Expert Review of Gastroenterology & Hepatology
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Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon Pavlos Z Kaimakliotis & Vinay Chandrasekhara To cite this article: Pavlos Z Kaimakliotis & Vinay Chandrasekhara (2014) Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon, Expert Review of Gastroenterology & Hepatology, 8:5, 521-531, DOI: 10.1586/17474124.2014.902305 To link to this article: http://dx.doi.org/10.1586/17474124.2014.902305
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Date: 12 December 2016, At: 18:29
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Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon Expert Rev. Gastroenterol. Hepatol. 8(5), 521–531 (2014)
Pavlos Z Kaimakliotis and Vinay Chandrasekhara* Gastroenterology Division, University of Pennsylvania Health System, Philadelphia, PA, USA *Author for correspondence: Tel.: +1 215 349 8356 [email protected]
Endoscopic mucosal resection (EMR) with curative intent has evolved into a safe and effective technique and is currently the gold standard for management of large colonic epithelial neoplasms. Piecemeal EMR is associated with a high risk of local recurrence requiring vigilant surveillance and repeat interventions. Endoscopic submucosal dissection (ESD) was introduced in Japan for the management of early gastric cancer, and has recently been described for en bloc resection of colonic lesions greater than 20 mm. En bloc resection allows accurate histological assessment of the depth of invasion, minimizes the risk of local recurrence and helps determine additional therapy. Morphologic classification of lesions prior to resection allows prediction of depth of invasion and risk of nodal metastasis, allowing selection of the appropriate intervention. This review provides an overview of the assessment of epithelial neoplasms of the colon and the application of EMR and ESD techniques in their management. KEYWORDS: colonic epithelial neoplasms • curative endoscopic resection • endoscopic morphologic classification of colonic epithelial neoplasms • endoscopic mucosal resection • endoscopic submucosal dissection
Colon cancer is the most common gastrointestinal malignancy in the USA and the second leading cause of cancer deaths among men and women. Colonoscopy and polypectomy are the cornerstone for the detection and prevention of colorectal cancer. Endoscopic mucosal resection (EMR) is fundamental in the armamentarium for management of advanced colonic neoplastic lesions and prevention of colorectal cancer. Refinement of EMR techniques and equipment over the past 40 years including submucosal injection, microprocessor controlled electrosurgical generators and closure devices have improved the safety profile of colonic EMR resulting in an efficient and cost-effective tool compared with the alternative, which is surgical resection. In Japan, endoscopic submucosal dissection (ESD) is routinely employed for the endoscopic management of early gastric cancers resulting in improved curative resections, higher rates of en bloc resection and better pathologic assessment of lateral and deep margins for lymphovascular invasion compared with EMR [1]. Case reports of ESD for colorectal epithelial informahealthcare.com
10.1586/17474124.2014.902305
neoplasms were first described in Japan for en bloc resection of rectal lesions by direct dissection along the submucosal layer [2]. Colonic polyps >20 mm are typically removed in piecemeal fashion employing EMR techniques, whereas, the advantage of ESD is that similar lesions can be removed en bloc. Evaluation of lesions for resection
The majority of polyps detected at colonoscopy are 10 mm in size, presence of high-grade dysplasia, adenomas with villous features or sessile serrated adenomas with any dysplasia. The prevalence of advanced adenomas in patients undergoing screening colonoscopy is 5.7% based on a recent metaanalysis [3]. Since the introduction of submucosal injection of sessile polyps by Deyhle in 1973, endoscopists have been able to safely and effectively resect sessile polyps >20 mm [4].
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Protruding
Non-protruding
Excavated
endoscopist to estimate the depth of invasion, and therefore, the likely risk of lymph node metastases. Morphologic features & malignant potential
Flat elevation (0-IIa)
Paris classification & Kudo pit pattern Pedunculated (0-Ip)
Sessile (0-Is)
Completely flat (0-IIb)
Excavated (0-III)
Slightly depressed (0-IIc)
Figure 1. Paris classification schematic representation of mucosal neoplasia. Protruding lesions include pedunculated (0–Ip) and sessile (0–Is). Non-protruding lesions include flat elevated lesions (0–IIa), lesions with flat mucosal change (0–IIb) and slightly depressed lesions (0–IIc). An ulcer is seen with excavated lesions (0–III). Adapted with permission from [69].
