Colorectal cancer is the second leading cause of cancer. Endoscopic Management of Large Sessile Colonic Polyps: Getting the Low Down From Down Under

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1 moendoscopy for classification of colon polyps. Gastroenterology 2010;138: Chiu HM, Chang CY, Chen CC, et al. A prospective comparative study of narrow-band imaging, chromoendoscopy, and conventional colonoscopy in the diagnosis of colorectal neoplasia. Gut 2007;56: Chang CC, Hsieh CR, Lou HY, et al. Comparative study of conventional colonoscopy, magnifying chromoendoscopy, and magnifying narrow-band imaging systems in the differential diagnosis of small colonic polyps between trainee and experienced endoscopist. Int J Colorectal Dis 2009;24: Levine JS, Ahnen DJ. Clinical practice. Adenomatous polyps of the colon. N Engl J Med 2006;355: Robert ME. The malignant colon polyp: diagnosis and therapeutic recommendations. Clin Gastroenterol Hepatol 2007;5: Rodriguez-Diaz E, Bigio IJ, Singh SK. integrated optical tools for minimally invasive diagnosis and treatment at gastrointestinal endoscopy. Robot Comput Integr Manuf 2011;27: Sugumar A, Sinicrope FA. Serrated polyps of the colon. F1000 Med Rep 2010;2: Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 2010;138: Brenner H, Chang-Claude J, Seiler CM, et al. Protection from colorectal cancer after colonoscopy: a population-based, casecontrol study. Ann Intern Med 2011;154: Sawhney MS, Farrar WD, Gudiseva S, et al. Microsatellite instability in interval colon cancers. Gastroenterology 2006;131: Butterly LF, Chase MP, Pohl H, et al. Prevalence of clinically important histology in small adenomas. Clin Gastroenterol Hepatol 2006;4: Amateau SK, Canto MI. Enhanced mucosal imaging. Curr Opin Gastroenterol 2010;26: Terry NG, Zhu Y, Rinehart MT, et al. Detection of dysplasia in Barrett s esophagus with in vivo depth-resolved nuclear morphology measurements. Gastroenterology 2011;140: Qiu L, Pleskow DK, Chuttani R, et al. Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett s esophagus. Nat Med 2010;16: Lovat LB, Johnson K, Mackenzie GD, et al. Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett s oesophagus. Gut 2006;55: Neumann H, Kiesslich R, Wallace MB, et al. Confocal laser endomicroscopy: technical advances and clinical applications. Gastroenterology 2010;139: Backman V, Roy HK. Light-scattering technologies for field carcinogenesis detection: a modality for endoscopic prescreening. Gastroenterology 2011;140: Roy HK, Turzhitsky V, Kim Y, et al. Association between rectal optical signatures and colonic neoplasia: potential applications for screening. Cancer Res 2009;69: Bista RK, Brentnall TA, Bronner MP, et al. Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia. Inflamm Bowel Dis 2011 Feb 23 [Epub ahead of print]. Reprint requests Address requests for reprints to: Hemant K. Roy, MD, Duckworth Professor of Cancer Research, Section of Gastroenterology, NorthShore University HealthSystem, University of Chicago Pritzker School of Medicine, 1001 University Place Suite 326, Evanston Illinois h-roy@northwestern.edu. Conflicts of interest The authors disclose the following: Drs Roy, Goldberg, and Backman are co-founders/share holders of American BioOptics, LLC. Funding Supported in part by grants from the National Institutes of Health (R01CA156186, R01CA128641, U01CA111257) by the AGA Institute /$36.00 doi: /j.gastro Endoscopic Management of Large Sessile Colonic Polyps: Getting the Low Down From Down Under See Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia, by Moss A, Bourke MJ, Williams SJ, et al, on page Colorectal cancer is the second leading cause of cancer and cancer death in the United States. Yet, most colon cancers can be prevented through the detection and removal of premalignant lesions. 1 Colorectal cancer screening and polypectomy have been credited with progressive trends in decreased rate of colorectal incidence. 2 The majority of benign neoplasms detected at screening colonoscopy are small and removed easily with widely employed biopsy-and-snare polypectomy techniques. However, larger flat and sessile lesions are increasingly recognized, predominantly in the proximal colon. 3 Failure to identify these lesions in the past may account for disappointing rates of missed cancers in patients who have undergone prior colonoscopy. 4 Enhancements in endoscopic image acquisition and display along with increased vigilance and improved recognition on the part of the colonoscopist have resulted in higher detection rates of 1867

