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Endoscopy 2008; 40(12): 1026-1032
DOI: 10.1055/s-0028-1103414
Total Barrett Eradication review section

© Georg Thieme Verlag KG Stuttgart · New York

Argon plasma coagulation, bipolar cautery, and cryotherapy: ABC's of ablative techniques

J.  A.  Dumot1 , B.  D.  Greenwald2
  • 1Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, USA
  • 2Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine and Greenebaum Cancer Center, Baltimore, Maryland, USA
Further Information

B. D. GreenwaldMD 

Division of Gastroenterology and Hepatology

22 South Greene Street, Rm N3W62
Baltimore
MD 21201–1595
USA

Fax: +1-410-3288315

Email: bgreenwa@medicine.umaryland.edu

Publication History

Publication Date:
08 December 2008 (online)

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Table of Contents

A variety of endoscopic ablation modalities are available for the treatment of Barrett’s esophagus. Multiple studies have evaluated the use of argon plasma coagulation, mostly in nondysplastic Barrett’s esophagus. Significant variations in technique, end points, and follow-up exist between studies, but in most cases argon plasma coagulation is associated with unacceptable rates of persistent intestinal metaplasia and recurrence after completion of treatment. In addition, serious adverse events including perforation and stricture formation are reported. Multipolar electrocoagulation has been studied less thoroughly, but in prospective trials significant rates of persistent and recurrent intestinal metaplasia have also been reported. Lasers and heater probes have been tried in small numbers. Endoscopic cryotherapy ablation is a relatively new technique with studies focusing on high-grade dysplasia and early-stage cancer in high-risk patients. It has an acceptable safety profile, and early results show response in a significant number of patients in whom other modalities have failed.

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Introduction

”Ablation” literally means removing abnormal growths or harmful substances by mechanical means. Endoscopic ablation is most commonly discussed in the context of Barrett’s esophagus, with frequent reports in medical and popular journals; however, the most common use of endoscopic ablation by far is in the colon, with monopolar ”hot biopsy” forceps leading the pack. Generally speaking, methods of endoscopic ablation can be categorized as heat or cold injury and photochemical injury. Most heat injury is provided by electrical current using a catheter-based resistor (heater probe) or the tissue as the point of maximum resistance – bipolar or multipolar electrocautery (MPEC), hot biopsy forceps, argon plasma coagulation (APC), and radiofrequency. Other thermal injury provided by lasers or cryogens causes extreme temperature changes in the tissues. Photochemical injury is provided by the combination of a photosensitizing agent with intense light, often of a specific wavelength (photodynamic therapy, PDT).

Endoscopic ablation requires a treatment plan that considers several clinical characteristics such as the size, stage, location, and topography of the lesion or lesions. The patient’s overall medical condition must always be taken into consideration when dealing with well-established lesions, such as intramucosal cancer, because treatment failures or recurrences can be fatal. The difficulties in differentiating mucosal dysplasia as low-grade (LGD) or high-grade (HGD) or as intramucosal cancer (IMCA) within specialized intestinal metaplasia have been highlighted in reports of both surveillance and resection specimens. The unifying principle of endoscopic ablative therapy in Barrett’s esophagus is that mucosa tends to heal with normal squamous tissue after ablation with acid suppression; this is termed ”neosquamous” epithelium [1]. The origin of the new squamous epithelium is debated. Both untreated and treated patients have squamous overgrowth, but the risk of buried dysplastic epithelium or malignancy cannot be taken lightly, and guidelines for follow-up of patients have not been established.

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Argon plasma coagulation

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Technique

APC is a noncontact thermal 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). APC is applied to tissue until a white coagulum appears, and then the catheter and endoscope are manipulated in a vertical or circumferential linear pattern to coagulate additional tissue. The depth of tissue destruction is thought to be limited due to increased resistance and diminished current flow through coagulated tissue, although perforation has occurred with this device. The second-generation device (VIO/APC2) incorporates several improvements over the first-generation device [2]. The overall efficiency of the device is improved by 30 % – 50 %, so lower power settings can be used to produce the same thermal effects and, conversely, the same power settings may cause deeper and more extensive tissue injury than expected. Three different modes are now available on the device – 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 1 pulses approximately once per second, with higher energy output with each pulse, while effect 2 pulses approximately 16 times per second with lower energy output per pulse. The latter may be preferred when superficial treatment of large surface areas is desired. Precise APC utilizes an integrated regulation system to control the argon plasma. This results in a more superficial depth of injury compared to the other settings.