It is important to carefully characterize epithelial tumors at the time of endoscopy prior to proceeding with a therapeutic intervention with curative intent. Lesions with a low risk of nodal metastases can be successfully treated with endoscopic therapy. The incidence of nodal metastases in advanced neoplastic lesions of the colon increases with the depth of invasion into the submucosa. The risk of nodal metastases with submucosal invasion (SMI) limited to 1000 mm (SM1) is less than 1%, whereas lymph node metastases increases significantly with invasion into the submucosal beyond 1000 mm, 6% for SM2 and 14% for SM3 invasion [5]. The preprocedural assessment is primarily based on the morphologic features of the lesion, which allows the
Large sessile polyps of the colon comprise either tubular adenomas or sessile serrated adenomas. Further characterization based on the Paris classification helps predict risk of SMI (FIGURE 1) [6]. Neoplastic lesions that protrude more than twice the thickness of adjacent mucosa are classified as type 0–I lesions. Nonprotruding lesions may be slightly elevated (0–IIa), completely flat (0–IIb) or slightly depressed (0–IIc) and comprise 50% of neoplastic lesions. The majority (44%) being 0–IIa lesions, 5% 0–IIc and 0–IIb lesions being rare [5]. Non-protruding elevated lesions (0–IIa) with diameter extending beyond 20 mm have also been termed ‘laterally spreading’ lesions. Lesions may have mixed morphologic features such as a flat elevated lesion with a depressed component (0–IIa + c) (FIGURE 2). Type III lesions are excavated and are rare [5,6]. The frequency of SMI is highest for sessile protruding (0–Is) lesions (34%) and non-protruding depressed (0–IIc) lesions (61%). For protruding pedunculated (0–Ip), non-protruding elevated (0–IIa) and completely flat (0–IIb) lesions, the risk was the lowest at 4 and 0%, respectively. The Kudo classification characterizes lesions according to surface pit patterns (type I–V) using magnifying endoscopy with a correlation between lesion type and pit pattern. Type I consist of round regular pits found in normal mucosa and type II consists of stellar or papillary pits, which are found in hyperplastic polyps. Type III (IIIL and IIIs) are tubular or roundish pit patterns and correspond to adenomas. Type IV are dendritic or gyrus-like pits and are primarily seen in adenomas, but also found in some carcinomas. Type V irregular and non-structural pit patterns are primarily found in carcinomas and are associated with deep submucosal SM2 and SM3 invasion and higher lymph node metastases (10–15%) [7,8]. Paris classification 0–IIa + c morphology, non-granular surface and Kudo pit pattern type V are recognized as predictors of SMI (FIGURE 3) [9]. Narrow-band imaging International Colorectal Endoscopic classification
Figure 2. Lesion with Paris classification 0-IIa + c. Histopathology showed sessile serrated adenoma after complete endoscopic resection.
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Narrow-band imaging (NBI) is an optical image enhancement technology that optimizes hemoglobin light absorption to better characterize mucosal and submucosal vessel patterns. The NBI International Colorectal Endoscopic (NICE) classification without optical magnification was recently developed and validated to allow endoscopic prediction of colorectal polyp histology and differentiation between hyperplastic (type 1) and adenomatous (type 2) colorectal polyps (FIGURE 4) [10]. Hewett et al. showed that during real time, colonoscopy endoscopists made diagnoses with high confidence for 75% of consecutive small colorectal polyps, with 89% accuracy, 98% sensitivity and 95% negative predictive values. A limitation of the NICE classification is that it does not specifically incorporate sessile serrated adenomas into the classification. Expert Rev. Gastroenterol. Hepatol. 8(5), (2014)
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The NICE classification was further expanded to differentiate deep SMI (‡1000 mm) (type 3) from adenomas or lesions with superficial SMI (20 mm consist of 0.8–5.2% of all polyps found in various series [17–19]. Flat or sessile lesions >15–20 mm should be removed using EMR technique and polyps >20 mm typically require piecemeal resection. The evolution of ESD techniques and expertise allows higher rates of en bloc resections of colonic epithelial neoplastic lesions >20 mm in size. Size alone though does not predict resectability of colonic polyps. Factors that also affect resectability include the luminal circumference and length of the polyp. A polyp that extends beyond 30% of the lumen circumference or beyond two haustral folds poses further technical difficulty, though not impossible to resect depending on expertise. Polyp location behind a fold or at a flexure may render it inaccessible for safe and effective endoscopic resection. Lesions involving the appendiceal orifice or the ileocecal valve may be amenable to endoscopic resection, if the margins of the lesion can be clearly delineated B
Size, circumference and location
