Federico Iacopini, MD
Endoscopic mucosal resection (EMR) permits the safe and easy removal of most small adenomas and early cancers in the gastrointestinal (GI) tract, but sometimes it is not reliable to ensure complete curative resection and associated with local recurrence. Endoscopic submucosal dissection (ESD) was developed to overcome these limitations, has shown advantages for the removal of difficult lesions, enhanced potential for curative resection, although it is significantly more technically challenging. As such, ESD is a standard in Japan and other East Asian countries, whereas EMR remains the approach of choice in the West.
Endoscopic Mucosal Resection Training
EMR and polypectomy are simple, effective, and safe procedures performed routinely by most endoscopists. However, outcomes are largely variable and severe adverse events do occur. Pohl et al1 showed that the rate of incomplete resection increases with the size of the lesion and ranges from 7% to 23% among endoscopists. Such observation has been confirmed by Duloy and colleagues2 in a recent prospective study including 13 high-volume screening colonoscopists in which competency in polypectomy was assessed using the Directly Observed Polypectomy Skills tool (DOPyS).3 Competence varied from 30% to 90% and was significantly lower for polyps 6 to 15 mm in size compared with those < 5 mm (50% vs 70%, P = .03). The authors also showed that specific skills for polypectomy were insufficient: An optimal position for polypectomy and a stable position of the endoscope were achieved in 61% and 58% of cases, respectively; the polypectomy site was studied for remnant tissue in 57%; snare size and placement were correct in 73%; and an appropriate amount of adjacent normal mucosa was resected in 50%. Finally, polypectomy competency was found not to correlate with diagnostic competence, thereby indicating that high-quality adenoma “detectors” are not necessarily high-quality adenoma “removers.”
The identification of indicators of difficulty is of the utmost importance and adverse events are indirect measures. Australian experts demonstrated that deep muscular injuries during EMR that result in perforation were associated with the location in the transverse colon (odds ratio [OR] 3.6), en bloc resection (OR 3.8), and high-grade dysplasia or submucosal (SM) invasive cancer (OR 3.0),4 whereas clinically relevant delayed bleedings were associated with a lesion size > 30 mm (OR 2.5), and the location in the proximal colon (OR 2.3).5 Similarly, Rutter et al6 in a large observational study showed that prognostics of delayed bleeding and perforation were location (cecum: OR 2.4 and OR 4.5, respectively) and size > 20 mm (OR 3.6 and OR 2.1, respectively). Difficulty prognostics were combined by Gupta and colleagues7 in an easy classification system called SMSA based on Size (difficulty increases with 1 cm increases), Morphology (sessile and flat are more difficult than pedunculated lesions), Site (right is more difficult than left colon), and Access (difficult vs easy). The SMSA score has been further validated by Longcroft-Wheaton et al,8 who concluded that it provides valuable information on success and risks of endoscopic resection. The European Society of Gastrointestinal Endoscopy recommends its use in clinical practice to stratify EMR difficulty.9
Operator experience has not been unanimously identified as an independent predictor of outcomes,2,5 but better results of EMR in the upper and lower GI tract are achieved in high-volume centers.10,11 Moreover, Swan and colleagues12 demonstrated that difficult polyps could be successfully managed by experts in 95% of cases, avoiding surgery in 90% of patients with high cost savings ($6990 per patient). Finally, a second-look by expert endoscopists is warranted before referring patients for surgery since most colorectal neoplasms can be managed by endoscopic resection.13–15
Data on the learning curve in colorectal EMR are scarce. Bhurwal et al16 demonstrated that 100 procedures are required to reach the learning curve plateau defined by 3 main outcomes: residual neoplasia at follow-up, incomplete EMR at resection, and immediate bleeding. The threshold for competency was unexpectedly high, probably because of the self-teaching methodology.
In conclusion, EMR is a procedure included in the standard training of GI fellows and performed routinely but real-life competency is suboptimal. Training protocols as well as retraining projects are warranted, and objective tools (eg, the DOPyS) should be used to provide effective means of assessing and certifying polypectomy. The difficulty of the procedure should be evaluated preoperatively, and difficult cases should be performed by experts or attempted under supervision.
