Approach Considerations
Before endoscopic resection is initiated, the extent of the target lesion should be clearly established. Once resection has commenced, mucosal landmarks may be obscured. Furthermore, visible abnormalities in early neoplastic lesions are often difficult to ascertain. Saline or water irrigation is often used; spraying of 1% acetylcysteine aids in the dissipation of adherent mucus. A combination of magnification high-definition white-light endoscopy and narrow-band imaging or chromoendoscopy (see the image below) is useful.
Superficial gastric neoplasm (arrow) demonstrated with chromoendoscopy prior to cap-assisted endoscopic mucosal resection (EMR).
Additional techniques include confocal laser endomicroscopy and optical coherence tomography/volume laser endomicroscopy; these techniques are not yet widely available. The periphery of the lesion may be marked using superficial cautery marks.
Endoscopic Mucosal Resection (EMR)
Several endoscopic mucosal resection (EMR) techniques have been developed, all of them based on the principles of “lifting” the target mucosa and resecting the lesion by applying the cautery (see the image below). The main approaches are as follows:
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Injection-assisted EMR
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Cap-assisted EMR
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Ligation-assisted EMR
Early work with another variant, "underwater" EMR, has suggested that this approach may prove to be an effective and safe alternative to traditional EMR. [65, 66, 67, 68]
Injection-assisted EMR
The injection-assisted (or “inject-and-cut”) technique consists of submucosal injection of an aqueous solution followed by the application of a snare cautery for lesion resection. [69] Submucosal injection is a well-established technique that creates a submucosal cushion underneath the lesion, mitigating the risk of transmural thermal injury during the application of cautery.
The solution is delivered via a standard injection needle. The underlying principle is that the solution will “seek” the submucosal layer because of the presence of loose connective tissue within this layer. An automated pump is commercially available that facilitates uniform submucosal injection (ERBE, USA). A modification of this technique, the “inject-lift-and-cut” technique or “strip biopsy,” uses a tissue grasper passed through a second working channel to provide traction on the target mucosa during resection.
Typically, 5-50 mL of solution is injected beneath the lesion. During colonic EMR, injection of the distal margin of the lesion first often aids visualization during resection. The addition of dilute staining dyes (eg, indigo carmine or methylene blue) assists in identification of the deep and lateral resection margins. [70]
Results with saline, the most commonly used solution, are often limited by the relatively rapid absorption of the injection; thus, multiple injections are often necessary. This problem has been addressed by the invention of combination needle and snare devices, as well as the study of various injection solutions. The addition of dilute epinephrine to standard saline provides a limited increase in cushion durability.
Other solutions that have demonstrated longer-lasting cushions include hyaluronic acid, hydroxypropyl methylcellulose, glycerol, and fibrinogen solutions, though most are not widely available and are limited by cost considerations. [71, 72, 73] It is noteworthy that injection of autologous blood has shown superior results with respect to cushion durability. [74, 75] An increased incidence of local inflammatory reactions has been demonstrated with the use of hypertonic saline, hypertonic dextrose, and hydroxypropyl methylcellulose, limiting their use in practice.
A systematic review and meta-analysis assessed injection of normal saline against injection of other viscous and hypertonic solutions (eg, hydroxyethyl starch, sodium hyaluronate solution, 50% dextrose, and succinylated gelatin) in the setting of EMR for colorectal polyps. [76] Compared with normal saline, other viscous solutions were associated with a significant increase in en-bloc resection and a significant decrease in residual lesions. Overall adverse events rates did not differ significantly between the two groups.
Because there were no significant outcome differences for lesions smaller than 2 cm, the authors of this study suggested that endoscopists might consider using normal saline for EMR of smaller (< 2 cm) colorectal polyps and other viscous solutions for larger (>2 cm) colorectal polyps. [76]
Cap-assisted EMR
This technique uses a combination of submucosal injection, aspiration of tissue into a clear soft plastic cap attached to the tip of the endoscope, and snare excision. [77]
Various single-use devices that include a combination of cap and specially designed snare are commercially available. Typically, the snare is opened within the distal internal rim of the cap, tissue is aspirated within the cap and snare, the snare is closed around the captured tissue, and a standard snare cautery is applied to excise the tissue. Caps are available in various sizes and have either a flat (cylindrical) or oblique end, with the latter assisting in tissue aspiration within the tubular esophagus (see the image below).
Ligation-assisted EMR
Born from the extrapolation of tissue acquisition during variceal band ligation to EMR, this technique involves the application of bands around aspirated tissue and subsequent snare-cautery resection. In theory, the band incorporates the mucosal and submucosal layers while leaving the muscularis propria in situ as a consequence of insufficient contractile force.