Size has a significant impact on whether a polyp can be resected endoscopically. Large polyps are >20 mm and giant polyps are >30 mm. Flat or sessile polyps 10% [49]. Intraprocedural bleeding can be controlled by various techniques including injection of epinephrine, APC, coagulation graspers, endoscopic application of clips. A recent study by Fahrtash-Bahin et al. describes the use of soft coagulation applied using the tip of the snare to control intraprocedural bleeding [53]. Snare tip soft coagulation was successful in controlling intraprocedural bleeding in 91% of cases with no related adverse events and no difference in postprocedural adverse events, including no perforations, compared with patients with no intraprocedural bleeding, making this technique efficient, effective and safe. Delayed bleeding is one of the most common complications of EMR, typically occurring in less than 10% of cases and typically managed with a combination of endoscopic clips and epinephrine injection [54,55]. Application of thermal treatment at the polypectomy site is avoided to prevent transmural injury. Bleeding may occur as late as 12 days after the procedure with the majority of cases occurring in the first 48 h. A retrospective review of 249 patients with attempt at EMR reported a delayed bleeding rate of 7.2%, double of that noted with intraprocedural bleeding [49]. A third of those patients with delayed bleeding did not require hospitalization and had spontaneous cessation of bleeding. Of the hospitalized patients, 28% required a second colonoscopy, the majority of which underwent endoscopic intervention with a combination of clips and/ or epinephrine injection. All cases of delayed bleeding were observed between 24 h and 6 days after the initial EMR. There is no significant association between delayed bleeding and polyp size. Prior studies have identified risk factors for delayed bleeding, which include right-sided lesions, advanced patient age and recent aspirin or anticoagulation use [56,57]. Some endoscopists advocate the discontinuation of aspirin 5– 7 days prior to colonic EMR [55]. The use of APC has not been shown to decrease the risk of delayed postpolypectomy bleeding and in one study, the use of APC was associated with higher rates of delayed bleeding [49,58]. Our own practice is to adhere to the American Society for Gastrointestinal Endoscopy guidelines regarding management of antiplatelet agents and anticoagulation [59]. Contraindications to EMR & referral for surgery
Initial assessment of a lesion to determine resectability is performed before undertaking EMR, taking into account the accessibility of the polyp with respect to location and position. Other features that should alert the endoscopist to a potentially unresectable lesion include submucosal scarring and fixation due to prior intervention or deep submucosal tumor invasion. Moss et al. identified Paris classification 0–IIa + c morphology, non-granular surface and Kudo pit pattern V as risk factors for SMI in colonic polyps in patients referred for endoscopic management [9]. In the same study, risk factors for lack of efficacy included attempt at prior resection and involvement of the informahealthcare.com
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ileocecal valve, and risk factors for recurrence after EMR were lesion size >40 mm and use of APC. Surveillance & recurrence
Timing of follow-up after EMR usually depends on the histopathology of the resected lesion and the endoscopist’s assessment of complete resection. The resection site should be carefully examined. Residual adenoma can be treated with simple polypectomy or repeat EMR, though submucosal scarring may result in an ineffective lift, requiring the use of alternative ablation techniques to destroy residual neoplastic tissue. After documenting complete eradication, repeat endoscopy is performed at 1 year, followed by the recommended surveillance program. The recurrence of neoplasia after EMR of referred polyps may be as high as 55% in some studies, reflecting the challenging nature of these lesions and the need for close endoscopic surveillance [23,60–62]. The Australian Colonic Endoscopic resection study group conducted a prospective, multicenter, observational study of all patients referred for EMR of sessile colorectal polyps 20 mm or greater in size and showed that EMR was effective in complete resection of the polyp in a single session in 89.2% of patients, with a recurrence of 20% [9]. Endoscopic submucosal dissection
Unlike EMR, ESD is not yet recognized as an established technique for management of early colorectal epithelial neoplasia, primarily due to its technical difficulty. However, there have been significant advances in technique, equipment and experience. Given the complexity of ESD, performance of this technique requires not only great experience in performing colonoscopy, but also familiarity with the various available equipment and electrosurgical settings and effects. In a study by Tanaka et al., two endoscopists with prior experience in performing over 100 gastric ESDs performed ESD on 70 colorectal lesions >20 mm [63]. The average time required for ESD was 70.5 min (15–180 min), and the histologic rate of complete en bloc resection was 80%. Perforation occurred in 10% of cases and bleeding in 1.4% of cases. Rates of perforation appeared to decrease with increase in endoscopist experience with colorectal ESD. Performance of colonic ESD requires prior experience in performing ESD in the stomach and rectum, which is safer due to lower risk of perforation. Prior experience in performing ESD in animal models is also beneficial. The challenge with performing ESD in the colon arises from the thin wall of the colon resulting in higher rates of perforation compared with gastric ESD and also EMR of colonic lesions. With colonic perforation, there is also the risk of fecal contamination and peritonitis that is more likely to require surgical intervention compared with perforation in the upper GI tract. There have been attempts to standardize the indications for performing ESD on colorectal lesions by the Colorectal ESD Standardization Implementation Working Group [63–65]. These suggested indications for colorectal ESD include resection of lesions that would otherwise be difficult to remove en bloc by 527
