Are We Ready to Embrace Endoscopic Submucosal Dissection as the Organ-Sparing, Minimally Invasive Endoscopic Surgical Procedure of Choice for Large Colorectal Adenomas and Early Cancers?

Abstract

See “Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan,” by Ohata K, Kobayashi N, Sakaj E, et al, on page 1423. Endoscopic submucosal dissection (ESD) is an endoscopically guided, minimally invasive, surgical technique to treat superficial tumors and precancerous and early cancerous lesions in the gastrointestinal (GI) tract.1Saito Y. Fujii T. Kondo H. et al.Endoscopic treatment for laterally spreading tumors in the colon.Endoscopy. 2001; 33: 682-686Crossref PubMed Scopus (144) Google Scholar, 2Bhatt A. Abe S. Kumaravel A. et al.Indications and techniques for endoscopic submucosal dissection.Am J Gastroenterol. 2015; 110: 784-791Crossref PubMed Scopus (85) Google Scholar, 3Lee E.J. Lee J.B. Lee S.H. et al.Endoscopic submucosal dissection for colorectal tumors—1,000 colorectal ESD cases: one specialized institute’s experiences.Surg Endosc. 2013; 27: 31-39Crossref PubMed Scopus (120) Google Scholar Despite the advantages of ESD over other resection techniques for large colorectal lesions, this technique has been slow to enter clinical practice in many parts of the world. Nonetheless, during the last few years, ESD has rapidly expanded in the West and Southern Hemisphere.4Yamada M. Saito Y. Takamaru H. et al.Long-term clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms in 423 cases: a retrospective study.Endoscopy. 2017; 49: 233-242Crossref PubMed Scopus (60) Google Scholar, 5González N. Parra-Blanco A. Arantes V. et al.Current status of endoscopic submucosal dissection in Latin America.Acta Gastroenterol Latinoam. 2016; 46: 213-219Google Scholar, 6Probst A. Ebigbo A. Märkl B. et al.Endoscopic submucosal dissection for early rectal neoplasia: experience from a European center.Endoscopy. 2017; 49: 222-232PubMed Google Scholar Still, ESD is not as widespread as in Japan and other countries. Whereas technical factors and acquisition of skills may be one reason for this, a big argument still hindering its more widespread acceptance has been the lack of large, prospective observational outcome studies. The solution to this knowledge gap is provided now by the Colorectal ESD Activation Team of Japan (CREATE-J), consisting of 20 academic or tertiary institutions in Japan.7Ohata K. Kobayashi N. Sakaj E. et al.Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan.Gastroenterology. 2022; 163: 1423-1434Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Between February 2013 and January 2015, CREATE-J prospectively and consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. The patients were monitored intensively during a 5-year follow-up. The 1814 lesions had a mean tumor diameter of 32.4 mm, 88.9% were laterally spreading tumors, and more than half were located in the right colon. En bloc resection was achieved in 1759 lesions (97.0%), whereas piecemeal resection was required in 1.9% lesions. Only 1.1% of ESD procedures were discontinued due to technical difficulties or severe intraoperative adverse events. Complete resection was achieved in 1640 lesions (90.4%), and 209 (11.5%) showed lateral margin-positive resection (incomplete resection). The primary outcomes of 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. The authors concluded that a favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms.7Ohata K. Kobayashi N. Sakaj E. et al.Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan.Gastroenterology. 2022; 163: 1423-1434Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The authors are to be commended for performing a large, prospective, multicenter study that provides solid findings. In addition, the study stands out for including large, advanced lesions, and using state-of-the art polyp characterization and resection techniques, which are widely available around the world. A potential drawback of the study is the lack of biopsy of the scar during follow up, but the authors performed careful endoscopic inspection of the postresection sites. Additional drawbacks are the lack of a comparison group and the performance of ESD by experts, which may inflate outcomes, compared with a more general population, while probably reducing adverse events rates. How does this study affect our practice? It is evident that ESD is an efficient technique to achieve complete resection of large colorectal lesions. Second, the favorable results in a very large, prospective follow-up study now underscore the clinical efficacy of this resection method. Some would argue that it is time to perform a prospective study comparing piecemeal endoscopic mucosal resection (p-EMR) with ESD. But is this acceptable? Although both techniques intend for complete removal of the lesion, p-EMR has higher rates of incomplete removal of lesions, and accurate histopathologic evaluation is hindered by the larger number of pieces submitted for analysis.8Adler J. Toy D. Anderson J.C. et al.Metachronous neoplasias arise in a higher proportion of colon segments from which large polyps were previously removed, and can be used to estimate incomplete resection of 10-20 mm colorectal polyps.Clin Gastroenterol Hepatol. 