In the simplest form of the procedure, a standard variceal band ligator device is used to aspirate the target lesion and apply a band around it (see the images below). After removal of the banding device, a separate snare is used to resect the lesion. [78, 79]
Endoscopic mucosal resection (EMR). Aspiration of tissue during ligation-assisted EMR.
A submucosal injection may also be made before tissue aspiration, though this step is not universally performed. Two EMR kits that are commercially available in the United States include a modified multiband ligator and hexagonal snare that is passed within the working channel with the ligation device in place.
Practice variations in technique include the following [80] :
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Use of saline lift before EMR
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Closure of the snare above vs below the band
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Initial application of multiple bands vs resection following the application of each band during resection of larger lesions
Endoscopic Submucosal Dissection (ESD)
The video below illustrates endoscopic submucosal dissection (ESD) in the stomach.
The procedure of ESD may be divided into the following four steps:
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Definition of margins
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Marking of mucosal borders
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Circumferential incision
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Submucosal dissection
Step 1: definition of margins
Most lesions can be accurately defined with high-definition white-light imaging (see the image below) and/or narrow-band imaging and/or chromoendoscopy with 0.5% methylene blue application. Squamous cell carcinoma (SCC) of the esophagus can be defined better with Lugol solution.
Endoscopic submucosal dissection (ESD). Mucosal lesion defined with high-definition white-light imaging.
Step 2: marking of mucosal borders
Once the lesion is lifted with submucosal injection, the borders of a lesion can be obscured. Therefore, thermal mucosal marking is done with the tip of the snare or a needle-type ESD knife (see the image below).
Step 3: circumferential mucosal incision
After mucosal marking is done, a submucosal injection is performed with injection solutions. After the lesion is lifted from the muscle layer, the initial mucosal incision is done with a needle-type ESD knife or the tip of a snare. The mucosal incision is then extended circumferentially (see the image below).
Step 4: submucosal dissection
After the circumferential incision, the exposed submucosal layer is further injected with ESD injection solutions. With the distal attachment of the scope used to create countertraction, the endoscope is advanced into the submucosal space. The dissection of the submucosal layer is then performed parallel to the muscle layer until the lesion is safely removed. (See the images below.)
Postprocedural Care
EMR is primarily performed on an outpatient basis. After the procedure, patients typically receive general instructions regarding medication use, diet, and symptom management. Patients undergoing upper EMR may be prescribed a clear liquid diet on the day of the procedure with diet advancement as tolerated thereafter.
On the other hand, most centers performing ESD admit patients for a significant period after the procedure. [81, 82] However, a number of expert centers have reported safe performance of outpatient-based ESD. [83, 84, 85, 86]
Infrequently, patients may experience pain that can be managed with nonnarcotic analgesia. Management of anticoagulants and antiplatelet agents should be discussed with the prescribing provider before the day of the procedure. These agents are generally stopped beforehand at an interval that allows return to normal clotting and coagulation function in advance of the procedure; they are generally restarted shortly after the procedure. Cessation of aspirin is not necessary before EMR; however, it is controversial whether continued use of aspirin is a risk factor for bleeding after ESD. More data on ESD bleeding risk and aspirin intake are needed. [87]
Patients should be instructed to seek medical attention if they experience fever, nausea or vomiting, hematochezia, or melena.
It is recommended that all patients receive high-dose proton pump inhibitor (PPI) therapy after gastric lesion resections. A study from South Korea that included 56 patients who underwent ESD for either gastric adenoma or early gastric cancer (EGC) revealed that the degree of healing of ESD-induced ulcers was associated with the initial ulcer size. [88] Accordingly, it was recommended that patients with ESD-induced ulcers larger than 40 mm receive 4 weeks of PPI treatment with pantoprazole 40 mg once daily.
Complications
Although EMR and ESD are generally safe in experienced centers, several complications have been described.