2 these lesions. Now that we have found them, what do we do? Large, sessile, nonpedunculated lesions are associated with higher rates of high-grade dysplasia and carcinoma and pose challenges for endoscopic eradication. As such, patients with these lesions have been recommended commonly for operative resection, but that standard of practice is undergoing reevaluation and dynamic change. Endoscopic mucosal resection (EMR) is used increasingly for minimally invasive curative resection of benign and early-stage (T1a) malignant lesions throughout the gastrointestinal tract. 5 Multiple series have reported that large colorectal lesions can be safely and effectively managed with EMR However, the quality of supporting evidence has been suboptimal owing to the retrospective nature, singlecenter study design and lack of long-term outcomes. In this month s issue of GASTROENTEROLOGY, an Australian consortium of advanced endoscopists, led by Dr Michael Bourke, 11 provide exciting new outcomes data with their prospective, multicenter, observational trial entitled Endoscopic treatment of advanced colonic mucosal neoplasia: Outcomes of the Australian Colonic Endoscopic (ACE) resection study. In this well-designed and well-executed study, the authors aimed to determine the safety, efficacy and predictors for successful EMR for large sessile colorectal polyps 20 mm in diameter. Lesions were categorized according to 3 criteria: Paris classification, granular or nongranular surface features, and Kudo pit pattern. EMR was performed using the sequential inject and cut technique by a gastroenterologist with substantial prior colonic EMR experience at a high-volume endoscopy referral center. Patients were monitored for complications immediately after the procedure and received a telephone call 14 days later to assess for procedure-related complications. Follow-up colonoscopy results were available in 79% of patients at an interval of 4 12 months. A total of 479 consecutive patients were enrolled within a 2-year period, with a mean age of 68.5 years and mean lesion size of 35.6 mm. The majority of lesions were adenomas located in the right colon. Thirty-three patients had histologically proven lesions with submucosal invasion, 30 of which were detected in the EMR specimens and 3 in surgical specimens where EMR was not attempted. Risk factors for submucosal invasion (ie, unsuitable for curative EMR) were Paris classification 0-IIa c morphology, corresponding to a flat lesion with a depressed component, a nongranular surface, and a Kudo pit pattern type V, corresponding with amorphous, irregular pits. Overall, endoscopic management achieved curative eradication in 89.2% of lesions. Independent predictors for failed EMR included prior incomplete resection, lesions involving the ileocecal valve, and those in a difficult position for resection. Of the 328 patients who underwent follow-up colonoscopy, only 20% were found to have focal residual/recurrent adenoma, of whom 60 (90%) were amenable to complete endoscopic eradication. Risk factors for adenoma recurrence after a successful EMR included lesions 40 mm in diameter and the use of adjunctive argon plasma coagulation for ablation for incomplete resection and residual tissue at initial treatment EMR. Complications included nonspecific abdominal pain in 10 patients (2.1%), postpolypectomy serositis in 7 (1.5%), and bleeding in 14 (2.9%), only 1 of whom presented after 48 hours (on day 10). Perforation occurred in 6 patients (1.3%), 3 of whom were recognized immediately and treated effectively with endoscopic clips. This study should contribute substantively to the evolution of standard of care management of large ( 2 cm) sessile colorectal neoplasia. The study achieves its aims and affirms the safety, efficacy, and predictors of successful endoscopic management of what we call the defiant polyp (ie, those lesions not amenable to standard biopsy or snare polypectomy techniques). Last, it improves the quality of supporting evidence for broad applicability. Similar outcomes should be achievable by dedicated adopters employing a uniform technique of lesion inspection, classification, resection, and follow-up. However, this requires dedicated education, training, and commitment to curative resection. The EMR technique employed here has been adopted by practitioners in many endoscopy referral centers around the United States. However, the skill sets for advanced EMR are not possessed by all endoscopists. Who, where, and when should EMR be performed when a defiant polyp is identified at screening, surveillance, or diagnostic colonoscopy? A prior incomplete resection attempt markedly decreased the success rate of EMR (74.5%) compared to a treatment- naïve lesion (91.0%) and was associated with technical difficulty with higher rates of submucosal fibrosis, non-lifting, incomplete snare resection and the need for adjunctive ablative therapy. Therefore, an important take-away point from this study is how to address the large, sessile lesion upon initial identification. Given the increased procedure-related time, risk, and skill required for curative EMR, the undertaking is not well suited when discovered initially during a routine colonoscopy. Rather, the lesion should be photographed and its location documented in reference to readily distinguishable colonoscopy landmarks. A limited number of cold forceps biopsies should be obtained without the use of electrosurgical energy to document the histopathology and assess for apparent carcinoma. Lesions deemed difficult to rediscover should be tattooed. However, the tattooing agent should not be injected beneath or directly adjacent to the lesion. Although cold forceps biopsy may sometimes elicit a reparative fibroinflammatory response, it does so far less than that by the introduction of thermal therapies and submucosal injectates. Once the histopathology is reviewed, 1868

the patient can be engaged in an informed discussion of the options for management, including operative resection and dedicated endoscopic resection.