A variety of techniques have been reported for ablation of Barrett’s esophagus. The energy setting used in trials has varied from 40 to 90 W. In some studies, circumferential ablation of all metaplastic tissue was attempted, while in others noncircumferential ablation was performed or the length of tissue treated was limited. All patients were treated with acid suppression, typically with double-dose proton pump inhibitors. Some patients underwent Nissen fundoplication either before or after ablation for control of acid reflux. In some trials, 24-hour pH monitoring was performed to confirm acid suppression. The duration of acid suppression after ablation was also variable, although current trials generally maintain lifelong acid suppression to minimize the risk of developing new intestinal metaplasia in the esophagus.

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Results

Multiple prospective studies have examined the efficacy and safety of APC for Barrett’s ablation. The majority of these studies enrolled patients with Barrett’s esophagus without dysplasia [3] [4] [5] [6] [7] [8] [9] [10] [11], while a few have included patients with both LGD and HGD [12] [13] [14]. Considerable variation exists between studies in terms of energy used, end points, duration of follow-up, and use of chromoendoscopy to identify recurrent or persistent intestinal metaplasia.

In nondysplastic Barrett’s esophagus, APC was effective in completely eradicating intestinal metaplasia in 58 % – 100 % of cases, depending on the series. Recurrence was seen in most studies and was reported in 3 % – 66 % of patients followed. Subsquamous intestinal metaplasia (”buried Barrett’s”) was reported in some studies as well, although it was seen both in those in treatment and in observation groups. A randomized trial comparing APC to MPEC is described below under ”Bipolar or multipolar electrocoagulation” [4]. APC was used in patients with Barrett’s esophagus and HGD with a response in 25 of 29 patients (86 %) in one trial [12]. Four patients developed cancer and underwent repeat APC ablation. [Table 1] summarizes reports of APC for the ablation of Barrett’s esophagus.

Table 1 Treatment of Barrett’s esophagus with argon plasma coagulation: nondysplastic Barrett’s esophagus.
Author n Power, W Treatments, n Barrett segment length, cm Antacid regimen Follow-up, months Complete regression Recurrence Annual recurrence, %
Range Median Range Median Range Median n % n %
Bright et al. [3] 20 60 1 – 6 2.5 2–13 (Mean) 5.9 Nissen fundoplication – (Mean) 68 14 70 6/14 43 7.6
Dulai et al. [4] 26 60 – (Mean) 3.8 – (Mean) 4 Pantoprazole 40 mg BID – – 14 58 – – –
Ferraris et al. [5] 96 40 1 – 8 3.2 2.5 – 11 4 Omeprazole 40 mg/day 18 – 98 36 94 98 17/94 18 6.1
Madisch et al. [6] 73 90 – 2 1 – 12 4 Omeprazole 40 mg TID 9 – 85 51 69 98 8/66 12.1 3.0
Manner et al. [7] 60 90 1–8 (Mean) 2.7 1 – 8 (Mean) 3.6 Esomeprazole 40 mg BID 12 – 32 14 37 62 11/48 23 19.7
Mörk et al. [8] 25 60 1 – 12 4 2 – 10 3.8 PPI (various) 7 – 51 30 21 84 14/21 66 26.4
Schultz et al. [9] 79 90 1 – 5 2 1 – 12 4 Omeprazole 40 mg TID 2 – 51 12 69 94 0/69 0 0.0
Sharma et al. [10] 19 60 2 – 6 3 2 – 6 4 Rabeprazole 20 – 80 mg/day – – 12 63 – – –
Van Laetham et al. [11] 31 – 1 – 4 (Mean) 2.4 3 – 11 (Mean) 4.5 Omeprazole 40 mg/day 12 – 19 61 8/17 47 47.0
Attwood et al. [12] HGD: 29 70 1 – 13 2 – – – 7 – 78 (Mean) 37 25 86 4/25 16 5.2
Pereira-Lima et al. [13] BE: 18
LGD: 14
HGD: 1 		65 – 70 1 – 4 (Mean) 2 0.5 – 7 (Mean) 4 Omeprazole 60 mg/day 6 – 18 (Mean) 10.6 33 100 1/33 3 3.4
Ragunath et al. [14] LGD: 12
HGD: 1 		65 1 – 6 (Mean) 5 3 – 9 5 Lansoprazole 60 mg/day – 12 2 15 0/2 0 –
BID, twice a day; TID, three times a day; PPI, proton pump inhibitor; BE, Barrett’s esophagus; HGD, high-grade dysplasia; LGD, low-grade dysplasia; –, data not available.

