Underwater EMR without submucosal injection: Is less more?

Abstract

Conventional injection-assisted EMR is well established as the preferred method for the removal of sessile colonic polyps. Submucosal injection is based on the rationale that a fluid “cushion” separates the superficial mucosa-based lesion from the underlying muscular layer, thus protecting against perforation and transmural thermal injury when snare resection is performed. The 2015 ASGE Technology Status Evaluation Report on EMR states, “The cushion lifts the lesion, facilitating capture and removal by using a snare while minimizing mechanical or electrocautery damage to the deeper layers of the GI wall.”1Hwang J.H. Konda V. Barham K. et al.ASGE Technology CommitteeEndoscopic mucosal resection.Gastrointest Endosc. 2015; 82: 215-226Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar This practice has disseminated to become the standard of care despite an absence of studies proving its clinical benefit. In fact, only a single small animal study compared the depth of thermal injury after snare resection with and without submucosal saline solution injection in 6 swine. The results were mixed: Submucosal saline solution injection significantly reduced the proportion of lesions with deep injury after treatment with argon plasma coagulation and heat probe but not with hot biopsy forceps or a bipolar device (Goldprobe).2Norton I.D. Wang L. Levine S.A. et al.Efficacy of colonic submucosal saline solution injection for the reduction of iatrogenic thermal injury.Gastrointest Endosc. 2002; 56: 95-99Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar Can submucosal injection increase the risk of EMR? Perhaps—if the injection is misguided into deeper tissue planes. Inadvertent transmural injection of India ink for tattoing is not uncommon and can result in a host of adverse events.3Ghersin I. Sroka G. Haj B. et al.Inadvertent tattooing of adjacent large bowel: a case report and review of literature.Arq Bras Cir Dig. 2014; 27: 161-162Google Scholar What we refer to as postpolypectomy syndrome, attributed to a transmural burn from electrocoagulation, may as much be due to extramural injection. When present, the lifting sign may not be a reliable indicator of injection into the submucosal layer; injection into the connective tissue space between the circular and longitudinal muscle layers may cause lifting of the circular layer, with subsequent risk of snare capture of this layer. Apart from potentially increasing risk, submucosal injection may technically complicate snare resection in several ways. Conceptually, submucosal injection should facilitate snare resection by raising a sessile or flat lesion relative to the surrounding mucosa. However, loose connective tissue in the submucosal plane allows fluid to readily spread to the surrounding perilesional area. In this manner, injection may paradoxically flatten the lesion or even result in relative lesion depression. Fluid injection also increases the submucosal tissue tension, which may hinder snare engagement of the submucosa. The snare may slip or slide off as the snare is closed. Poorly executed injection may displace the lesion into a less-accessible location or may restrict operating luminal space as a result of the submucosal bulge, thus hampering access to the lesion. Occasionally, submucosal injection can also result in back-bleeding at the injection site, which can hinder visibility and trigger peristalsis. Finally, injection may also reduce therapeutic and clinical efficacy by increasing the lesion area and need for piecemeal rather than en bloc resection. Submucosal injection through the neoplastic lesion may theoretically spread or seed neoplastic cells along the submucosa and into deeper tissue layers of the colonic wall. This may contribute to recurrence after an initial complete, seemingly curative resection. Needle tract seeding from FNA procedures is well documented among various tumor types. A systematic review found a 2.7% overall incidence of needle tract tumor seeding after hepatocellular carcinoma FNA. Prior FNA of hilar cholangiocarcinoma has been shown to be associated with an increased risk of peritoneal metastases and may render a patient ineligible for liver transplantation. Tumor seeding has also been reported after perforations resulting from EMR and endoscopic submucosal dissection (ESD) or after full-thickness resections.4Gleeson F.C. Lee J.H. Dewitt J.M. Tumor seeding associated with selected gastrointestinal endoscopic interventions.Clin Gastroenterol Hepatol. 2018; 16: 1385-1388Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Pros and cons of submucosal injection aside, what are the outcomes that we can expect from conventional EMR? Technical success is nearly 100%. Perforation is rare but occurs in 1.5% of cases.5Hassan C. Repici A. Sharma P. et al.Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis.Gut. 2016; 65: 806-820Crossref PubMed Scopus (212) Google Scholar Noteworthy, however, is a high incidence of residual or recurrent neoplasia, averaging 22% after piecemeal resection of lesions over 20 mm.6Belderbos T.D. Leenders M. Moons L.M. et al.Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis.Endoscopy. 