3 the patient can be engaged in an informed discussion of the options for management, including operative resection and dedicated endoscopic resection. The endoscopists in this study were trained in colonic EMR and had considerable prior experience at highvolume endoscopy referral centers. Moreover, they adopted the use of a uniform morphologic grading system to determine lesion suitability and were committed to achieving curative resection for suitable lesions. These results come only with the enlistment of education, training and experience. Practitioners must know when to say go and when to say no. Colonic EMR is now consid- Figure 1. Flat and sessile lesions limited to the mucosa are suitable for curative endoscopic resection. Most lesions greater than 2 cm in diameter will require piecemeal resection. (1) Initial injection of a saline solution into the submucosal layer begins to lift the lesion onto a cushion. (2) Additional submucosal saline injections to lift the entire lesion can be done initially or incrementally. (3 5) Piecemeal, electrocautery, snare resection is performed incrementally to resect the entire lesion and to include a small collar of surrounding normal mucosa to best ensure complete eradication. 1869

ered part of advanced endoscopy fellowship training, but only limited exposure to EMR is obtained in most general gastroenterology fellowships.

4 ered part of advanced endoscopy fellowship training, but only limited exposure to EMR is obtained in most general gastroenterology fellowships. For clinicians removed from fellowship training, colon EMR represents a build-on skill that may be enhanced through attending didactic and hands-on training courses. American endoscopists have been reluctant to adopt complex morphologic characterization schemes such as those used in this study. To simplify, the lesions least suitable for curative EMR are those with a central depression and loss of regular surface pattern. Still, most of these lesions can undergo curative eradication if they lift upon introduction of a submucosal saline injection. In fact, the curative resection rates presented in this study are artificially low, because lesions that demonstrated the non-lifting sign and deemed unsuited for EMR on that basis were considered failures. Persistence, perseverance, and creativity are often required to achieve curative eradication of large sessile colonic lesions, particularly when the lesion is in a challenging location. Changing to a different caliber endoscope, changing the patient s position, and operating with the scope tip in the retroflexed position are all techniques that may be employed to enable complete eradication. The endoscopist and setting should also be appropriate to recognize and manage bleeding and perforation. A nuance in this study worth emphasizing is their predilection for piecemeal over attempted en bloc resection (Figure 1). En bloc resection of larger lesions was associated with decreased focal residual adenoma at follow-up colonoscopy, but also with increased perforation. Most lesions in this study were not suited to en bloc resection owing to size, but the preference for smaller individual resectates may account for their surprisingly low bleeding rates. This consortium favors taking a collar of normal surrounding mucosa at the margins of the neoplasm in contrast to others who employ liberal use of adjunctive ablative therapy. This may account for their favorable findings at follow-up colonoscopy. They use a combination of standard and then stiffer mini snares to preferentially resect away any recognizable focal residual adenoma during the initial effort at complete eradication. The authors bravely disclose the limited use of diathermy ablation using the tip of the snare for focal residual tissue. This long-vilified technique, albeit unsubstantiated, is often used but rarely disclosed and merits further investigation for safety and efficacy. The presence of focal residual/recurrent adenoma at the prior resection site underscores the need to ensure follow-up surveillance colonoscopy. The optimal intervals are suggested in this study and individualized based on those parameters and the histopathologic findings in the resected specimen. Based on direct communication with the study leader, all patients were advised to stop aspirin and antiplatelet activating agents 7 days before the procedure and resumed 5 days postprocedure. Warfarin was managed in concordance with current American Society for Gastrointestinal Endoscopy guidelines. 12 The delayed bleeding rates observed in this study are considerably lower than those observed in our experience. 13 The study leader indicates they used an ERBE VIO 300 electrosurgical generator (Erbe USA, Marietta, GA) with a setting of Endocut Q effect 3 in this series. Studies are underway to assess optimal electrosurgical energy for EMR of large, sessile, colonic lesions. It is encouraging to note that normal saline solution, tinted with a chromic agent, sufficed as the injectate. It is inexpensive and widely available. Moreover, the prospects for designer agents getting approval from the US Food and Drug Administration for this purpose are daunting. Curative EMR for large, sessile colorectal lesions compares favorably with operative resection, is more costeffective, and is associated with less morbidity and mortality. It is an anathema that advanced colonic EMR is not adequately reimbursed for the technical and time demands of the procedure. 14 Presently, there is no unique Current Procedural Terminology code for this technique. This study provides data quantifying the amount of time required based on lesion size. The mean procedure duration was 25 minutes, and each increase in size of approximately 10 mm added an additional 8 10 minutes for the procedure, but this in expert hands with experienced staff. In endoscopy referral centers, colonic EMR is a safe and effective procedure for selected large, flat, and sessile colorectal lesions. Most lesions can be cured with colonoscopic management, and it is generally a preferred alternative to operative resection. Failed endoscopic management at an endoscopy referral center on the basis of lesion assessment or inability to achieve complete eradication does not preclude operative resection. Practitioners performing routine colonoscopy should continue to increase their skill in detecting flat and sessile lesions, particularly right colon lesions. Attempt at resection should be resisted unless the lesion is deemed suitable for complete eradication at the setting and within the scope of the procedure conferred during the informed consent process. The opportunity for referral to a practitioner of advanced colonic EMR should be considered with the patient. To replicate the results presented herein, practitioners of advanced colon EMR must carefully assess the lesion for suitability and be committed to achieving curative resection. The importance of follow-up surveillance examinations must be emphasized at the outset. Education and training are needed to expand availability while maintaining quality and issues regarding reimbursement should be revisited to reflect the evolution in practice. 1870