Endoscopic Submucosal Dissection Training
ESD has become the preferred approach to GI superficial neoplasms in Japan and East Asia17 in spite of its higher technical demand. The high incidence of gastric cancer, its high detection rates in the early stage, and the lower level of difficulty in the stomach make Japan the ideal setting for training. Conversely, gastric ESD volumes in the West are small because of the lower incidence of gastric cancer and its more frequent diagnosis in advanced stages.18 The achievement of competence in the stomach before moving to more difficult locations is unrealistic, but it is equally unrealistic to unconditionally address esophageal and colonic neoplasms because adverse event rates would be very high.19,20 Fortunately, a protocol for Western operators can be proposed.20
High skills in lesion detection and characterization to assess risk of SM invasion and lymph node metastasis are required to properly select cases amenable for curative endoscopic resection. A low threshold for suspicion is of paramount importance for early gastric cancer that are frequently small, tiny, depressed and flat.21 A high proficiency is necessary to identify and delineate neoplastic lesions in the background of chronic gastritis and inflammatory bowel diseases, as well as low-profile sessile-serrated lesions, and to guarantee their complete resection.21,22 In a recent large, multicenter international study, Yao and colleagues23 demonstrated that an internet-based e-learning system could be an effective tool to improve the ability to diagnose gastric cancer at an early stage.
Endoscopy should be performed with a 2-hands technique with a high level of expertise, minimizing loop formation.24,25 Looping of the endoscope prevents effective transmission of twisting (torqueing) of the shaft to the tip and results in poor positional control.
Important skills necessary for a safe procedure include the ability to resect above semilunar folds, control the depth of cut, and avoid muscular injuries.
As part of training, it is also imperative to develop the skills for a systematic approach to the prevention and prompt management of intraoperative bleeding. Bleeding is commonly encountered and inversely correlated to competency, the probability of a complete resection, and safety (perforation risk). The precise identification of blood vessels and bleeding points is important for effective and safe hemostasis and maintaining a clear operative field. Competence in the management of endoscopic complications (eg, bleeding, perforation) is desirable and an integral part prior to undertaking endoscopic resection.26–28
Potential trainees for ESD should be selected according to their achievement of these propaedeutic skills. Since Western trainees are generally endoscopists with extensive background in interventional endoscopy, this could be an advantage over their Japanese counterparts, who are primarily young GI fellows.29 However, ESD is often associated with long operative times in the early phases of training, and not every skilled endoscopist is an appropriate trainee for ESD as this requires perseverance, an ability to perform at a high level during stressful situations, and to recognize one’s own limitations.30,31
A solid knowledge base is fundamental. The trainee should be aware of the basic dynamics of the procedure, appropriate approaches for each GI segment, mechanical properties and maneuverability of scopes and devices, management of adverse events, and histological assessment of specimens. The pedagogic approach to ESD in Japan and in the West starts to diverge from this phase. Japanese trainees observe and serve as assistants to experts in high-volume centers, becoming familiar with ESD “on the ground.”28 Western trainees can primarily interact with experts only at workshops and live course demonstrations and have to rely mostly on didactic material.
Nowadays, almost all Western ESD experts visit Japan at the beginning of their experience. High-volume Japanese centers generally schedule multiple ESDs per day that are performed both by trainees and experts. An observership period in these centers is ideal to become familiar with the whole spectrum of scenarios of real-time practice.32 Draganov et al32 demonstrated that ESD operating time significantly decreases in animal models after a 5-week observership in Japan, along with a trend toward decrease in failure to remove lesions and lower complication rate. Recently, Pioche and colleagues33 used a self-learning ESD software based on videos showing wrong and correct maneuvers as an expert’s observation surrogate. The use of this training software was effective in improving resection outcomes in animal models among untutored ESD trainees.
Operative training should proceed according to increasing difficulty gradients to reduce adverse events rates. The differences in the training protocol in Japan and in the West are particularly wide in this phase. Japanese trainees start their training by performing only a portion of the human ESD procedure conducted by experts.28 Marking, peripheral incision, and trimming are the first maneuvers, followed by dissection and understanding the orientation of the dissection plane. After achieving competency in these individual phases, a full ESD is begun under the supervision of experts who provide real-time guidance and can assist and take over the procedure if necessary. Skills and competencies are achieved through a stepwise approach that moves from the gastric antrum, the body and cardia, up to the esophagus and colon. The stomach is considered the easiest location for ESD because the large lumen facilitates scope maneuvering and the relatively thick wall minimizes the risk of perforation.34-36 The esophagus and colon show a significantly higher level of difficulty. The colon has a narrow windy lumen, multiple folds, and thinner walls. These anatomical features make endoscope positioning challenging and increase the risk of perforation. Studies on ESD learning curves from Japan show that a median of 30 gastric ESDs are required before independent completion of an entire procedure in the gastric antrum,26,37,38 40 to 50 procedures to achieve a proficiency in the middle and proximal stomach,39 and 80 to 100 procedures are necessary to achieve a high-level of expertise.27,28,40 Subsequently, a basic competency in colorectal ESD is reached after 30 to 40 procedures and more than 80 are necessary to achieve high-level mastery.41,42
The low incidence of gastric cancer in the West and thereby limited experiences for gastric ESD, in addition to the unique study by Probst and colleagues43 from Germany reporting colorectal ESD outcomes after gastric ESD competence, support the notion that adopting the Japanese training protocol is not feasible nor pragmatic in the West. Moreover, studies suggesting that training in colorectal ESD can be initiated without undertaking gastric ESD competence should be interpreted with caution. Outcomes were comparable (en bloc resection 72%; perforation rate 14%), but all trainees underwent the typical Japanese theoretic phase and practiced under expert supervision.24,44–46
The limits of the Western setting do not imply that a self-adjusted unsupervised learning path should ensue. As previously indicated, extensive experience in endoscopy is not a guarantee for good early ESD outcomes: Very high perforation rates in the stomach (22%) and esophagus (63%) were observed in animal models during short ESD workshops,47,48 as well as in a large French multicenter study that reported an overall 18% perforation rate for operators with limited experience.49 An alternative hands-on ESD training protocol for the West should include in a chronologic sequence: simulators (animal models), endoscopic hybrid resection techniques, and ESD in the rectum.