Serious complications and less severe side effects have been reported. Perforation, often requiring thoracotomy, was reported in 0 % – 3.6 % of cases. Other serious adverse events include stricture (0 % – 15.4 %) and major bleeding (0 % – 3.9 %). Chest pain was reported frequently (1.8 % – 54.5 %), and one study reported dysphagia and odynophagia in over half the patients [13].

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Conclusion

Most experts do not recommend routine ablation of nondysplastic Barrett’s esophagus by APC or any other modality at this time. The relatively high incidence of complications, low rate of progression to cancer, and lack of long-term data on the effectiveness of eradication in preventing cancer progression confines ablation of nondysplastic Barrett’s esophagus to the research setting in most cases. Ablation of HGD in Barrett’s esophagus has been studied, but the limited data available in this patient group make it difficult to recommend APC for routine care. However, the availability of APC in most endoscopy units, ease of use, and endoscopists’ familiarity with the device make it useful as a ”touch-up” therapy to ablate small residual areas of intestinal metaplasia after treatment with other ablative techniques.

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Bipolar or multipolar electrocoagulation

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Technique

Ablation by MPEC requires contact with the mucosa across the electrode contacts at the tip of the catheter. Several generators are commercially available that provide variable output (usually around 50 W power) through both 10-Fr and 7-Fr endoscopic catheters. The 10-Fr catheter provides a slightly larger surface area. Bipolar cautery is favored by experts when the patient has an implantable device such as a pacemaker or automatic defibrillation generator, because the electrical current tends not to travel beyond the depth of thermal injury, unlike monopolar technology, which can disrupt the programming of these devices. The catheter is applied to the target mucosa and electrical current administered until a white coagulum is noted, similarly to APC.

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Results

Several early single-center trials have shown that MPEC can ablate Barrett’s esophagus [15] [16] [17] [18]. MPEC was evaluated in a prospective multicenter trial of patients with nondysplastic Barrett’s esophagus 2 – 6 cm long [19]. Patients were treated with omeprazole 40 mg twice daily and a 10-Fr gold probe set at 50 W up to a maximum of six sessions. Of the 72 patients enrolled, 58 reached a 6-month follow-up period, which found a 78 % complete response rate for elimination of Barrett’s esophagus. The mean number of treatments was 3.5, with a range of one to six sessions. Side effects included chest pain and one stricture requiring three dilation sessions. No long-term follow-up on the cohort is available.

A randomized controlled trial compared APC with MPEC in 52 patients [4]. After randomization, the length of the Barrett’s esophagus (BE length) was slightly greater in the APC group (n = 26) than in the MPEC group (n = 26; 4.0 cm vs. 3.1 cm, respectively, P = 0.03). BE length was limited to 2 – 7 cm, and patients were excluded if HGD or IMCA was present. All patients were treated with pantoprazole 40 mg twice daily. The APC treatment arm used a 10-Fr probe with 60 W power and 2 L/min gas flow. The MPEC treatment arm used a 10-Fr catheter and 16 W power. The APC group required slightly more sessions than the MPEC group (3.8 vs. 2.9, P = 0.04), but that analysis did not take the difference in BE lengths into account. Residual Barrett’s esophagus was found in both groups and response rates were similar (MPEC 81 % vs. APC 65 %, P = 0.21). Only the original BE length was related to complete response (n = 42) compared to incomplete response (n = 4); mean length in the complete response group was 3.3 cm (SD 1.4) compared to 6.0 cm (SD 2.2) in the incomplete response group (P < 0.01). After correcting for the original length, both technologies seem to allow physicians to treat approximately 1 cm of circumferential Barrett’s esophagus per endoscopic session.

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Conclusion

Bipolar electrocautery or MPEC was one of the earliest technologies applied to ablation of Barrett’s esophagus. No data exist to suggest that noncontact methods, such as APC or thermal laser, function any better than this widely available device. MPEC is suggested for ablation of focal areas of residual Barrett’s mucosa in patients with implantable devices.

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Cryotherapy

Cryotherapy is the application of extremely cold temperatures for medical treatment. The earliest reports of cryotherapy date back to 1850, when iced saline was used for palliation of breast, cervical, and skin cancers [20]. Several agents (cryogens) were tried until liquid nitrogen was introduced in 1950 by Allington, using a cotton swab applicator for skin lesions [21]. Liquid nitrogen (– 196 °C) is an ideal agent because it is inert, noncombustible, low in cost, and readily available. A large tank is available in most dermatology clinics, where both benign and malignant skin lesions are treated with liquid drops or spray. A cryosurgical probe was developed by Cooper and Lee using three concentric long tubes and a pressurized source of liquid nitrogen [22]. The inner tube supplied the liquid nitrogen flow to the tip; the middle space allowed return of the gaseous nitrogen and the outer tube served as a vacuum insulator. The similarity between the epidermis and esophageal mucosa is remarkable; delivery of the cryogens into the gastrointestinal tract has been the greatest challenge.