5 Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Gastroenterology at and at doi: /j.gastro VINAY CHANDRASEKHARA GREGORY G. GINSBERG University of Pennsylvania School of Medicine Philadelphia, Pennsylvania References 1. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 2008; 134: Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on the status of cancer, , featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 2010;116: Soetikno RM, Kaltenbach T, Rouse RV, et al. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA 2008;299: Baxter NN, Goldwasser MA, Paszat LF, et al. Association of colonoscopy and death from colorectal cancer. Ann Intern Med 2009;150: ASGE Technology Committee, Kantsevoy SV, Adler DG, et al. Endoscopic mucosal resection and endoscopic submucosal dissection. Gastrointest Endosc 2008;68: Arebi N, Swain D, Suzuki N, et al. Endoscopic mucosal resection of 161 cases of large sessile or flat colorectal polyps. Scand J Gastroenterol 2007;42: Su MY, Hsu CM, Ho YP, et al. Endoscopic mucosal resection for colonic non-polypoid neoplasms. Am J Gastroenterol 2005;100: Mahadeva S, Rembacken BJ. Standard inject and cut endoscopic mucosal resection technique is practical and effective in the management of superficial colorectal neoplasms. Surg Endosc 2009;23: Luigiano C, Consolo P, Scaffidi MG, et al. Endoscopic mucosal resection for large and giant sessile and flat colorectal polyps: a single-center experience with long-term follow-up. Endoscopy 2009;41: Ferrara F, Luigiano C, Ghersi S, et al. Efficacy, safety and outcomes of inject and cut endoscopic mucosal resection for large sessile and flat colorectal polyps. Digestion 2010;82: 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: Zuckerman MJ, Hirota WK, Adler DG, et al. ASGE guideline: the management of low-molecular-weight heparin and nonaspirin antiplatelet agents for endoscopic procedures. Gastrointest Endosc 2005;61: Ahmad NA, Kochman ML, Long WB, et al. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointest Endosc 2002;55: Swan MP, Bourke MJ, Alexander S, et al. 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 (with videos). Gastrointest Endosc 2009;70: Reprint requests Address requests for reprints to: Gregory G. Ginsberg, MD, Hospital of the University of Pennsylvania, Gastroenterology Division, 3rd floor Ravdin Building, 3400 Spruce St., Philadelphia, PA gregory.ginsberg@uphs.upenn.edu. Conflicts of interest The authors disclose no conflicts by the AGA Institute /$36.00 doi: /j.gastro Is MELD Fit Enough? See A revised model for end-stage liver disease optimizes prediction of mortality among patients awaiting liver transplantation, by Leise MD, Kim WR, Kremers WK, et al, on page The Model for End-Stage Liver Disease (MELD) score was introduced in February 2002 as the means for ranking liver transplant candidates based solely on objective determinants. The MELD score was developed in response to inequities in liver allocation that developed over the preceding decade. 1,2 Specifically, prioritization was based previously on waiting time and subjective clinical variables, neither of which accurately reflected the medical need for transplantation. Consequently, critically ill patients died waiting for a liver, while less sick patients were preferentially transplanted. With implementation of MELD, a mathematical formula predictive of 90-day mortality, prioritization of liver candidates improved. The most obvious benefit was a drop in waiting list mortality along with removal of well-compensated patients from the waiting list. 3,4 However, the need for ongoing revision of MELD was recognized from its inception: Basing organ allocation on a system that has been derived from a much more evidence-based approach 1871

One of the major frontiers of translational gastroenterological

One of the major frontiers of translational gastroenterological Editorials Colonoscopy and Optical Biopsy: Bridging Technological Advances to Clinical Practice See Endoscopic trimodal imaging detects colonic neoplasia as well as standard video endoscopy, Kuiper T,