Mucosal Ablation Techniques


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Mucosal Ablation Techniques


Fariha H. Ramay1, Bruce D. Greenwald1, Virender K. Sharma2, and John A. Dumot3


1 University of Maryland School of Medicine, Baltimore, MD, USA


2 Arizona Center for Digestive Health, Gilbert, AZ, USA


3 University Hospitals, Digestive Health Institute, Cleveland, OH, USA


Introduction


Ablation literally means to remove abnormal growths or harmful substances by mechanical means. Endoscopic mucosal ablation is typically performed using thermal energy devices employing radiofrequency ablation (RFA), argon plasma coagulation (APC), and cryotherapy. Training in endoscopic ablation involves developing an understanding of the mechanism of injury, risks, benefits, and alternatives of each modality. Practical considerations include experience with simple cases such as APC ablation of small mucosal lesions initially followed by more complex lesions once the endoscopist and assistants are familiar with the patient preparation and operation of the devices. Endoscopic ablation requires a treatment plan that considers several clinical characteristics such as the size, stage, location, and topography of lesion(s). Physicians must consider the patient’s overall medical condition when dealing with advanced lesions, such as intramucosal cancer, because treatment failures or recurrences can be fatal.


The unifying principle of endoscopic ablative therapy is that the ablated mucosa tends to heal with normal native epithelium. This chapter will discuss mucosal ablation in the context of esophageal intestinal metaplasia (Barrett’s esophagus [BE]). The principles for ablation of esophageal squamous dysplasia are similar. In BE patients, “neo‐squamous” epithelium forms after ablation in a reduced acid or acid‐free environment [1]. The origin of the new squamous epithelium is debated. All patients are treated with acid suppression, typically with twice‐daily proton pump inhibitors. Some patients receive antireflux procedures such as Nissen fundoplication before or after ablation for control of acid reflux. The duration of acid suppression after treatment is variable, although experts generally recommend lifelong acid suppression to minimize the risk of developing new intestinal metaplasia in the esophagus. The term total Barrett’s eradication refers to the tenet that once ablation has been pursued, attempts to remove all intestinal metaplasia from the esophagus and esophagogastric junction are the goal. Guidelines for the appropriate evaluation, treatment (including ablation), and follow‐up after ablation have been established [2]. It is now recognized that persistent or recurrent intestinal metaplasia is common and recurrent dysplasia and even cancer can develop years after ablation is complete [3,4].


This chapter considers the specific information about techniques that trainees need to master and discusses the optimal means by which they can develop the knowledge and skills needed to perform these procedures well.


Procedures and equipment involved in mucosal ablation


Endoscopic mucosal ablation is performed in the upper gastrointestinal (GI) tract via upper endoscopy. Careful evaluation of the esophageal mucosa is necessary during treatment and follow‐up, and this is best performed with high‐resolution endoscopes with virtual chromoendoscopy (narrowband imaging, FICE® [Fujifilm, Wayne, NJ], iScan® [PENTAX Medical, Tokyo, Japan]). Lugol’s iodine staining is more commonly used in the management of squamous lesions. There are specific specialized sets of tools for each ablative technique, and these will be described below.


Prerequisite cognitive and technical skills for trainees prior to learning mucosal ablation


Endoscopists should have expertise in identifying and treating early neoplastic lesions in the GI tract. An understanding of the advantages and disadvantages of endoscopic resection and different ablative treatment modalities is essential, as is appreciation of the importance of close follow‐up to detect ablation failures and treat them appropriately. Technical skills required include solid basic skills in upper endoscopy, proper biopsy technique for surveillance, identification of early neoplastic lesions using high‐definition scopes and virtual chromoendoscopy, endoscopic mucosal resection (EMR), and familiarity with the devices used to perform ablation (discussed below). (The acquisition of skill in virtual chromoendoscopy and interpretation of advanced imaging modalities are addressed in detail in a separate chapter in this volume.) The trainee in mucosal ablation should be trained to take full advantage of these image enhancements both to find the areas to ablate and to delineate the margins of these lesions accurately. Formal training to develop technical proficiency in endoscopic eradication therapy is needed. One such program is the American Society for Gastrointestinal Endoscopy (ASGE) STAR Certificate Program, which provides standardized education as well as hands‐on training in Barrett’s endotherapy skills (www.asge.org/home/education/advanced‐education‐training/star‐certificate‐programs#).