Two catheter devices have been developed by independent investigators with the goal of spraying cryogens through the working channel of an endoscope over a large surface area. The Polar Wand cryotherapy device (GI Supply, Camp Hill, PA, USA) involves a system with carbon dioxide. The first clinical use of the Polar Wand demonstrated the ability to cause tissue ablation but caused a pneumoperitoneum in a case of malignant gastric outlet obstruction [23]. The Polar Wand appears to be a safe and effective treatment for vascular lesions of the gastrointestinal tract [24] [25]. Early results of the carbon dioxide system in patients with Barrett’s esophagus and HGD or IMCA show promise with early data at a median follow-up of 3.9 months (range 1 – 8 months) [26]. The majority of available human data pertaining to ablation of esophageal mucosa are from the low-pressure system with liquid nitrogen and comprise the basis of the remainder of this limited review [27].

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Mechanism of action

Cryotherapy destroys biological tissue through a variety of methods [28] [29]. These can be divided into immediate and delayed effects. Rapid freezing causes failure of cellular metabolism due to stress on lipids and proteins. Continued freezing produces extracellular ice, creating a hyperosmotic extracellular environment and drawing fluid from cells. Further freezing produces intracellular ice formation, disrupting organelles and cell membranes. With thawing, ice crystals fuse and further damage cell membranes, and vascular stasis develops due to endothelial damage with edema, platelet aggregation, and formation of microthrombi. This results in ischemic necrosis. Repeated freeze–thaw cycles further increase tissue damage. At the periphery of the cryogenic lesion, immediate cell death may not occur. Delayed cell death due to apoptosis has been shown in cells located in this area, further increasing the ”kill zone.” An animal study compared the 1-hour histologic response to mucosal ablation with MPEC, APC, and cryospray ablation (CSA) [30]. At 1 hour, the epithelium of the esophagus treated with cautery devices was denuded but the area treated with the CSA remained intact. CSA causes minimal inflammation at 1 hour and hemorrhage into the muscularis mucosa and submucosa. Although the epithelium at 1 hour appears intact, the function and intracellular structure is damaged.

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Technique

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Device

CSA uses low-pressure liquid nitrogen spray delivered through a 7-Fr catheter passed through the working channel of a standard upper endoscope (CryoSpray Ablation System; CSA Medical, Inc., Baltimore, Maryland, USA). The console contains a holding tank for liquid nitrogen and the hardware necessary to regulate the flow of liquid nitrogen at 22 pounds per square inch (psi; 151.7 kPa) with catheter tip pressure of 3 – 6 psi (20.7 – 41.4 kPa). Foot pedals control the flow of nitrogen and suction during the procedure. The console controls include a timer to regulate dosimetry with auditory and visual cues and a catheter heater to assist in removal of the catheter at the end of the procedure. CSA is a noncontact technology that allows treatment of uneven surfaces and larger areas than APC or MPEC. Difficulties include the field of view with frosting of the lens, and treatment around the decompression tube. Using a friction-fit mucosectomy cap allows improved targeting of the cryospray to difficult areas and reduces the chance that the catheter will adhere to the adjacent mucosal surface.

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Dosimetry

The dosimetry of CSA is based on the duration of freeze time, as measured from the initial appearance of frozen mucosa in the area treated ([Fig. 1]). The first published data on the CSA device reported a dose response in 20 Yorkshire swine who demonstrated superficial mucosal necrosis, with complete healing after both hemicircumferential and circumferential spray [31]. Mucosal freeze occurred after the mucosal temperature reached 0° C to – 10 °C. The depth of injury, degree of inflammation, and rate of stricture development were greater in animals treated with circumferential spray and longer duration (30 – 60 seconds) cryospray than those treated with hemicircumferential and shorter-duration cryospray. A swine dosimetry study with 12 animals assessed the depth of injury and histologic response to varying cryospray times and numbers of cycles (unpublished data, on file at CSA Medical). Similar mucosal injury was induced with 10-second-duration cryospray using four freeze–thaw cycles compared to the longer 20-second-duration cryospray using two freeze-thaw cycles. Expansion of the nitrogen from the liquid to the gaseous state during a 20-second duration cryospray creates 7 – 8 L of gas at normal operating temperature and requires a decompression tube in the stomach prior to the start of each treatment. Reducing the spray time dramatically reduces the volume of gaseous nitrogen during the treatment cycle. Improvements from the manufacturer have increased the proportion of liquid nitrogen delivered to the target compared to gaseous nitrogen, which improved the ease of use.