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EMR and particularly laterally spreading non-granular lesions >20 mm or lesions with a type V pit pattern with high suspicion for early adenocarcinoma for attempt at en bloc resection. Other indications for ESD are lesions with suspected fibrosis from prior intervention or peristalsis, sporadic localized lesions in the background of inflammation secondary to inflammatory bowel disease and localized residual epithelial neoplasia after EMR. If ESD expertise is not available, the lesion should be biopsied and the area tattooed if necessary, and the patient should be referred for laparoscopic resection. In the past decade, various needle knifes have been made available that have allowed ESD to be technically more feasible and safer to perform. The use of CO2 insufflation has also contributed to the increased safety in performing longer procedures with less intra- and postprocedural discomfort and complications [66]. The use of microprocessor controlled ESUs with various highfrequency cutting and coagulating current modes is essential for effective and safe performance of the various stages of ESD. Nishiyama et al. reported outcomes from a cohort of 282 patients with colorectal lesions >20 mm (median 25 mm, range 6–75 mm), which underwent attempt at ESD, with 50.3% of lesions located in the proximal colon [67]. En bloc resection was achieved in 89.2% of lesions and complete histologic resection was achieved in 79.1%. There was no recurrence or residual disease associated with complete resection at followup. Right-sided location significantly contributed incomplete resection. Perforation was observed in 8.1% of cases, the majority of which occurred during or immediately after ESD and were treated with endoscopic clip closure and conservative medical management. Patients presenting with delayed perforation (8.3% of all perforations) occurred 24 h after ESD and required surgical intervention. A recent review of ESD outcomes data from 13 institutions in Japan including 2719 cases of colorectal ESD showed an endoscopic en bloc resection rate of 82.8% (range 61–98.2%), a histologic en bloc resection of 75.7% (58–95.5%) [68]. Complications included perforation at a rate of 4.7% (1.4–8.2%) and bleeding at a rate of 1.5% (0.5–9.5%). Local recurrence was 1.2% (0–11%). Expert commentary
The choice of endotherapy technique depends on a variety of factors. The primary limitation of EMR is the inability to resect lesions >20 mm en bloc. Piecemeal EMR is associated with a high risk of local recurrence compared with en bloc
resection, especially for lesions >40 mm [9]. The risk of invasive recurrence should also be taken into account when performing EMR for large laterally spreading lesions [1]. Persistent surveillance and effective management of recurrent neoplastic tissue does allow for eventual complete resection with EMR with a favorable safety profile. Despite the potential in achieving high rates of en bloc resection of large colorectal polyps, initial studies of colorectal ESD show high rates of perforation [68]. Given the technical complexity and steep learning curve associated with performing ESD, coupled with the current lack of standardized formal training in the West, EMR remains the standard of care for management of large, laterally spreading colorectal epithelial neoplasms without obvious SMI. The incorporation of the Paris morphological classification and the Kudo pit pattern in the assessment of large colonic lesions will offer endoscopists additional tools to determine and deliver the appropriate therapeutic intervention. EMR is a safe, effective and efficient method for the management of colorectal epithelial neoplasia when performed by experienced endoscopists. Standardization of ESD techniques, equipment and training in the next few years will offer endoscopists further options for the management of neoplastic lesions of the colon. Five-year view
The next 5 years will see more data emerge on the outcomes of large studies on ESD of colonic epithelial neoplasms, mainly out of centers with large experience in gastric ESD. Experience with colonic ESD will continue to grow, especially as training to perform ESD becomes standardized. Equipment for ESD such as electrosurgical knives will continue to develop and will further contribute to decreasing procedural time and fewer complications. The development of novel closure devices will allow for more effective management of complications such as perforation. These advancements will further shape the role of ESD in conjunction with EMR in the management of large epithelial neoplasms of the colon. Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.
Key issues • Morphological assessment of epithelial neoplasms of the colon allows for prediction of lesions at high risk for submucosal invasion. • Endoscopic mucosal resection (EMR) is the gold standard for management of large epithelial neoplasms of the colon. • In expert hands, EMR has a high success rate for complete resection of epithelial neoplasms of the colon. EMR has a high rate of local recurrence, which can be effectively managed with repeat EMR and ablation. • Endoscopic submucosal dissection (ESD) is a promising, evolving technique for the management of large epithelial neoplasms of the colon with high rates of en bloc resection. However, ESD is technically challenging and associated with a high rate of perforation. • The role of ESD in the management of epithelial neoplasms of the colon remains to be defined.
