3. References
  • 1
    Pech O, Behrens A, May A et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus. Gut 2008; 57: 12006.
  • 2
    Moss A, Bourke MJ, Williams SJ et al. Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia. Gastroenterology 2011; 140: 190918.
  • 3
    Swan MP, Bourke MJ, Alexander S, Moss A, Williams SJ. Large refractory colonic polyps: is it time to change our practice? A prospective study of the clinical and economic impact of a tertiary referral colonic mucosal resection and polypectomy service. Gastrointest. Endosc. 2009; 70: 112836.
  • 4
    Bourke MJ. Current status of colonic endoscopic mucosal resection in the West and the interface with endoscopic submucosal dissection. Dig. Endosc. 2009; 21: S2732.
  • 5
    Ono H, Kondo H, Gotoda T et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut 2001; 48: 2259.
  • 6
    Jee YS, Hwang SH, Rao J et al. Safety of extended endoscopic mucosal resection and endoscopic submucosal dissection following the Japanese Gastric Cancer Association treatment guidelines. Br. J. Surg. 2009; 96: 115761.
  • 7
    Kim MN, Kang JM, Yang JI et al. Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection. J. Gastroenterol. Hepatal. 2011; 26: 161925.
  • 8
    Doniec JM, Lohnert MS, Schniewind B. Endoscopic removal of large colorectal polyp: prevention of unnecessary surgery? Dis. Colon Rectum 2003; 46: 3408.
  • 9
    Uraoka T, Saito Y, Matsuda T, Ikehara H, Gotoda T, Saito D. Fujii The endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum. Gut 2006; 55: 15927.
  • 10
    Saito Y, Uraoka T, Matsuda T et al. Endoscopic treatment of large superficial colorectal tumors: a case series of 200 endoscopic submucosal dissections (with video). Gastrointest. Endosc. 2007; 66: 96673.
  • 11
    Moss A, Bourke MJ, Kwan V et al. Succinylated gelatin substantially increases en bloc resection size in colonic EMR: a randomised blinded trial in a porcine model. Gastrointest. Endosc. 2010; 71: 58995.
  • 12
    Moss A, Bourke MJ, Metz AJ. A randomized, double-blind trial of succinylated gelatin submucosal injection for endoscopic resection of large sessile polyps of the colon. Am. J. Gastroenterol. 2010; 105: 237582.
  • 13
    Moss A, Bourke MJ, Tran KL, Godfrey C, McKay G, Chandra AP. Lesion isolation by circumferential submucosal incision prior to EMR (CSI-EMR) substantially enhances en bloc resection rates for 40 mm colonic lesions. Endoscopy 2010; 42: 15.
  • 14
    Repici A, Conio M, De Angelis C et al. Insulated-tip knife endoscopic mucosal resection of large colorectal polyps unsuitable for standard polypectomy. Am. J. Gastroenterol. 2007; 102: 161723.
    Direct Link:
  • 15
    Yahagi N, Neuhaus H et al. Comparison of standard endoscopic submucosal dissection (ESD) versus an optimized ESD technique for the colon: an animal study. Endoscopy 2009; 41: 3405.