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Fig. 1 Endoscopic cryotherapy ablation in the esophagus. A transparent cap is attached to the tip of the endoscope. The cryotherapy catheter is seen on the left side of the image. a Focal area of esophageal intestinal metaplasia. b Early freezing is seen on the target area. c Complete freezing of the target area is present. d Early thawing of the esophageal mucosa.

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Results

The first report of the CSA device as used in humans related to 11 patients with Barrett’s esophagus [32]. LGD was present in 5 patients and HGD in 1 patient. Patients received high-dose proton pump inhibitors (rabeprazole 40 mg three times a day) and underwent a mean of 4.2 sessions (range 1 – 8 sessions). In this pilot study, 9 of the 11 patients (78 %) had complete histologic reversal of Barrett’s esophagus, with no dysplasia found at 6-month follow-up. No significant complications occurred and the treatment was well tolerated. In a subsequent pilot study of CSA and endoscopic mucosal resection, 30 high-risk patients [median age 69 (62, 79; 25 – 75th percentile), 71 % male; median BE length 5 cm (2, 10; 25 – 75th percentile) (range 1 – 15 cm)], were treated with serial cryotherapy sessions every 6 weeks until there was resolution of HGD and IMCA [33]. This group of patients was characterized by a high incidence of prior endoscopic treatment failures or long segments of Barrett’s esophagus which exceeded the standard enrollment length of 2 – 6 cm. Eight patients had had prior ablation (2 APC, 2 PDT, 3 mucosectomy, and 1 both PDT and mucosectomy). The overall complete response (CR) of eliminating cancer or downgrading HGD dysplasia was 73 % for HGD and 80 % for IMCA (unpublished).

The ability to treat into the deep submucosa has enabled the use of cryotherapy in esophageal cancer, including Barrett’s-associated cancer ([Fig. 2]). The first case report of cryotherapy for esophageal cancer palliation demonstrated complete remission for 2 years in a patient with recurrent squamous cell carcinoma after combination chemoradiotherapy [34]. A case series of four patients with stage T1/T2 esophageal cancer who refused or failed to respond to conventional therapies were treated with cryotherapy for 3 – 11 months with 3 – 7 treatments. All patients responded, two of them demonstrating complete response with no visible tumor evident [35]. A multicenter registry is in development to further assess response in this setting, with results anticipated in 2009.

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Fig. 2 Endoscopic cryotherapy ablation of Barrett’s esophagus and invasive adenocarcinoma (T1sm) in an 86-year-old man. a The Barrett’s segment is 6 cm long with a 4-cm depressed area. b Endoscopic ultrasound confirmed that the tumor had invaded the submucosa without associated lymph adenopathy. c Biopsy confirmed poorly differentiated adenocarcinoma (H&E, × 10). d Follow-up endoscopy revealed a healed mucosa. e Surveillance biopsy was remarkable for focal intestinal metaplasia with low-grade dysplasia (H&E, × 10).

A recent prospective study evaluated the safety and tolerability of cryotherapy in 77 patients at four academic medical centers in the United States [36]. This group included patients with Barrett’s esophagus with HGD, LGD, no dysplasia, intramucosal carcinoma, invasive carcinoma, and severe squamous dysplasia. The most common side effects in 323 procedures included chest pain (17.6 %), dysphagia (13.3 %), odynophagia (12.1 %), and sore throat (9.6 %). Most symptoms were mild, and in almost half of procedures, no side effects were reported. The mean duration of symptoms was 3.6 days, with symptoms correlating to the length of treatment segment. Gastric perforation occurred in one patient with Marfan’s syndrome, probably as a result of gastric distension in the setting of abnormal collagen matrix in the stomach. Three patients developed esophageal strictures, and all responded to esophageal dilation. In Johnston’s original series of 11 patients, only two reported symptoms in 46 treatments. These included mild solid food dysphagia and chest discomfort, which resolved within 48 hours with only one patient requiring analgesia [32].

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Conclusion

Improvements to the current CSA technology will focus on three primary areas: directing the cryospray onto the target tissue, decompression to prevent over-insufflation, and dosimetry. Currently, treatment can be limited by patient tolerance and variables outside of the physicians’ control. Targeting lesions with unique catheters and improved methods of decompression will lead to a reduction in the number of sessions required to achieve a complete response. These technological advancements will improve dosimetry, with longer spray times being applied to thicker lesions, and provide therapeutic effect into deeper tissue levels.