Setting of training


Mucosal ablation skills are best acquired in a high‐volume center where patients are seen in a multidisciplinary setting by experts in therapeutic endoscopy, thoracic surgery, medical oncology, and radiation therapy. A working relationship with colleagues in surgery and oncology is essential. Use of anesthesia personnel support should be strongly considered for these procedures, since they may be prolonged and uncomfortable to the patient.


Specific knowledge trainees must acquire during training to perform esophageal mucosal ablation


Patient selection


Patient selection for mucosal ablation requires a thorough understanding of the limitations of mucosal ablation techniques. Endoscopic resection is the preferred method of treating raised lesions. Training in a variety of ablation methods affords the endoscopist the option to use alternative techniques to manage difficult locations and topography. Trainees must develop a solid knowledge of indications and know when it is best not to treat at all and advise only ongoing surveillance. Understanding the pros and cons of such alternative options is needed for both optimal management decisions and providing thorough informed consent.


Selection of particular ablation method


To learn appropriate decision making about which specific ablative technique to use, trainees must consider existing literature, guidelines, and expert opinion about current options. No study has compared mucosal ablation techniques in a prospective fashion. The choice of ablation technique is typically based on endoscopist’s experience and patient preferences. APC should not be used as the primary treatment modality. It is useful for treating small focal areas of residual intestinal metaplasia after primary treatment. RFA and liquid nitrogen spray cryotherapy (LNSCT) have demonstrated efficacy in the treatment of BE with high‐grade dysplasia and intramucosal adenocarcinoma [3,4]. Balloon cryotherapy is a promising new ablation modality, although data on its efficacy is limited. In patients with dysplastic BE who are to undergo endoscopic ablative therapy for nonnodular disease, RFA is currently the preferred endoscopic ablative therapy based on current guidelines. RFA should not be used on nodular mucosa due to limited depth of injury with this modality. Patients with nodularity in the Barrett’s segment should undergo EMR of the nodular lesion as the initial diagnostic and therapeutic maneuver. In patients with EMR specimens showing high‐grade dysplasia or intramucosal adenocarcinoma, endoscopic ablative therapy of the remaining Barrett’s segment should be performed, even if no dysplasia is detected in the remaining Barrett’s tissue. Circumferential RFA should be used with caution in cases where endoscopic resection of more than one‐half the circumference of the esophagus is performed due to risk of mucosal laceration during balloon expansion. LNSCT should not be used in patients with retained gastric contents, in those who have undergone procedures to reduce or restrict gastric volume (such as gastric bypass or partial gastrectomy with gastrojejunostomy), or in those with diseases that significantly reduce elasticity of the GI tract (such as Marfan’s syndrome).


Anticoagulation considerations


ASGE guidelines discuss general management of antithrombotic agents for endoscopic procedures [5]. The risk of bleeding after mucosal ablation is low; however, this risk may be increased with the use of antithrombotic agents. Decisions on whether to continue these therapies during ablation must be individualized based on the patient’s risk of a thromboembolic event and the procedural risk of bleeding. Case reports with LNSCT suggest it can be safely performed on anticoagulation when necessary, since the mechanism of injury includes ischemic thrombosis of small blood vessels, limiting bleeding risk. Endoscopists may consider using the following approach if discontinuing anticoagulation is possible.


