Is there a role for ablative therapy to treat BO?

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Is there a role for ablative therapy to treat BO?

Introduction

There is considerable interest in the possibility of ablating the Barrett's mucosa in an effort to reduce the risk of progression to malignancy and perhaps obviate the need for ongoing endoscopic surveillance. There have been a number of endoscopic therapies that have been studied to ablate Barrett's mucosa. These have mostly been tested in patients with non-dysplastic mucosa (see also Are there any treatments that prevention progression of BO to cancer?).

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Photodynamic therapy

Photodynamic therapy involves the administration of a photosensitiser drug and then subsequent exposure of the target tissue (Barrett's mucosa) with a laser light. There are two photosensitisers that have been mainly studied and these are aminolevulinic acid (given orally) and Photofrin (given intravenously). The studies have all been published in North America and Europe due to the potentially severe skin sensitivity that arises after administration of the photosensitiser. In the case of aminolevulinic acid this can last days and for Photofrin possibly months. During this time the subject must remain in a darkened environment. This issue restricts the use of this technology to cooler climate countries. Studies comparing the photosensitisers and various doses and times of administration favour aminolevulinic acid over Photofrin as being more effective.[1] Most published studies however are small and methods vary widely making comparisons difficult.[2] One study includes a large number of patients from 30 centres in four countries.[2] This study may be prone to institutional variations and inconsistent application of the study protocol. Photodynamic therapy is able to reliably ablate Barrett's mucosa and in up to 77% of patients there is complete ablation.[3][4] Comparisons have been made between photodynamic therapy and argon plasma coagulation but a clear difference has not been established.[5][6][4]

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Argon plasma coagulation

Argon plasma coagulation (APC) is a widely available monopolar electrocautery device where argon gas is passed through a fine catheter inserted through the channel of an endoscope. As the gas leaves the catheter it passes over a high voltage electrode which electrifies the gas producing argon plasma. This plasma conducts the electrical energy to the target tissue without physical contact. The benefit of the system is that it produces superficial coagulation of the target tissue without injuring deeper layers of the gut wall. APC has been shown to effectively ablate Barrett’s mucosa and mucosal eradication of greater that 95% has been reported in the majority of subjects (97% of treated patients).[7][8][9][10] Randomised controlled studies show that both medically treated patients and those with prior successful fundoplication can be cleared of Barrett’s mucosa whereas control patients do not show significant regression.[7][8][9] Long term data to >84 months shows some relapse of Barrett’s mucosa but 65% of patients have no evidence of Barrett’s mucosa.[11] APC has been compared to PDT[5][6] and multipolar electrocoagulation therapy,[12][13] but no significant differences have been identified. APC is safe but isolated reports of oesophageal stricture formation and oesophageal perforation have been reported. The majority of studies examining APC have treated non-dysplastic Barrett’s mucosa.

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Multipolar electrocoagulation

Multipolar electrocoagulation (MPEC) is a bipolar technique using a catheter passed through the channel of an endoscope. The catheter has a number of electrodes on its tip. Electrical current is passed between the electrodes through the adjacent target tissue causing thermal coagulation of the tissue. The current is confined to the mucosal surface and therefore only mucosal destruction is seen with sparing of the deeper layers. The type of mucosal effect is similar to that of APC. MPEC has been compared to APC and these two techniques have been found to have comparable efficacy in ablation of Barrett’s mucosa.[12] MPEC may require slightly fewer treatment sessions than APC and be quicker to perform. Safety of MPEC therapy appears to be good and long term follow up suggests the results are similar to that seen in patients treated with APC. The majority of studies examining MPEC have treated non-dysplastic Barrett’s mucosa.

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Cryotherapy

Cryotherapy for Barrett’s mucosal ablation involves spraying the oesophageal mucosa with either liquid nitrogen or pressurised CO2 gas. The mucosa is ablated by freezing the superficial layers. The equipment required is bulky, expensive and highly specialised and at this stage not readily available outside research centres. Initial studies were performed using liquid nitrogen but this is relatively hazardous equipment to use as catheter dysfunction could cause injury to staff and equipment. More recent studies use pressurised CO2 which is technically easier to administer. Reported safety seems good but significant treatment side effects include chest pain, dysphagia and odynophagia. These symptoms can last a number of days. Studies have been performed only for dysplastic Barrett's mucosa.[1]

Radiofrequency ablation

Radiofrequency ablation (RFA) of Barrett’s mucosa has received the most rigorous study of all the ablation techniques. RFA involves placement of a balloon catheter in the oesophagus. Around the circumference of the balloon are fine electrodes through which radiofrequency energy is delivered allowing treatment of a 3cm circumferential segment of the oesophagus. Balloon position is monitored with an endoscope and treatment of the entire Barrett’s segment is generally possible in one session. The procedure is relatively easy and quick to perform and is well tolerated by patients. Side effects include chest pain, dysphagia and stricture formation. Rare complications such as bleeding and perforation have been noted. The RFA catheters are single use and relatively expensive limiting broad application of this technology. Well-designed randomised sham controlled studies have shown high levels of eradication of both non-dysplastic (>90%) and dysplastic (>90%) Barrett’s mucosa.[1] Long term follow up studies show the response is durable with the majority of patients (>85%) maintaining complete eradication over a five year follow up period. RFA has been compared to PDT and has been shown to be more effective at Barrett’s mucosal ablation. Studies have been performed in patients whose reflux disease was treated medically or managed with surgical fundoplication and the outcome was similar in these two groups.