First Step: Animal Model Simulators
The use of animal models is optional in Japan but strongly recommended to Western trainees before transitioning to human cases.50 Ex vivo models are the most popular for the ease of setup and cheap cost, but live models may be beneficial for learning how to manage intraoperative bleeding in real time.51 The minimum number of ESDs to be performed in ex vivo animal models remains unclear because of methodological heterogeneities among studies. Nonetheless, most authors and experts suggest that 15 to 30 procedures could be sufficient for significant technical improvements.51–53 It is important to highlight that trainees included in these studies practiced under an expert’s supervision and this aspect limits the reproducibility of such results in a Western setting. Indeed, expert supervision has been clearly shown to significantly reduce operative time and contribute to skill acquisition.32,52 Bhatt et al54 evaluated the efficacy of a remote expert supervision model for Western trainees. One fellow and one expert endoscopist started their ESD training on ex vivo models and streamed the video of each procedure to Japanese experts, who provided feedback before each next session. The most important results of this video-based training system were the following: (1) competence was achieved after a similar number of procedures regardless of the different experience of the 2 operators; (2) most technical errors would have been difficult to resolve without expert intervention; and (3) subsequent ESDs in patients achieved curative en bloc resection without complications.
Second Step: Endoscopic Hybrid Resections
Endoscopic hybrid resection combines EMR and ESD phases and is differently defined according to the grade of hybridization: Circumferential incision (CI)-EMR is defined as a technique in which the outer margins of the lesion are incised with ESD knives followed by snare resection; hybrid ESD is defined as any technique in which any SM dissection is conducted up to a feasible snare resection. Hybrid resections were introduced to improve en bloc resection rates, therefore the indications for CI-EMR and hybrid ESD rely on lesion size. A prospective study on in vivo animal models suggested that CI-EMR could replace EMR for laterally spreading tumors (LSTs) < 40 mm with a 70% en bloc resection rate.55 On the other hand, results from a prospective study on humans were less promising, showing an en bloc resection rate by CI-EMR of only 6% for lesions measuring 30 to 40 mm.56 However, a complete resection was achieved in 1 or 2 pieces in 84% of cases, and the recurrence rate was 0% (much lower than the 10% to 26% reported when pieces are more numerous).57–59 Two retrospective studies showed that en bloc resection rate increases with an increasing grade of hybridization: 62% with CI-EMR and 65% to 91% with hybrid ESD.36,60 The training protocol could include hybrid resections as the initial step to achieve skills in some ESD phases. Competency in simulators does not equate to competency in humans, and hybrid resections can be used as a transition to the patient setting. Indeed, the possibility of including hybrid resections in the ESD training protocol has been evaluated in a study from South Korea.45 The ESD learning curve of a trainee with previous experience in CI-EMR showed an initial 72% en bloc resection rate and a 14% perforation rate.
Third Step: Endoscopic Submucosal Dissection in the Rectum
Initial human ESD cases should first be performed in easy locations. There are many advantages of starting Western ESD training in the rectum. Rectal tumors are more prevalent than early gastric cancers; the difficulty gradient in the rectum is similar to that in the stomach and significantly lower than in the colon. The rectum has a straight and large lumen, few folds, and is wrapped by the mesorectal tissue: These features decrease incidence and clinical relevance of perforations. Moreover, the difficulty of ESD in the upper and midrectum is similar to that in the gastric antrum, whereas that in the perineal rectum (close to the anorectal junction) is similar to that of ESD at the cardia. It should be noted that ESD in the rectum is safer but not absolutely easier than in the colon because of a higher frequency of intraoperative bleeding, a less durable SM lift, and the need for a retroflexed scope position when the neoplasm is located in the perineal rectum.