Warfarin


In patients with a low risk of thromboembolic events, warfarin may be stopped 3–5 days before the procedure and resumed the evening of the procedure. In high‐risk individuals, the use of intravenous or low molecular weight subcutaneous heparin may be used as bridge therapy while the INR is below the target level. As mentioned above, LNSCT has been performed successfully on patients actively taking warfarin therapy. Warfarin is generally restarted on the night of the procedure.


Heparin


Heparin should not be given on the day of the procedure.


Direct oral anticoagulants


These include direct factor Xa inhibitors (rivaroxaban [Xarelto], apixaban [Eliquis], edoxaban [Savaysa]) and direct thrombin inhibitors (dabigatran [Pradaxa], hirudins, and argatroban [Acova]). All of these should be held prior to endoscopy. Timing of discontinuation of rivaroxaban and apixaban is based on creatine clearance and ranges from 1 to 4 days prior to endoscopy. Edoxaban should be held for a minimum of 24 hours prior to endoscopy, with no data available for creatine clearance ≤15 mL/min. Timing of discontinuation of dabigatran is also based on creatine clearance and ranges from 1 to 3 days. These agents are generally restarted on the night of or day after the procedure.


Aspirin


Aspirin can be safely continued in patients undergoing endoscopic mucosal ablation.


Clopidogrel


In patients with a low risk of thromboembolic events, clopidogrel may be stopped 5 days before the procedure and resumed in 1–3 days following the procedure. In high‐risk patients, it may be continued, although the risk of bleeding post‐procedure may be increased. If clopidogrel is stopped, continuing or starting aspirin should be considered.


Acid suppression


Adequate acid suppression is critical for effective ablation of Barrett’s epithelium and is an important consideration in assessing possible causes of ineffective treatment. Proper acid‐suppressant therapy is important, not only to minimize patient discomfort but also to allow the esophagus to heal optimally and regenerate with squamous epithelium. All patients should be prescribed a high‐dose proton‐pump inhibitor twice a day 30 minutes before meals (omeprazole 40 mg twice daily, esomeprazole 40 mg twice daily, lansoprazole 30 mg twice daily, pantoprazole 40 mg twice daily, or dexlansoprazole 60 mg daily) beginning 1 week before ablation and continuing for at least 1 month after ablation is complete. H2‐receptor antagonists may be used for breakthrough or nocturnal symptoms. All patients should be queried for persistent heartburn symptoms on therapy, with alterations made in regimen if symptoms persist. The cause of incomplete regression to squamous mucosa after ablation is not clear, but consideration should be given to inadequate acid suppression. Ambulatory 24‐hour multichannel intraluminal impedance/pH monitoring on therapy can be helpful in confirming adequacy of acid suppression in problematic patients. Anti‐reflux surgery is helpful in patients with persistent reflux on maximal medical therapy or failure to respond to ablation.


Post‐ablation analgesia


Frequently, patients undergoing mucosal ablation require posttreatment medications to control pain, nausea, and dysphagia. After ablation, patients are advised to adhere to a liquid or soft diet overnight. A soft diet is continued if dysphagia or pain persists and can be advanced as symptoms dissipate. Citrus‐ and tomato‐based products can also cause symptoms and may be avoided. Patients may experience symptoms of chest discomfort, sore throat, difficulty or pain with swallowing, and nausea, which usually improve each day. Sucralfate suspension is helpful to control pain after ablation and is routinely prescribed in many centers. Lidocaine oral solution (sometimes mixed with liquid antacid and/or diphenhydramine solution), liquid acetaminophen with or without codeine or hydrocodone, and antiemetic medication are often helpful to palliate severe symptoms. Patients are advised to avoid alcoholic beverages during the healing process, which typically takes at least 2 weeks. Some patients may develop severe chest pain and fever. Inpatient observation and conservative management with an intravenous proton pump inhibitor, analgesic regimen, and hydration usually suffice in these cases. Severe dysphagia with inability to tolerate medications and fluids should prompt an urgent endoscopic exam due to the possibility of an acute inflammatory stricture requiring dilation. Trainees must also be mindful to prepare patients for these specific post‐ablation symptoms and their management during the consent process.