The immune reaction induced by CSA may be the most exciting feature of this therapy. Other heat-based ablation methods such as APC and PDT tend to cause an eschar with denatured proteins compared to the apoptosis induced by CSA, which may lead to immune system stimulation, as crudely demonstrated by the inflammatory infiltrate visible on full-thickness histologic specimens. Adjuvant therapy may potentiate the immune response or induction of apoptosis of the target tissue.

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Lasers and thermal probes

Lasers have been studied in Barrett’s esophagus and esophageal cancer, including potassium–titanyl–phosphate (KTP), neodymium:yttrium–aluminum–garnet (Nd:YAG), and argon lasers. KTP laser treatment resulted in complete response in 10 patients with at least 4 cm Barrett’s esophagus with LGD (4 patients), HGD (4 patients), and IMCA (2 patients) [37]. An average of 2.4 sessions was required. Subsquamous specialized intestinal metaplasia was noted in two patients. Control of the laser output is a main advantage of the KTP system, which avoids injury to deeper tissue and perforation. The KTP emits a light with 532 nm wavelength that is preferentially absorbed by hemoglobin, making it useful for vascular lesions and other vascular tissue. Nd:YAG, emitting light at 1064 nm, provides a deeper penetration as it vaporizes tissue. Nd:YAG laser was used in conjunction with MPEC in six patients with IMCA who were deemed to be high-risk candidates for surgery [38]. All patients had a complete initial response and one developed a recurrence at 36 months. In a large prospective randomized trial of 236 patients with advanced esophageal cancer, PDT and Nd:YAG were overall similarly effective in palliation of dysphagia, although PDT has an advantage in upper and mid-thoracic tumors and for long tumors [39]. PDT was associated with fewer serious side effects (3 % vs. 19 %) excluding photosensitivity and perforations (1 % vs. 7 %). PDT will be discussed in more detail in another article in this special Barrett’s esophagus feature [40].

Thermal coagulation with a heat probe was used to treat 13 patients with nondysplastic Barrett’s esophagus 2 – 6 cm long [41]. Three of the 13 had subsquamous specialized intestinal metaplasia and two of the 13 had a relapse on follow-up thought to be due to noncompliance with acid suppression medications. One patient developed LGD during surveillance.

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Conclusions

Endoscopic ablation is a viable alternative to surgical resection for dysplasia and early-stage malignancies, especially in high-risk patients. Thermal devices (APC, MPEC, heater probe, and lasers) are cumbersome but effective for small areas. We believe the rate of incomplete eradication is similar for all ablative modalities. Future developments with cryospray ablation technology may improve outcomes especially with uneven surfaces, with dosing capable of reaching the submucosa. Proper histologic staging of irregular mucosal lesions with endoscopic mucosal resection is imperative in identifying candidates for endoscopic therapy, because invasive neoplasia beyond the lamina propria portends a poor prognosis with endoscopic therapy. Endoscopic mucosal resection also remains an excellent adjuvant therapy for residual disease after wide-area ablation. Treatment failures in endoscopic therapy and late recurrences are important factors to discuss with patients, especially in those with advanced neoplasia and reasonable operative risk. The gastric cardia remains the most difficult area to survey and in which to perform uniform ablation. No data are available to justify ablation of nondysplastic Barrett’s esophagus in terms of cancer risk reduction or long-term durability.

Competing interests: Both authors are consultants for and receive research support from CSA Medical