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Evidence summary and recommendations

Evidence summary Level References
There are a number of therapies that are able to ablate Barrett's mucosa but ablation is incomplete in a number of patients and relapse of the Barrett's mucosa over time means that ongoing surveillance endoscopy is still required. The prognosis of patients who have achieved complete eradication of Barrett's mucosa after ablation is not known. I, II [1], [3], [4], [6], [11], [12], [13]
Evidence-based recommendationQuestion mark transparent.png Grade
Long term outcome studies do not yet support ablation in patients without dysplasia.
B


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Issues requiring more clinical research study

  • The long term outcome of ablation of non-dysplastic Barrett's mucosa needs to be studied to assess the durability of the ablation therapy and determine if there are any patients who subsequently no longer need follow up in Barrett's surveillance programs.

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References

  1. 1.0 1.1 1.2 1.3 Rees JR, Lao-Sirieix P, Wong A, Fitzgerald RC. Treatment for Barrett's oesophagus. Cochrane Database Syst Rev 2010 Jan 20;(1):CD004060 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20091557.
  2. 2.0 2.1 Fayter D, Corbett M, Heirs M, Fox D, Eastwood A. A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett's oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin. Health Technol Assess 2010 Jul;14(37):1-288 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20663420.
  3. 3.0 3.1 Sánchez A, Reza M, Blasco JA, Callejo D. Effectiveness, safety, and cost-effectiveness of photodynamic therapy in Barrett's esophagus: a systematic review. Dis Esophagus 2010 Nov;23(8):633-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20545970.
  4. 4.0 4.1 4.2 Li YM, Li L, Yu CH, Liu YS, Xu CF. A systematic review and meta-analysis of the treatment for Barrett's esophagus. Dig Dis Sci 2008 Nov;53(11):2837-46 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18427992.
  5. 5.0 5.1 Hage M, Siersema PD, van Dekken H, Steyerberg EW, Haringsma J, van de Vrie W, et al. 5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett's oesophagus: a randomised trial. Gut 2004 Jun;53(6):785-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15138203.
  6. 6.0 6.1 6.2 Kelty CJ, Ackroyd R, Brown NJ, Stephenson TJ, Stoddard CJ, Reed MW. Endoscopic ablation of Barrett's oesophagus: a randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation. Aliment Pharmacol Ther 2004 Dec;20(11-12):1289-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15606390.
  7. 7.0 7.1 Ackroyd R, Tam W, Schoeman M, Devitt PG, Watson DI. Prospective randomized controlled trial of argon plasma coagulation ablation vs. endoscopic surveillance of patients with Barrett's esophagus after antireflux surgery. Gastrointest Endosc 2004 Jan;59(1):1-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14722539.
  8. 8.0 8.1 Bright T, Watson DI, Tam W, Game PA, Astill D, Ackroyd R, et al. Randomized trial of argon plasma coagulation versus endoscopic surveillance for barrett esophagus after antireflux surgery: late results. Ann Surg 2007 Dec;246(6):1016-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18043104.
  9. 9.0 9.1 Bright T, Watson DI, Tam W, Game PA, Ackroyd R, Devitt PG, et al. Prospective randomized trial of argon plasma coagulation ablation versus endoscopic surveillance of Barrett's esophagus in patients treated with antisecretory medication. Dig Dis Sci 2009 Dec;54(12):2606-11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19101798.
  10. Zhang L, Dong L, Liu J, Lu X, Zhang J. Endoscopic ablation of Barrett's esophagus using the second generation argon plasma coagulation: a prospective randomized controlled trail. JNMU 2009;23(3):183-188.
  11. 11.0 11.1 Sie C, Bright T, Schoeman M, Game P, Tam W, Devitt P, et al. Argon plasma coagulation ablation versus endoscopic surveillance of Barrett's esophagus: late outcomes from two randomized trials. Endoscopy 2013 Sep 9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24019134.
  12. 12.0 12.1 12.2 Dulai GS, Jensen DM, Cortina G, Fontana L, Ippoliti A. Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus. Gastrointest Endosc 2005 Feb;61(2):232-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15729231.
  13. 13.0 13.1 Sharma P, Wani S, Weston AP, Bansal A, Hall M, Mathur S, et al. A randomised controlled trial of ablation of Barrett's oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results. Gut 2006 Sep;55(9):1233-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16905695.

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Appendices


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