2019; 17: 2277-2284Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 9Klein A. Tate D.J. Jayasekeran V. et al.Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.Gastroenterology. 2019; 156: 604-613.e3Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar, 10Sidhu M. Shahidi N. Gupta S. et al.Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps.Gastroenterology. 2021; 161: 163-170.e3Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 11Nakajima T. Sakamoto T. Hori S. et al.Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.Surg Endosc. 2022; 36: 515-525Crossref PubMed Scopus (3) Google Scholar In a large study from Japan involving 1845 large colon polyps, en bloc ESD was associated with 1.8% local recurrence rate compared with 6.3% for p-EMR.12Oka S. Tanaka S. Saito Y. et al.Colorectal Endoscopic Resection Standardization Implementation Working Group of the Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan.Am J Gastroenterol. 2015; 110: 697-707Crossref PubMed Scopus (177) Google Scholar This study also found that piecemeal resection was the most important risk factor for local recurrence, regardless of the endoscopic resection method used.12Oka S. Tanaka S. Saito Y. et al.Colorectal Endoscopic Resection Standardization Implementation Working Group of the Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan.Am J Gastroenterol. 2015; 110: 697-707Crossref PubMed Scopus (177) Google Scholar In a retrospective study from Cleveland Clinic evaluating 254 large colon polyps with high-grade dysplasia resected using ESD or EMR, Mehta et al13Mehta N. Abushahin A. Sadaps M. et al.Recurrence with malignancy after endoscopic resection of large colon polyps with high-grade dysplasia: incidence and risk factors.Surg Endosc. 2021; 35: 2500-2508Crossref PubMed Scopus (5) Google Scholar found that malignancy after resection occurred exclusively in patients who underwent p-EMR. Although the principal technique of both organ-sparing procedures, p-EMR and ESD, revolves around separation of a superficial (mucosal or submucosal) GI lesion from the deeper layers, in p-EMR, the electrosurgical separation of the anatomic planes occurs at once, which often leads to incomplete resection, mandating the need for additional interventions. Indeed, an array of additional “ablative” techniques must be applied to the site of larger lesions resected using p-EMR, ranging from snare tip electrocoagulation to argon plasma coagulation.8Adler J. Toy D. Anderson J.C. et al.Metachronous neoplasias arise in a higher proportion of colon segments from which large polyps were previously removed, and can be used to estimate incomplete resection of 10-20 mm colorectal polyps.Clin Gastroenterol Hepatol. 2019; 17: 2277-2284Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 9Klein A. Tate D.J. Jayasekeran V. et al.Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.Gastroenterology. 2019; 156: 604-613.e3Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar, 10Sidhu M. Shahidi N. Gupta S. et al.Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps.Gastroenterology. 2021; 161: 163-170.e3Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Thus, we must admit that p-EMR is an imperfect way to resect lesions, making it very hard for the endoscopists to ascertain R0, and it also complicates the life of the pathologist, who has to look at various disarranged “pieces of a puzzle” to ascertain an oncologic resection. Nobody could convince us so far that looking at many fragments of tissue is as efficient to ascertain complete resections as looking at 1 well-pinned resection specimen. In contrast, the tissue separation with ESD is gradual and stepwise, allowing for tissue planes to be slowly detached and contract during the entire resection process, allowing more often for higher en bloc removal. Indeed, intended curative en bloc resection (R0) is a basic surgical and oncologic principle, which we also aim for when performing traditional polypectomy. This objective is partially lost during p-EMR. However, potential arguments for keeping the status quo are that p-EMR may be less costly, may be associated with shorter procedure duration, and may result in fewer adverse events. A large meta-analysis reviewing 21 studies and 281,344 polyps found no significant difference in bleeding risk between the ESD and EMR, with higher rates of perforation for ESD. However, ESD was associated with higher rates of en bloc removal and complete resection and lower rates of lateral involvement and recurrence.14Lim X.C. Nistala K.R.Y. Ng C.H. et al.Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal polyps: a meta-analysis and meta-regression with single arm analysis.World J Gastroenterol. 2021; 27: 3925-3939Crossref PubMed Scopus (8) Google Scholar Based on these aspects, performing a prospective, comparative study is justified. This is further warranted by the fact that even ESD has margin positivity in some cases, as shown in this and retrospective registry studies.9Klein A. Tate D.J. Jayasekeran V. et al.Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.Gastroenterology. 2019; 156: 604-613.e3Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar Few studies have compared the efficacy, costs, and outcomes of ESD vs surgery. In a case-matched comparison of ESD vs laparoscopic colectomy, Gamaleldin et al15Gamaleldin M. Benlice C. Delaney C.P. et al.Management of the colorectal polyp referred for resection: a case-matched comparison of advanced endoscopic surgery and laparoscopic colectomy.Surgery. 2018; 163: 522-527Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar found that the mean operative time was similar and that more patients in the ESD group underwent surveillance colonoscopy compared with the laparoscopic colectomy group. However, adverse events were higher in the surgical group (21% vs 15%).15Gamaleldin M. Benlice C. Delaney C.P. et al.Management of the colorectal polyp referred for resection: a case-matched comparison of advanced endoscopic surgery and laparoscopic colectomy.Surgery. 2018; 163: 522-527Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Costs were 43% less in the ESD group, despite all of the patients undergoing the procedure in the operating room. This study has some deficits, including a retrospective design and an “advantage” of expert vs novice ESD laparoscopists.15Gamaleldin M. Benlice C. Delaney C.P. et al.Management of the colorectal polyp referred for resection: a case-matched comparison of advanced endoscopic surgery and laparoscopic colectomy.Surgery. 2018; 163: 522-527Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar However, it reminds us that laparoscopic colectomy is still performed for many patients that could benefit from an organ-preserving intervention such as ESD. What is blocking ESD from entering center stage clinical practice? The first reason is technical. Performing ESD requires special training and expertise.16Draganov P.V. Wang A.Y. Othman M.O. et al.AGA Institute Clinical Practice update: endoscopic submucosal dissection in the United States.Clin Gastroenterol Hepatol. 2019; 17: 16-25.e1Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar However, any advanced procedure in GI endoscopy requires special training, and this should not be an excuse to use less effective methods of resection. Also, now there are enough places in the United States performing ESD, allowing for learning this advanced endoscopic technique.16Draganov P.V. Wang A.Y. Othman M.O. et al.AGA Institute Clinical Practice update: endoscopic submucosal dissection in the United States.Clin Gastroenterol Hepatol. 2019; 17: 16-25.e1Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar Second, in the past, there were more adverse events when performing ESD. Since 1999, however, the rate of adverse events has drastically fallen, likely because of further technical refinements, innovation, and availability of endoscopic resection tools and submucosal injection substances.1Saito Y. Fujii T. Kondo H. et al.Endoscopic treatment for laterally spreading tumors in the colon.Endoscopy. 2001; 33: 682-686Crossref PubMed Scopus (144) Google Scholar,3Lee E.J. Lee J.B. Lee S.H. et al.Endoscopic submucosal dissection for colorectal tumors—1,000 colorectal ESD cases: one specialized institute’s experiences.Surg Endosc. 2013; 27: 31-39Crossref PubMed Scopus (120) Google Scholar,7Ohata K. Kobayashi N. Sakaj E. et al.Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan.Gastroenterology. 