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    PubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
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    Search in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
  • 26 Canto M I, Dunbar K B, Okolo P. et al . Low flow CO2-cryotherapy for high risk Barrett’s esophagus (BE) patients with high grade dysplasia and early adenocarcinoma: a pilot trial of feasibility and safety [abstract].  Gastrointest Endosc. 2008;  67 AB179
    CrossrefPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
  • 28 Baust J G, Gage A A. The molecular basis of cryosurgery.  BJU Int. 2005;  95 1187-1191
    CrossrefPubMedSearch in Google Scholar
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    CrossrefPubMedSearch in Google Scholar
  • 30 Eastone J A, Horwhat J D, Haluska O. et al . Cryoablation of swine esophageal mucosa: a direct comparison to argon plasma coagulation (APC) and multipolar electrocoagulation (MPEC).  Gastrointest Endosc. 2001;  53 A3448
    PubMedSearch in Google Scholar
  • 31 Johnston M H, Schoenfeld P, Mysore J, Dubois A. Endoscopic spray cryotherapy: a new techique for mucosal ablation in the esophagus.  Gastrointest Endosc. 1999;  50 86-92
    CrossrefPubMedSearch in Google Scholar
  • 32 Johnston M, Eastone J A, Horwhat J D. et al . Cryoablation of Barrett’s esophagus: a pilot study.  Gastrointest Endosc. 2005;  62 842-848
    CrossrefPubMedSearch in Google Scholar
  • 33 Dumot J A, Vargo J J, Zuccaro G, Rice T W. Preliminary results of cryotherapy ablation for esophageal high grade dysplasia (HGD) or intra-mucosal cancer (IMC) in high risk non-surgical patients.  Gastrointest Endosc. 2007;  65 AB110
    PubMedSearch in Google Scholar
  • 34 Cash B D, Johnston L R, Johnston M H. Cryospray ablation (CSA) in the palliative treatment of squamous cell carcinoma of the esophagus.  World J Surg Oncol. 2007;  5 34
    CrossrefPubMedSearch in Google Scholar
  • 35 Greenwald B D, Cash B D. Cryotherapy ablation of early stage esophageal cancer.  Gastrointest Endosc. 2007;  65 AB276
    PubMedSearch in Google Scholar
  • 36 Greenwald B D, Horwhat J D, Abrams J A. et al . Endoscopic cryotherapy ablation is safe and well-tolerated in Barrett’s esophagus, esophageal dysplasia, and esophageal cancer.  Gastrointest Endosc. 2008;  67 AB76
    PubMedSearch in Google Scholar
  • 37 Gossner L, May A, Stolte M. et al . KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett’s esophagus.  Gastrointest Endosc. 1999;  49 8-12
    CrossrefPubMedSearch in Google Scholar
  • 38 Sharma P, Jaffe P E, Bhattacharyya A, Sampliner R E. Laser and multipolar electrocoagulation ablation of early Barrett’s adenocarcinoma: long-term follow up.  Gastrointest Endosc. 1999;  49 442-446
    CrossrefPubMedSearch in Google Scholar
  • 39 Lightdale C J, Heier S K, Marcon N E. et al . Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial.  Gastrointest Endosc. 1995;  42 507-512
    CrossrefPubMedSearch in Google Scholar
  • 40 Wang K K, Lutzke L, Borkenhagen L. et al . Photodynamic therapy for Barrett’s esophagus: does light still have a role?.  Endoscopy. 2008;  40 1021-1025
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 Michopoulos S, Tsibouris P, Bouzakis H. et al . Complete regression of Barrett’s esophagus with heat probe thermocoagulation: mid-term results.  Gastrointest Endosc. 1999;  50 165-172
    CrossrefPubMedSearch in Google Scholar