Pacemakers and implantable cardiac defibrillators (ICDs)


In general, pacemakers are not affected by RFA techniques, which involve the use of bipolar current. (Training in electrosurgical principles is covered separately in Chapter 12.) Implantable cardiac defibrillators (ICDs) may be affected by monopolar coagulation such as APC, less commonly by bipolar coagulation. All patients should undergo standard cardiac monitoring during the procedure. The grounding pad for APC should not be placed near a pacemaker or ICD. Cardiology consultation is recommended before performing APC or RFA in a patient with an ICD or pacemaker to determine proper management during the procedure. Typically, the ICD is temporarily deactivated by appropriately trained personnel before performing APC, and external defibrillation may be necessary in the event of a life‐threatening arrhythmia during treatment. The ICD is reactivated immediately after the procedure.


Post‐ablation surveillance


No study has validated the appropriate surveillance interval or proper biopsy protocol after successful ablation. For BE with high‐grade dysplasia or intramucosal adenocarcinoma, surveillance intervals after successful ablation are typically every 3 months for the first year, every 6 months in the second year, and annually thereafter [2]. In patients with low‐grade dysplasia, post‐eradication surveillance is recommended every 6 months in the first year and annually thereafter. Many continue annual surveillance if there is benefit to continued surveillance, with cessation when surveillance is no longer felt to be useful (severe medical issues, short anticipated survival). At each endoscopy, careful examination of the treated esophageal segment and area below the squamocolumnar junction should be performed with a high‐resolution endoscope and virtual chromoendoscopy. Careful inspection should be performed of the right hemi‐circumference of the Barrett’s segment (from the 12 o’clock to 6 o’clock location) where early cancer has a predilection to develop. Flat areas of intestinal metaplasia should receive endoscopic ablation. Any nodules, both within the treated area and in the gastric cardia, should be removed by EMR. Surveillance biopsies should be taken at each endoscopy with large capacity biopsy forceps. Current guidelines recommend performing biopsies of any abnormal appearing areas and in four quadrants every 1 cm within the treated segment in what is now normal‐appearing squamous mucosa. More recently, some experts recommend only performing four quadrant biopsies 1 and 2 cm above the squamocolumnar junction in addition to targeted biopsies of abnormal areas. Biopsies should also be taken in four quadrants just below the squamocolumnar junction to assess for residual intestinal metaplasia in the esophagogastric junction and cardia.


Equipment and technical steps


Argon plasma coagulation


APC is a noncontact technique using ionized argon gas to deliver a monopolar high‐frequency current, which effectively coagulates tissue. The APC device and endoscopic catheter most commonly used are manufactured by ERBE Elektromedizin GmbH (Tübingen, Germany). The depth of tissue destruction is thought to be limited by increased resistance and diminished current flow through coagulated tissue, although perforation has occurred with this device. Three different modes are available—forced, pulsed, and precise. Forced APC provides continuous output and corresponds to settings on the earlier system. Pulsed APC provides intermittent current with two options. Effect one setting pulses approximately once per second, with increasing energy output with each successive pulse. Effect two pulses approximately 16 times/second with lower energy output per pulse. This may be preferred when superficial treatment of large surface areas is desired. Typically, effect two has been used for Barrett’s ablation [6]. Reports have used power setting ranging from 30 to 90 W, with more recent studies [7] utilizing 60–70 W. Trainees must acquire detailed knowledge of the settings for the generator in their unit and how these settings can be accessed. Successful trainees must not rely upon endoscopy nurses and technicians for specific information regarding electrosurgical generators, accessories, and how to use them.

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Jul 31, 2022 | Posted by in GASTOINESTINAL SURGERY | Comments Off on Mucosal Ablation Techniques
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