2014; 46: 388-402Crossref PubMed Scopus (210) Google Scholar Although often diminutive when surveillance colonoscopy is performed at a short interval after the index resection, a recurrent lesion necessitates a repeated attempt at removal by resection or thermal ablation and another subsequent short-interval surveillance, contributing to significant increased cost and burden on patients. Defiant lesions will require eventual surgical intervention. The primary predictor of recurrence is the performance of piecemeal resection.6Belderbos T.D. Leenders M. Moons L.M. et al.Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: systematic review and meta-analysis.Endoscopy. 2014; 46: 388-402Crossref PubMed Scopus (210) Google Scholar Another predictor of recurrence is the use of thermal ablation (argon plasma coagulation) for residual neoplasia.7Moss A. Bourke M.J. Williams S.J. et al.Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia.Gastroenterology. 2011; 140: 1909-1918Abstract Full Text Full Text PDF PubMed Scopus (436) Google Scholar This high recurrence rate after piecemeal EMR is a critical shortcoming and has generated growing enthusiasm for ESD as a method of achieving en bloc removal of large polyps. However, the higher en bloc resection rates of ESD come at the expense of a significantly higher perforation rate.8Nakajima T. Saito Y. Tanaka S. et al.Current status of endoscopic resection strategy for large, early colorectal neoplasia in Japan.Surg Endosc. 2013; 27: 3262-3270Crossref PubMed Scopus (172) Google Scholar In addition, the practical barriers to dissemination of ESD remain prohibitive: ESD has a steep learning curve and is very labor intensive and time consuming, especially in the colon, where endoscope handling and control are more difficult.9Tanaka S. Kashida H. Saito Y. et al.JGES guidelines for colorectal endoscopic submucosal dissection/endoscopic mucosal resection.Dig Endosc. 2015; 27: 417-434Crossref PubMed Scopus (347) Google Scholar ESD is also more costly than EMR, owing to the need for specialized accessories. Thus, both conventional EMR and ESD are imperfect as resection methods. The endosonographic observation that the mucosa and submucosa float away from the muscularis layer when the colon is filled with water inspired the underwater EMR (UEMR) technique.10Binmoeller K.F. Wilert F. Shah J. et al.“Underwater” EMR without submucosal injection for large sessile colorectal polyps (with video).Gastrointest Endosc. 2012; 75: 1086-1091Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar With water submersion, the mucosa and submucosa form multiple involutions resembling rugal folds of the stomach while the deeper muscularis layer remains circular and does not follow the involutions. By removing intraluminal air, colonic wall tension is decreased, and the wall reassumes its native thickness of around 5 mm. Once underwater, tissue buoyancy—due to the fat density of the submucosa and its antigravity effect—will lift overlying adenomatous mucosal lesions away from the muscularis propria, thereby eliminating the need for submucosal injection. Natural wall layer separation reduces the chance of unintentional snare entrapment of the muscularis. Intraluminal water also serves as a heat sink, protecting the deeper colonic wall from thermal injury. In combination, layer separation and thermal dissipation are thought to decrease the risk of early and delayed perforation and of postpolypectomy electrocautery syndrome.11Hsieh Y. Binmoeller K.F. Leung F.W. Su1664 Underwater polypectomy: heat-sink effect in an experimental model.Gastrointest Endosc. 2016; 83: 1Abstract Full Text Full Text PDF PubMed Google Scholar The main advantage of UEMR is that less distension of the bowel lumen potentially allows the capture of a larger mucosal surface area in the opened snare. By folding into the lumen when underwater, large colonic lesions, while having unchanged total surface area and length, will occupy a smaller plot at the colon wall compared with their flattened, more spread-out state, under air insufflation. Despite having a fixed maximum size, a resection snare will thus be able to capture underwater lesions much larger than the snare opening. In our prospective series examining larger lesions, 50 patients with 53 lateral spreading tumors with a median size of 30 mm (range, 20-40 mm) were treated with UEMR.12Binmoeller K.F. Hamerski C.M. Shah J.N. et al.Attempted underwater en bloc resection for large (2-4 cm) colorectal laterally spreading tumors (with video).Gastrointest Endosc. 2015; 81: 713-718Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar En bloc resection was possible in 55% of patients with a 33-mm snare. Water immersion also reduced haustral folds, making “clamshell” lesions that straddle both sides of a fold appear planar, enabling en bloc resection. Other investigators have reported similarly high en bloc resection rates. In a retrospective study comparing UEMR with conventional EMR, UEMR was associated with a higher rate of complete macroscopic resection (98.6% vs 87.1%, P = .012) and lower rates of adenomatous recurrence for lesions ≥15 mm.13Schenck R.J. Jahann D.A. Patrie J.T. et al.Underwater endoscopic mucosal resection is associated with fewer recurrences and earlier curative resections compared to conventional endoscopic mucosal resection for large colorectal polyps.Surg Endosc. 