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colorectal lesions: clinical implications and subtype analysis of the Kudo type V pit pattern using high-magnification-chromoscopic colonoscopy. Colorectal Dis 2004;6(5): 369-75
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ISSN: 1747-4124 (Print) 1747-4132 (Online) Journal homepage: http://www.tandfonline.com/loi/ierh20
Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon Pavlos Z Kaimakliotis & Vinay Chandrasekhara To cite this article: Pavlos Z Kaimakliotis & Vinay Chandrasekhara (2014) Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon, Expert Review of Gastroenterology & Hepatology, 8:5, 521-531, DOI: 10.1586/17474124.2014.902305 To link to this article: http://dx.doi.org/10.1586/17474124.2014.902305
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Date: 12 December 2016, At: 18:29
Review
Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial neoplasia of the colon Expert Rev. Gastroenterol. Hepatol. 8(5), 521–531 (2014)
Pavlos Z Kaimakliotis and Vinay Chandrasekhara* Gastroenterology Division, University of Pennsylvania Health System, Philadelphia, PA, USA *Author for correspondence: Tel.: +1 215 349 8356 [email protected]
Endoscopic mucosal resection (EMR) with curative intent has evolved into a safe and effective technique and is currently the gold standard for management of large colonic epithelial neoplasms. Piecemeal EMR is associated with a high risk of local recurrence requiring vigilant surveillance and repeat interventions. Endoscopic submucosal dissection (ESD) was introduced in Japan for the management of early gastric cancer, and has recently been described for en bloc resection of colonic lesions greater than 20 mm. En bloc resection allows accurate histological assessment of the depth of invasion, minimizes the risk of local recurrence and helps determine additional therapy. Morphologic classification of lesions prior to resection allows prediction of depth of invasion and risk of nodal metastasis, allowing selection of the appropriate intervention. This review provides an overview of the assessment of epithelial neoplasms of the colon and the application of EMR and ESD techniques in their management. KEYWORDS: colonic epithelial neoplasms • curative endoscopic resection • endoscopic morphologic classification of colonic epithelial neoplasms • endoscopic mucosal resection • endoscopic submucosal dissection
Colon cancer is the most common gastrointestinal malignancy in the USA and the second leading cause of cancer deaths among men and women. Colonoscopy and polypectomy are the cornerstone for the detection and prevention of colorectal cancer. Endoscopic mucosal resection (EMR) is fundamental in the armamentarium for management of advanced colonic neoplastic lesions and prevention of colorectal cancer. Refinement of EMR techniques and equipment over the past 40 years including submucosal injection, microprocessor controlled electrosurgical generators and closure devices have improved the safety profile of colonic EMR resulting in an efficient and cost-effective tool compared with the alternative, which is surgical resection. In Japan, endoscopic submucosal dissection (ESD) is routinely employed for the endoscopic management of early gastric cancers resulting in improved curative resections, higher rates of en bloc resection and better pathologic assessment of lateral and deep margins for lymphovascular invasion compared with EMR [1]. Case reports of ESD for colorectal epithelial informahealthcare.com
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neoplasms were first described in Japan for en bloc resection of rectal lesions by direct dissection along the submucosal layer [2]. Colonic polyps >20 mm are typically removed in piecemeal fashion employing EMR techniques, whereas, the advantage of ESD is that similar lesions can be removed en bloc. Evaluation of lesions for resection
The majority of polyps detected at colonoscopy are 10 mm in size, presence of high-grade dysplasia, adenomas with villous features or sessile serrated adenomas with any dysplasia. The prevalence of advanced adenomas in patients undergoing screening colonoscopy is 5.7% based on a recent metaanalysis [3]. Since the introduction of submucosal injection of sessile polyps by Deyhle in 1973, endoscopists have been able to safely and effectively resect sessile polyps >20 mm [4].
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Protruding
Non-protruding
Excavated
endoscopist to estimate the depth of invasion, and therefore, the likely risk of lymph node metastases. Morphologic features & malignant potential
Flat elevation (0-IIa)
Paris classification & Kudo pit pattern Pedunculated (0-Ip)
Sessile (0-Is)
Completely flat (0-IIb)
Excavated (0-III)
Slightly depressed (0-IIc)
Figure 1. Paris classification schematic representation of mucosal neoplasia. Protruding lesions include pedunculated (0–Ip) and sessile (0–Is). Non-protruding lesions include flat elevated lesions (0–IIa), lesions with flat mucosal change (0–IIb) and slightly depressed lesions (0–IIc). An ulcer is seen with excavated lesions (0–III). Adapted with permission from [69].