B. D. GreenwaldMD 

Division of Gastroenterology and Hepatology

22 South Greene Street, Rm N3W62
Baltimore
MD 21201–1595
USA

Fax: +1-410-3288315

Email: bgreenwa@medicine.umaryland.edu

#

References

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    CrossrefPubMedSearch in Google Scholar
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    PubMedSearch in Google Scholar
  • 21 Allington H V. Liquid nitrogen in the treatment of skin diseases.  Calif Med. 1950;  72 153-155
    PubMedSearch in Google Scholar
  • 22 Cooper I, Lee A. Cryostatic congelation: a system for producing a limited controlled region of cooling or freezing of biological tissue.  J Nerv Ment Dis. 1961;  133 259-263
    PubMedSearch in Google Scholar
  • 23 Pasricha P J, Hill S, Wadwa K S. et al . Endoscopic cryotherapy: experimental results and first clinical use.  Gastrointest Endosc. 1999;  49 627-631
    CrossrefPubMedSearch in Google Scholar
  • 24 Kalloo A. Colon – cryotherapy for radiation proctitis. The DAVE Project 2006 Available from: http://daveproject.org/viewfilms.cfm?film_id = 378. Accessed: 21 October 2008
    Search in Google Scholar
  • 25 Kantsevoy S V, Cruz-Correa M R, Vaughn C A. et al . Endoscopic cryotherapy for the treatment of bleeding mucosal vascular lesion of the GI tract: a pilot study.  Gastrointest Endosc. 2003;  57 403-406
    CrossrefPubMedSearch in Google Scholar
  • 26 Canto M I, Dunbar K B, Okolo P. et al . Low flow CO2-cryotherapy for high risk Barrett’s esophagus (BE) patients with high grade dysplasia and early adenocarcinoma: a pilot trial of feasibility and safety [abstract].  Gastrointest Endosc. 2008;  67 AB179
    CrossrefPubMedSearch in Google Scholar
  • 27 Johnston M H. Cryotherapy and other newer techniques.  Gastroint Endosc Clin N Am. 2003;  13 491-501
    CrossrefPubMedSearch in Google Scholar
  • 28 Baust J G, Gage A A. The molecular basis of cryosurgery.  BJU Int. 2005;  95 1187-1191
    CrossrefPubMedSearch in Google Scholar
  • 29 Gage A A, Baust J. Mechanisms of tissue injury in cryosurgery.  Cryobiology. 1998;  37 171-186
    CrossrefPubMedSearch in Google Scholar
  • 30 Eastone J A, Horwhat J D, Haluska O. et al . Cryoablation of swine esophageal mucosa: a direct comparison to argon plasma coagulation (APC) and multipolar electrocoagulation (MPEC).  Gastrointest Endosc. 2001;  53 A3448
    PubMedSearch in Google Scholar
  • 31 Johnston M H, Schoenfeld P, Mysore J, Dubois A. Endoscopic spray cryotherapy: a new techique for mucosal ablation in the esophagus.  Gastrointest Endosc. 1999;  50 86-92
    CrossrefPubMedSearch in Google Scholar
  • 32 Johnston M, Eastone J A, Horwhat J D. et al . Cryoablation of Barrett’s esophagus: a pilot study.  Gastrointest Endosc. 2005;  62 842-848
    CrossrefPubMedSearch in Google Scholar
  • 33 Dumot J A, Vargo J J, Zuccaro G, Rice T W. Preliminary results of cryotherapy ablation for esophageal high grade dysplasia (HGD) or intra-mucosal cancer (IMC) in high risk non-surgical patients.  Gastrointest Endosc. 2007;  65 AB110
    PubMedSearch in Google Scholar
  • 34 Cash B D, Johnston L R, Johnston M H. Cryospray ablation (CSA) in the palliative treatment of squamous cell carcinoma of the esophagus.  World J Surg Oncol. 2007;  5 34
    CrossrefPubMedSearch in Google Scholar
  • 35 Greenwald B D, Cash B D. Cryotherapy ablation of early stage esophageal cancer.  Gastrointest Endosc. 2007;  65 AB276
    PubMedSearch in Google Scholar
  • 36 Greenwald B D, Horwhat J D, Abrams J A. et al . Endoscopic cryotherapy ablation is safe and well-tolerated in Barrett’s esophagus, esophageal dysplasia, and esophageal cancer.  Gastrointest Endosc. 2008;  67 AB76
    PubMedSearch in Google Scholar
  • 37 Gossner L, May A, Stolte M. et al . KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett’s esophagus.  Gastrointest Endosc. 1999;  49 8-12
    CrossrefPubMedSearch in Google Scholar
  • 38 Sharma P, Jaffe P E, Bhattacharyya A, Sampliner R E. Laser and multipolar electrocoagulation ablation of early Barrett’s adenocarcinoma: long-term follow up.  Gastrointest Endosc. 1999;  49 442-446
    CrossrefPubMedSearch in Google Scholar
  • 39 Lightdale C J, Heier S K, Marcon N E. et al . Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial.  Gastrointest Endosc. 1995;  42 507-512
    CrossrefPubMedSearch in Google Scholar
  • 40 Wang K K, Lutzke L, Borkenhagen L. et al . Photodynamic therapy for Barrett’s esophagus: does light still have a role?.  Endoscopy. 2008;  40 1021-1025
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 Michopoulos S, Tsibouris P, Bouzakis H. et al . Complete regression of Barrett’s esophagus with heat probe thermocoagulation: mid-term results.  Gastrointest Endosc. 1999;  50 165-172
    CrossrefPubMedSearch in Google Scholar

B. D. GreenwaldMD 

Division of Gastroenterology and Hepatology

22 South Greene Street, Rm N3W62
Baltimore
MD 21201–1595
USA

Fax: +1-410-3288315

Email: bgreenwa@medicine.umaryland.edu

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Fig. 1 Endoscopic cryotherapy ablation in the esophagus. A transparent cap is attached to the tip of the endoscope. The cryotherapy catheter is seen on the left side of the image. a Focal area of esophageal intestinal metaplasia. b Early freezing is seen on the target area. c Complete freezing of the target area is present. d Early thawing of the esophageal mucosa.

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Fig. 2 Endoscopic cryotherapy ablation of Barrett’s esophagus and invasive adenocarcinoma (T1sm) in an 86-year-old man. a The Barrett’s segment is 6 cm long with a 4-cm depressed area. b Endoscopic ultrasound confirmed that the tumor had invaded the submucosa without associated lymph adenopathy. c Biopsy confirmed poorly differentiated adenocarcinoma (H&E, × 10). d Follow-up endoscopy revealed a healed mucosa. e Surveillance biopsy was remarkable for focal intestinal metaplasia with low-grade dysplasia (H&E, × 10).