A propaedeutic competence in rectal ESD before moving to the colon has been suggested by Japanese experts and assimilated in a position paper by the European Society of Gastrointestinal Endoscopy.20 The feasibility and efficacy of this strategy have been demonstrated by Iacopini and colleagues in one study from Italy.61 The initial level of competence (defined as an 80% en bloc rate plus a significant increase inoperating speed) was achieved in the rectum after 20 procedures. Then, colonic ESDs were started and competence was achieved after 20 procedures. Perforation rates in the 2 locations were 3% and 8%, respectively. This study indicates that unsupervised Western endoscopists may complete the colorectal ESD learning curve within 50 procedures if skilled in colonoscopy and EMR, and after a 2-week observership in Japan and small experience in animal models (n.5 procedures). However, the initial low en bloc ESD resection rates (rectum 60%; colon 20%) and the long operative times (4 hours) suggest the need for more extensive experience in animal models, and perhaps a level of competency in rectal ESD greater than the basic before moving to colonic ESD.
Fourth Step: Endoscopic Submucosal Dissection Difficulty Stratification
The preceding training steps are conceived on the sequential acquisition of competence in different GI tract locations. However, ESD difficulty is related to multiple lesion features. Many Japanese studies have identified the following independent factors associated with difficult ESD: residual or ulcer-positive lesions in the colon and stomach, respectively,62–64 nongranular LST morphology in the colon,65,66 large lesion size,63,67 poor scope operability in the colon,65,68 and a low level of expertise.69 In a large series evaluating risks of noncurable gastric ESD, Hirasawa et al70 showed that lesion sizes of 20 to 30 mm (OR 2.2), > 30 mm (OR 6.3), location in the proximal stomach (OR 2.7), and presence of an ulcer (OR 2.7) were all independently associated with noncurative resection. Overall, small, nonulcerated lesions (≤ 20 mm) in the distal stomach may be appropriate for trainees whereas large ones (> 30 mm) or those with ulceration in the proximal stomach should be reserved for experts. A similar study by Iacopini and colleagues assessed ESD difficulty in the colon and rectum defined as piecemeal resection or slow procedure speed.71 A preoperative difficulty indicator in the rectum was the scar (OR 12.2); those in the colon were the scar (OR 12.7), and nongranular LST (OR 10.5) and sessile morphologies (OR 3.5); the threshold for a high-level mastery in colonic ESD was found at 120 procedures (OR 0.20). The combination of independent ORs was translated into probabilities of difficult colonic ESD for each neoplasm type: up to 47% for nongranular LSTs regardless of the presence of a scar and size; up to 23% for sessile polyps associated with a scar when experience is < 90 procedures, < 10% for granular LSTs.
The identification of the probability of ESD difficulty for each lesion type is valuable as it may permit breaking down the training protocol into more numerous steps to ensure education for trainees while safeguarding outcomes for patients. ESD learning curves are multiple: As endoscopists become more experienced, more challenging cases would be included with a distortion of the upper end of the learning curve.38
The introduction of ESD besides polypectomy and EMR pushes toward an accurate characterization of the superficial neoplasm to estimate the risk of SM invasion and lymph node metastasis and choose the appropriate resection strategy and the need of en bloc resection.
Polypectomy and EMR are routinely performed but the average level of competency is suboptimal. Training protocols and retraining projects are strongly recommended because incomplete resections contribute to up to 30% of interval colorectal cancers. The difficulty and complexity of endoscopic resection should be evaluated preoperatively by objective scores (eg, the DOPyS) and/or assessment charts.
The Western ESD stepwise training protocol is more complex than the Japanese one but it is almost standardized. Web-based didactic projects as well as exchange of videos with experts are warranted during the whole training to overcome the lack of expert supervision. The first step of the hands-on ESD phase should include animal models and endoscopic hybrid resections; the second easy neoplasms in easy locations (rectum and stomach); the third easy neoplasms in the colon and esophagus. Accurate prediction of the difficulty of any given ESD case based on lesion features may help streamline the training process. ESD outcomes are susceptible to multiple prognostics of difficulty, and a steady 85% en bloc resection rate and low (< 5%) perforation rate is achieved only after more than 200 cases.72 In general, the resection of large lesions should be performed by experts regardless of the choice between EMR and ESD.
Ultimately, competency should be assessed by quality outcomes (key performance indicators) rather than fixed procedure numbers that may not differentiate the degree of fellow involvement.54,73 Given all the accumulating data supporting the safety and efficacy of endoscopic resection in the hands of skilled operators, the next step is to formulate an official training protocol to help certify future endoscopists and help disseminate these techniques for the treatment of superficial GI neoplasia.30
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