It is important to carefully characterize epithelial tumors at the time of endoscopy prior to proceeding with a therapeutic intervention with curative intent. Lesions with a low risk of nodal metastases can be successfully treated with endoscopic therapy. The incidence of nodal metastases in advanced neoplastic lesions of the colon increases with the depth of invasion into the submucosa. The risk of nodal metastases with submucosal invasion (SMI) limited to 1000 mm (SM1) is less than 1%, whereas lymph node metastases increases significantly with invasion into the submucosal beyond 1000 mm, 6% for SM2 and 14% for SM3 invasion [5]. The preprocedural assessment is primarily based on the morphologic features of the lesion, which allows the
Large sessile polyps of the colon comprise either tubular adenomas or sessile serrated adenomas. Further characterization based on the Paris classification helps predict risk of SMI (FIGURE 1) [6]. Neoplastic lesions that protrude more than twice the thickness of adjacent mucosa are classified as type 0–I lesions. Nonprotruding lesions may be slightly elevated (0–IIa), completely flat (0–IIb) or slightly depressed (0–IIc) and comprise 50% of neoplastic lesions. The majority (44%) being 0–IIa lesions, 5% 0–IIc and 0–IIb lesions being rare [5]. Non-protruding elevated lesions (0–IIa) with diameter extending beyond 20 mm have also been termed ‘laterally spreading’ lesions. Lesions may have mixed morphologic features such as a flat elevated lesion with a depressed component (0–IIa + c) (FIGURE 2). Type III lesions are excavated and are rare [5,6]. The frequency of SMI is highest for sessile protruding (0–Is) lesions (34%) and non-protruding depressed (0–IIc) lesions (61%). For protruding pedunculated (0–Ip), non-protruding elevated (0–IIa) and completely flat (0–IIb) lesions, the risk was the lowest at 4 and 0%, respectively. The Kudo classification characterizes lesions according to surface pit patterns (type I–V) using magnifying endoscopy with a correlation between lesion type and pit pattern. Type I consist of round regular pits found in normal mucosa and type II consists of stellar or papillary pits, which are found in hyperplastic polyps. Type III (IIIL and IIIs) are tubular or roundish pit patterns and correspond to adenomas. Type IV are dendritic or gyrus-like pits and are primarily seen in adenomas, but also found in some carcinomas. Type V irregular and non-structural pit patterns are primarily found in carcinomas and are associated with deep submucosal SM2 and SM3 invasion and higher lymph node metastases (10–15%) [7,8]. Paris classification 0–IIa + c morphology, non-granular surface and Kudo pit pattern type V are recognized as predictors of SMI (FIGURE 3) [9]. Narrow-band imaging International Colorectal Endoscopic classification
Figure 2. Lesion with Paris classification 0-IIa + c. Histopathology showed sessile serrated adenoma after complete endoscopic resection.
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Narrow-band imaging (NBI) is an optical image enhancement technology that optimizes hemoglobin light absorption to better characterize mucosal and submucosal vessel patterns. The NBI International Colorectal Endoscopic (NICE) classification without optical magnification was recently developed and validated to allow endoscopic prediction of colorectal polyp histology and differentiation between hyperplastic (type 1) and adenomatous (type 2) colorectal polyps (FIGURE 4) [10]. Hewett et al. showed that during real time, colonoscopy endoscopists made diagnoses with high confidence for 75% of consecutive small colorectal polyps, with 89% accuracy, 98% sensitivity and 95% negative predictive values. A limitation of the NICE classification is that it does not specifically incorporate sessile serrated adenomas into the classification. Expert Rev. Gastroenterol. Hepatol. 8(5), (2014)
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The NICE classification was further expanded to differentiate deep SMI (‡1000 mm) (type 3) from adenomas or lesions with superficial SMI (20 mm consist of 0.8–5.2% of all polyps found in various series [17–19]. Flat or sessile lesions >15–20 mm should be removed using EMR technique and polyps >20 mm typically require piecemeal resection. The evolution of ESD techniques and expertise allows higher rates of en bloc resections of colonic epithelial neoplastic lesions >20 mm in size. Size alone though does not predict resectability of colonic polyps. Factors that also affect resectability include the luminal circumference and length of the polyp. A polyp that extends beyond 30% of the lumen circumference or beyond two haustral folds poses further technical difficulty, though not impossible to resect depending on expertise. Polyp location behind a fold or at a flexure may render it inaccessible for safe and effective endoscopic resection. Lesions involving the appendiceal orifice or the ileocecal valve may be amenable to endoscopic resection, if the margins of the lesion can be clearly delineated B
Size, circumference and location