Bleeding
Bleeding is the most common complication of EMR and ESD and consists of intraprocedural bleeding and delayed bleeding, which can occur from 6 hours to 7 days after procedure. Immediate bleeding has been identified as an independent predictor of delayed hemorrhage. [89, 90]
Choi et al compared the complications of ESD and EMR for gastric neoplasms and found a higher risk of bleeding in the ESD group; furthermore, bleeding in the ESD group required more attention than that in the EMR group. [91]
Bleeding rates also vary, depending on the location of the lesion. Bleeding in the esophagus is uncommon, with one large study reporting significant bleeding necessitating intervention, transfusion, or hospitalization in 1.2% of patients undergoing this procedure. [92, 93] Intraprocedural bleeding rates for gastric EMR range from 0% to 11.5%, with delayed bleeding occurring in approximately 5% of patients. [92] Intraprocedural bleeding rates after EMR of colorectal lesions larger than 20 mm range from 11% to 22%. Bleeding rates after EMR of large colonic polyps range from 2% to 11%. [92]
Immediate bleeding is typically managed with hemostatic endoscopic clips, hot biopsy forceps, monopolar hemostatic forceps, bipolar coaptive coagulation, argon plasma coagulation, or soft coagulation with the tip of a snare. Prophylactic clip placement has been suggested as a means of reducing delayed polypectomy bleeding after EMR of large colorectal lesions. [94]
Perforation
Perforation is a rare complication of EMR, with reported rates of 0.3-0.5% for esophageal and colonic EMR [95, 96] and 1% for gastric EMR. [97] ESD, however, has a relatively higher risk of perforation, with reported rates of approximately 3%. [98] Small perforations are amenable to endoscopic closure with endoscopic clips. [99, 100, 101] Urgent surgical consultation and intravenous (IV) broad-spectrum antibiotics are indicated for larger defects.
Endoscopic suturing of large mucosal defects, typically performed after ESD, has also been utilized. [102] Endoscopic tissue shielding with polyglycolic acid sheets has been described in two cases of large perforations not eligible for endoscopic closure as a possible option for large perforations after esophageal endoscopic resection. [103]
Stricture
Stricture formation is a late complication following endoscopic removal of esophageal lesions and has been reported in 5-88% of patients. [104, 105, 106, 107, 108, 109, 110, 111] Esophageal strictures are more common after resection of multiple lesions and large resections occupying three quarters of the luminal circumference or resection lengths in excess of 3 cm. [108] Strictures respond well to serial endoscopic dilation.
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Principles of mucosal resection.
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Schematic of lesion penetration as determined by high-frequency endoscopic ultrasonography (EUS).
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Endoscopic view of superficial gastric neoplasm.
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Probe-based high-frequency ultrasound image of superficial gastric neoplasm.
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Transparent endoscopic mucosal resection (EMR) cap.
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Endoscopic mucosal resection (EMR). Resection specimen reveals negative deep and lateral margins.
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Endoscopic mucosal resection (EMR). Aspiration of tissue during ligation-assisted EMR.
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Superficial gastric neoplasm (arrow) demonstrated with chromoendoscopy prior to cap-assisted endoscopic mucosal resection (EMR).
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Endoscopic mucosal resection (EMR). Combined cap-and-snare device.
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Paris classification of superficial gastrointestinal neoplasms.
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This video, captured via esophagogastroduodenoscopy, shows use of HALO 90 device to perform radiofrequency ablation in patient with Barrett esophagus. Barrett esophagus increases risk of developing esophageal cancer. Video courtesy of Dawn Sears, MD, and Dan C Cohen, MD, Division of Gastroenterology, Scott & White Healthcare.
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This video shows circumferential Barrett esophagus via esophagoscopy. HALO 360 device is in esophageal lumen, ready to perform radiofrequency ablation. Video courtesy of Dawn Sears, MD, and Dan C Cohen, MD, Division of Gastroenterology, Scott & White Healthcare.
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This video, captured via esophagoscopy, shows Barrett esophagus after having just undergone treatment with radiofrequency ablation using HALO 360. Video courtesy of Dawn Sears, MD, and Dan C Cohen, MD, Division of Gastroenterology, Scott & White Healthcare.
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This video, captured via esophagoscopy, shows long circumferential segment of Barrett esophagus. Video courtesy of Dawn Sears, MD, and Dan C Cohen, MD, Division of Gastroenterology, Scott & White Healthcare.
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Endoscopic submucosal dissection (ESD). Mucosal lesion defined with high-definition white-light imaging.
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Endoscopic submucosal dissection (ESD). Thermal mucosal marking of lesion.
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Endoscopic submucosal dissection (ESD). Circumferential mucosal incision.
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Endoscopic submucosal dissection (ESD). Submucosal dissection.
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Endoscopic submucosal dissection (ESD). Completion of submucosal dissection
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Endoscopic submucosal dissection (ESD): stomach.
Tables
| Depth | Esophageal Squamous Cell Carcinoma | Esophageal Adenocarcinoma | Gastric Adenocarcinoma | Colonic Adenocarcinoma |
|---|---|---|---|---|
| M1 | 0% | 0% | 0-0.4% | 0% |
| M2 | 0.03% | |||
| M3 | 9% | 0.02% | ||
| Sm1 | 15-20% | 200 μm 1.9% (if lesion is < 2 cm) | up to 500 μm < 3% | 1000 μm < 1% |
| Sm2 | 10% without risky signs 33% with risky signs |
~20% | 6% | |
| Sm3 | 14% |