2022; 163: 1423-1434Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Third, there is still a generalized belief or trust among many endoscopists that p-EMR results in high R0 resection rates.17Lee E.Y. Bourke M.J. EMR should be the first-line treatment for large laterally spreading colorectal lesions.Gastrointest Endosc. 2016; 84: 326-328Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar But high-quality studies demonstrate that p-EMR still carries unacceptably high rates of incomplete resection.8Adler J. Toy D. Anderson J.C. et al.Metachronous neoplasias arise in a higher proportion of colon segments from which large polyps were previously removed, and can be used to estimate incomplete resection of 10-20 mm colorectal polyps.Clin Gastroenterol Hepatol. 2019; 17: 2277-2284Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 9Klein A. Tate D.J. Jayasekeran V. et al.Thermal ablation of mucosal defect margins reduces adenoma recurrence after colonic endoscopic mucosal resection.Gastroenterology. 2019; 156: 604-613.e3Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar, 10Sidhu M. Shahidi N. Gupta S. et al.Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps.Gastroenterology. 2021; 161: 163-170.e3Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 11Nakajima T. Sakamoto T. Hori S. et al.Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.Surg Endosc. 2022; 36: 515-525Crossref PubMed Scopus (3) Google Scholar, 12Oka S. Tanaka S. Saito Y. et al.Colorectal Endoscopic Resection Standardization Implementation Working Group of the Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan.Am J Gastroenterol. 2015; 110: 697-707Crossref PubMed Scopus (177) Google Scholar, 13Mehta N. Abushahin A. Sadaps M. et al.Recurrence with malignancy after endoscopic resection of large colon polyps with high-grade dysplasia: incidence and risk factors.Surg Endosc. 2021; 35: 2500-2508Crossref PubMed Scopus (5) Google Scholar Fourth, reimbursement issues may impede performing a procedure that takes more time. However, in October 2021, the Centers for Medicare and Medicaid Services expanded the reimbursement for ESD with the code C9779.18Centers for Medicare and Medicaid Services. CMS Manual System. Pub 100-04 Medicare Claims Processing. Table 6. New HCPCS Code Describing the Endoscopic submucosal dissection (ESD) procedure. Effective October 1, 2021. September 16, 2021. Available at: https://www.cms.gov/files/document/R10997CP.pdf#page=21. Accessed July 22, 2022.Google Scholar In Germany, the GI societies have also worked on proper coding and improved reimbursement for ESD and endoscopic full-thickness resection. In Japan, the issue of reimbursement was also addressed to reflect the true value of this procedure.19Saito Y. Nakajima T. Sakamoto T. et al.Clinical pathway to discharge three days after colorectal endoscopic submucosal dissection: for whom and for what purpose?.Dig Endosc. 2015; 27: 662-664Crossref PubMed Scopus (1) Google Scholar Finally, lack of expertise in a technique may antagonize supporting it. At the time when we were not performing ESD, we were hesitant to accept this technique.20Mönkemüller K. Neumann H. Malfertheiner P. et al.Advanced colon polypectomy.Clin Gastroenterol Hepatol. 2009; 7: 641-652Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar However, upon learning it, we clearly saw its benefits and advantages. ESD continues to evolve, now including lots of resection and hemostatic tools, combined snares, injection substances, and a multitude of traction devices. In summary, this study has shown that ESD is safe and efficient to resect large, advanced colonic neoplastic lesions, with low adverse events rates and excellent long-term outcomes. The mounting evidence appears to demonstrate that ESD is a superior technique in en bloc, curative oncologic resection, and long-term outcomes. Whereas p-EMR has not evolved much since its inception 50 years ago, ESD has continued to improve and gain acceptance among colonoscopists for patients with large colorectal lesions. Now that ESD is being performed more commonly in the West, a top priority is to validate its safety and efficacy in our own populations and using our own skills before definitely embracing it as the organ-sparing, minimally invasive endoscopic surgical procedure of choice for large colorectal polyps. Long-term Outcomes After Endoscopic Submucosal Dissection for Large Colorectal Epithelial Neoplasms: A Prospective, Multicenter, Cohort Trial From JapanGastroenterologyVol. 163Issue 5PreviewAccurate histologic assessment facilitated by endoscopic submucosal dissection enables stratification of the risk of lymph node metastasis and determines the necessity of additional surgery, which may have led to a good long-term prognosis. Full-Text PDF