Size has a significant impact on whether a polyp can be resected endoscopically. Large polyps are >20 mm and giant polyps are >30 mm. Flat or sessile polyps 10% [49]. Intraprocedural bleeding can be controlled by various techniques including injection of epinephrine, APC, coagulation graspers, endoscopic application of clips. A recent study by Fahrtash-Bahin et al. describes the use of soft coagulation applied using the tip of the snare to control intraprocedural bleeding [53]. Snare tip soft coagulation was successful in controlling intraprocedural bleeding in 91% of cases with no related adverse events and no difference in postprocedural adverse events, including no perforations, compared with patients with no intraprocedural bleeding, making this technique efficient, effective and safe. Delayed bleeding is one of the most common complications of EMR, typically occurring in less than 10% of cases and typically managed with a combination of endoscopic clips and epinephrine injection [54,55]. Application of thermal treatment at the polypectomy site is avoided to prevent transmural injury. Bleeding may occur as late as 12 days after the procedure with the majority of cases occurring in the first 48 h. A retrospective review of 249 patients with attempt at EMR reported a delayed bleeding rate of 7.2%, double of that noted with intraprocedural bleeding [49]. A third of those patients with delayed bleeding did not require hospitalization and had spontaneous cessation of bleeding. Of the hospitalized patients, 28% required a second colonoscopy, the majority of which underwent endoscopic intervention with a combination of clips and/ or epinephrine injection. All cases of delayed bleeding were observed between 24 h and 6 days after the initial EMR. There is no significant association between delayed bleeding and polyp size. Prior studies have identified risk factors for delayed bleeding, which include right-sided lesions, advanced patient age and recent aspirin or anticoagulation use [56,57]. Some endoscopists advocate the discontinuation of aspirin 5– 7 days prior to colonic EMR [55]. The use of APC has not been shown to decrease the risk of delayed postpolypectomy bleeding and in one study, the use of APC was associated with higher rates of delayed bleeding [49,58]. Our own practice is to adhere to the American Society for Gastrointestinal Endoscopy guidelines regarding management of antiplatelet agents and anticoagulation [59]. Contraindications to EMR & referral for surgery
Initial assessment of a lesion to determine resectability is performed before undertaking EMR, taking into account the accessibility of the polyp with respect to location and position. Other features that should alert the endoscopist to a potentially unresectable lesion include submucosal scarring and fixation due to prior intervention or deep submucosal tumor invasion. Moss et al. identified Paris classification 0–IIa + c morphology, non-granular surface and Kudo pit pattern V as risk factors for SMI in colonic polyps in patients referred for endoscopic management [9]. In the same study, risk factors for lack of efficacy included attempt at prior resection and involvement of the informahealthcare.com
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ileocecal valve, and risk factors for recurrence after EMR were lesion size >40 mm and use of APC. Surveillance & recurrence
Timing of follow-up after EMR usually depends on the histopathology of the resected lesion and the endoscopist’s assessment of complete resection. The resection site should be carefully examined. Residual adenoma can be treated with simple polypectomy or repeat EMR, though submucosal scarring may result in an ineffective lift, requiring the use of alternative ablation techniques to destroy residual neoplastic tissue. After documenting complete eradication, repeat endoscopy is performed at 1 year, followed by the recommended surveillance program. The recurrence of neoplasia after EMR of referred polyps may be as high as 55% in some studies, reflecting the challenging nature of these lesions and the need for close endoscopic surveillance [23,60–62]. The Australian Colonic Endoscopic resection study group conducted a prospective, multicenter, observational study of all patients referred for EMR of sessile colorectal polyps 20 mm or greater in size and showed that EMR was effective in complete resection of the polyp in a single session in 89.2% of patients, with a recurrence of 20% [9]. Endoscopic submucosal dissection
Unlike EMR, ESD is not yet recognized as an established technique for management of early colorectal epithelial neoplasia, primarily due to its technical difficulty. However, there have been significant advances in technique, equipment and experience. Given the complexity of ESD, performance of this technique requires not only great experience in performing colonoscopy, but also familiarity with the various available equipment and electrosurgical settings and effects. In a study by Tanaka et al., two endoscopists with prior experience in performing over 100 gastric ESDs performed ESD on 70 colorectal lesions >20 mm [63]. The average time required for ESD was 70.5 min (15–180 min), and the histologic rate of complete en bloc resection was 80%. Perforation occurred in 10% of cases and bleeding in 1.4% of cases. Rates of perforation appeared to decrease with increase in endoscopist experience with colorectal ESD. Performance of colonic ESD requires prior experience in performing ESD in the stomach and rectum, which is safer due to lower risk of perforation. Prior experience in performing ESD in animal models is also beneficial. The challenge with performing ESD in the colon arises from the thin wall of the colon resulting in higher rates of perforation compared with gastric ESD and also EMR of colonic lesions. With colonic perforation, there is also the risk of fecal contamination and peritonitis that is more likely to require surgical intervention compared with perforation in the upper GI tract. There have been attempts to standardize the indications for performing ESD on colorectal lesions by the Colorectal ESD Standardization Implementation Working Group [63–65]. These suggested indications for colorectal ESD include resection of lesions that would otherwise be difficult to remove en bloc by 527