2017; 31: 4174-4183Crossref PubMed Scopus (49) Google Scholar Upon initial follow-up, recurrent adenoma was found in 7.3% of cases after UEMR but in 28.3% after conventional EMR (odds ratio 5.0). Interim results of an international multicenter randomized controlled trial comparing injection-assisted versus underwater EMR for the treatment of 219 large colorectal laterally spreading tumors demonstrated a significantly higher en bloc resection rate for UEMR (51% vs 25%, P = .001) and significantly fewer additional ablative techniques (11% vs 26%, P = .006).14Hamerski C.M. Wang A. Amato A. et al.Injection-assisted versus underwater endoscopic mucosal resection without injection for the treatment of colorectal laterally spreading tumors: interim analysis of an international multicenter randomized controlled trial [abstract].Gastrointest Endosc. 2018; 87: AB55-AB56Abstract Full Text Full Text PDF Google Scholar Thus, UEMR safely enabled the en bloc removal of over 50% of lesions >2 cm with a single ensnarement, which challenges current societal guidelines recommending piecemeal EMR for lesions >2 cm.15Ferlitsch M. Moss A. Hassan C. et al.Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.Endoscopy. 2017; 49: 270-297Crossref PubMed Scopus (529) Google Scholar Since the initial report of UEMR in 2012,10Binmoeller K.F. Wilert F. Shah J. et al.“Underwater” EMR without submucosal injection for large sessile colorectal polyps (with video).Gastrointest Endosc. 2012; 75: 1086-1091Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar several additional series have reported successful safe and efficacious application of the UEMR technique for large colonic lesions. In this issue of Gastrointestinal Endoscopy, Spadaccini et al16Spadaccini M. Fuccio L. Lamonaca L. et al.Underwater EMR for colorectal lesions: a systematic review with meta-analysis (with video).Gastrointest Endosc. 2019; 89: 1109-1116Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar provide a systematic review with meta-analysis of the literature. Ten studies, including 7 prospective, were eligible for analysis, providing data on 508 lesions. The meta-analysis highlights 2 important suggested advantages of UEMR: (1) high en bloc resection rates and (2) low residual/recurrence rates. The 2 are interlinked because piecemeal resection has been identified as the key risk factor for lesion recurrence. A funnel plot on each of these 2 outcomes was not included but would strengthen their validity by excluding the effect of publication bias. One weakness of the meta-analysis is the inclusion of studies with substantial heterogeneity in the target lesions resected. Ideally, one would like to see a breakdown by size, location, histology, and prior instrumentation of the lesion. The studies included UEMR of lesions that may qualify as “difficult” with the use of conventional EMR, either by location such as at the appendiceal orifice,17Binmoeller K.F. Hamerski C.M. Shah J.N. et al.Underwater EMR of adenomas of the appendiceal orifice (with video).Gastrointest Endosc. 2016; 83: 638-642Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar or by recurrence after a prior attempt at piecemeal resection.18Kim H.G. Thosani N. Banerjee S. et al.Underwater endoscopic mucosal resection for recurrences after previous piecemeal resection of colorectal polyps (with video).Gastrointest Endosc. 2014; 80: 1094-1102Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Difficult lesions represented >10% of the lesions included in the meta-analysis. The pooled outcomes of UEMR were favorable in spite of this inclusion. The meta-analysis does not include several outcome variables of interest pertinent to UEMR. One is resection time, which is suggested to be shorter with UEMR because of the elimination of submucosal injection and a higher rate of en bloc resection. Another is the incidence of invasive cancers on surgical pathologic analysis. A potential drawback of UEMR is the lack of the “nonlifting sign” (NLS), which may be a sign of an invasive malignancy. However, the Japanese literature has amply demonstrated that a cancer invading into the submucosa may lift, and a benign adenoma with submucosal fibrosis may not lift. A multicenter study in Japan showed that 10 of 26 lesions with invasive cancers into the submucosa (beyond 1000 μm) had a false-negative NLS and that endoscopic diagnosis was more reliable than NLS.19Kobayashi N. Saito Y. Sano Y. et al.Determining the treatment strategy for colorectal neoplastic lesions: endoscopic assessment or the non-lifting sign for diagnosing invasion depth?.Endoscopy. 2007; 39: 701-705Crossref PubMed Scopus (113) Google Scholar At the very least, this meta-analysis emphasizes that UEMR challenges the need for submucosal injection before EMR, a methodologic standard propagated by habit and convention but resting on few data for its purported advantages. With UEMR, elimination of an unnecessary procedural step alone has numerous theoretical advantages. The promise of achieving higher en bloc resection rates and lower recurrence rates, highlighted by the meta-analysis, are important potential advantages that await validation in randomized controlled trials comparing UEMR with conventional EMR. The author disclosed no financial relationships relevant to this publication. Underwater EMR for colorectal lesions: a systematic review with meta-analysis (with video)Gastrointestinal EndoscopyVol. 89Issue 6PreviewUnderwater EMR is an alternative way to have nonpedunculated colorectal lesions lifted before being resected. The endoscopist takes advantage of the behavior of mucosal lesions floating away from the muscular layer, once immersed in liquid. We performed a systematic review with meta-analysis to evaluate the efficacy and safety of this technique. Full-Text PDF