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EMR and particularly laterally spreading non-granular lesions >20 mm or lesions with a type V pit pattern with high suspicion for early adenocarcinoma for attempt at en bloc resection. Other indications for ESD are lesions with suspected fibrosis from prior intervention or peristalsis, sporadic localized lesions in the background of inflammation secondary to inflammatory bowel disease and localized residual epithelial neoplasia after EMR. If ESD expertise is not available, the lesion should be biopsied and the area tattooed if necessary, and the patient should be referred for laparoscopic resection. In the past decade, various needle knifes have been made available that have allowed ESD to be technically more feasible and safer to perform. The use of CO2 insufflation has also contributed to the increased safety in performing longer procedures with less intra- and postprocedural discomfort and complications [66]. The use of microprocessor controlled ESUs with various highfrequency cutting and coagulating current modes is essential for effective and safe performance of the various stages of ESD. Nishiyama et al. reported outcomes from a cohort of 282 patients with colorectal lesions >20 mm (median 25 mm, range 6–75 mm), which underwent attempt at ESD, with 50.3% of lesions located in the proximal colon [67]. En bloc resection was achieved in 89.2% of lesions and complete histologic resection was achieved in 79.1%. There was no recurrence or residual disease associated with complete resection at followup. Right-sided location significantly contributed incomplete resection. Perforation was observed in 8.1% of cases, the majority of which occurred during or immediately after ESD and were treated with endoscopic clip closure and conservative medical management. Patients presenting with delayed perforation (8.3% of all perforations) occurred 24 h after ESD and required surgical intervention. A recent review of ESD outcomes data from 13 institutions in Japan including 2719 cases of colorectal ESD showed an endoscopic en bloc resection rate of 82.8% (range 61–98.2%), a histologic en bloc resection of 75.7% (58–95.5%) [68]. Complications included perforation at a rate of 4.7% (1.4–8.2%) and bleeding at a rate of 1.5% (0.5–9.5%). Local recurrence was 1.2% (0–11%). Expert commentary
The choice of endotherapy technique depends on a variety of factors. The primary limitation of EMR is the inability to resect lesions >20 mm en bloc. Piecemeal EMR is associated with a high risk of local recurrence compared with en bloc
resection, especially for lesions >40 mm [9]. The risk of invasive recurrence should also be taken into account when performing EMR for large laterally spreading lesions [1]. Persistent surveillance and effective management of recurrent neoplastic tissue does allow for eventual complete resection with EMR with a favorable safety profile. Despite the potential in achieving high rates of en bloc resection of large colorectal polyps, initial studies of colorectal ESD show high rates of perforation [68]. Given the technical complexity and steep learning curve associated with performing ESD, coupled with the current lack of standardized formal training in the West, EMR remains the standard of care for management of large, laterally spreading colorectal epithelial neoplasms without obvious SMI. The incorporation of the Paris morphological classification and the Kudo pit pattern in the assessment of large colonic lesions will offer endoscopists additional tools to determine and deliver the appropriate therapeutic intervention. EMR is a safe, effective and efficient method for the management of colorectal epithelial neoplasia when performed by experienced endoscopists. Standardization of ESD techniques, equipment and training in the next few years will offer endoscopists further options for the management of neoplastic lesions of the colon. Five-year view
The next 5 years will see more data emerge on the outcomes of large studies on ESD of colonic epithelial neoplasms, mainly out of centers with large experience in gastric ESD. Experience with colonic ESD will continue to grow, especially as training to perform ESD becomes standardized. Equipment for ESD such as electrosurgical knives will continue to develop and will further contribute to decreasing procedural time and fewer complications. The development of novel closure devices will allow for more effective management of complications such as perforation. These advancements will further shape the role of ESD in conjunction with EMR in the management of large epithelial neoplasms of the colon. Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.
Key issues • Morphological assessment of epithelial neoplasms of the colon allows for prediction of lesions at high risk for submucosal invasion. • Endoscopic mucosal resection (EMR) is the gold standard for management of large epithelial neoplasms of the colon. • In expert hands, EMR has a high success rate for complete resection of epithelial neoplasms of the colon. EMR has a high rate of local recurrence, which can be effectively managed with repeat EMR and ablation. • Endoscopic submucosal dissection (ESD) is a promising, evolving technique for the management of large epithelial neoplasms of the colon with high rates of en bloc resection. However, ESD is technically challenging and associated with a high rate of perforation. • The role of ESD in the management of epithelial neoplasms of the colon remains to be defined.
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colorectal lesions: clinical implications and subtype analysis of the Kudo type V pit pattern using high-magnification-chromoscopic colonoscopy. Colorectal Dis 2004;6(5): 369-75
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